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Trends in Medicare Reimbursement for Orthopedic Procedures: 2000 to 2016. Understanding trends in reimbursement is critical to the financial sustainability of orthopedic practices. Little research has examined physician fee trends over time for orthopedic procedures. This study evaluated trends in Medicare reimbursements for orthopedic surgical procedures. The Medicare Physician Fee Schedule was examined for Current Procedural Terminology code values for the most common orthopedic and nonorthopedic procedures between 2000 and 2016. Prices were adjusted for inflation to 2016-dollar values. To assess mean growth rate for each procedure and subspecialty, compound annual growth rates were calculated. Year-to-year dollar amount changes were calculated for each procedure and subspecialty. Reimbursement trends for individual procedures and across subspecialties were compared. Between 2000 and 2016, annual reimbursements decreased for all orthopedic procedures examined except removal of orthopedic implant. The orthopedic procedures with the greatest mean annual decreases in reimbursement were shoulder arthroscopy/decompression, total knee replacement, and total hip replacement. The orthopedic procedures with the least annual reimbursement decreases were carpal tunnel release and repair of ankle fracture. Rate of Medicare procedure reimbursement change varied between subspecialties. Trauma had the smallest decrease in annual change compared with spine, sports, and hand. Annual reimbursement decreased at a significantly greater rate for adult reconstruction procedures than for any of the other subspecialties. These findings indicate that reimbursement for procedures has steadily decreased, with the most rapid decrease seen in adult reconstruction. [Orthopedics. 2018; 41(2):95-102.].
{ "pile_set_name": "PubMed Abstracts" }
CHA helps Jo resolve issues with her insurance Jo Young is an actress living in Manhattan. A few years ago she enrolled in Medicaid, and has continued to recertify each year through the NYSOH Marketplace. Shortly after undergoing surgery, she tried to make an appointment at her primary care doctor for monitoring, but the office informed her that her Medicaid had been discontinued. Jo was shocked and extremely worried, as she needed regular care and follow-ups, but couldn’t afford those services without insurance. After going many months without medical care, Jo decided to seek assistance from Community Health Advocates. A CHA Advocate at the Community Service Society made several calls and discovered that Jo’s enrollment in a food assistance program had been mistaken as a duplicate application in the Medicaid system, consequently overriding Jo’s eligibility status. The Advocate helped Jo get this mistake fixed, and her Medicaid was reinstated. “If it weren't for the dedicated Community Health Advocates (CHA) team, I might still be without medical care.” Now Jo does not have to worry about accessing the lifesaving care she needs, and can focus on acting and staying healthy. “[CHA’s] dedication and persistence paid off, and I'm happy to say I now have excellent, consistent coverage. I owe it all to my friends at CHA!” “Sometimes you simply need a helping hand, and CHA certainly held my hand along my arduous journey through the healthcare world.” -- Jo
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François Isaac de Rivaz François Isaac de Rivaz (Paris, December 19, 1752 – Sion, July 30, 1828) was an inventor and a politician. He invented a hydrogen-powered internal combustion engine with electric ignition and described it in a French patent published in 1807. In 1808 he fitted it into a primitive working vehicle – "the world's first internal combustion powered automobile". Biography Isaac was born in Paris to a family from Valais. In 1763 the family settled in Moûtiers in Savoy (Kingdom of Sardinia). The last two boys, Anne Joseph and Isaac, came to settle in St. Gingolph in Valais. It is not known at which schools he studied, but he became fluent in Latin plus mastering mathematics and geometry, whilst continuing his study of mechanics throughout his life. He qualified as both a surveyor and notary and worked for the state of Valais. Isaac had many interests plus an intuitive and extremely curious mind which was driven by the demon of discovery. His experimental work was overflowing. He experimented with steam-powered vehicles in the late 18th century. He also studied the ignition of combustible gases. Internal combustion engine After retirement from the Army, living in Switzerland, he invented a primitive internal combustion engine which he constructed in 1807. It was powered by a mixture of hydrogen and oxygen manually ignited by electric spark, but the engine neither involved the in-cylinder compression, the crank, nor the connecting rod. A year later, Isaac built an early automobile for his new engine to power. His engine was never commercially successful. Alternative claims for internal combustion engines Coincidentally, in 1807 Nicéphore Niépce installed his 'moss, coal-dust and resin'-fueled Pyréolophore internal combustion engine in a boat and powered up the river Saone in France to be granted a patent by the Emperor Napoleon Bonaparte. The discrete, virtually simultaneous, implementations of these two designs of internal combustion in different modes of transport means that the de Rivaz engine can be correctly described as "the worlds first use of an internal combustion engine in an auto-mobile (in 1808)", whilst the "Pyréolophore (in 1807) was the world's first use of an internal combustion engine in a ship". Although de Rivaz's early work is credited as the first use of the internal combustion engine in an automobile, the further development and mass production of the invention never truly began until the late nineteenth century. In 1824, the French physicist Nicolas Léonard Sadi Carnot scientifically established the thermodynamic theory of idealized heat engines. This highlighted the shortcoming of these pioneering designs, whereby they needed a compression mechanism to increase the difference between the upper and lower working temperatures and potentially unlock sufficient power and efficiency. Gasoline was not used for internal combustion engines until 1870 when carburetors were invented to convert non-combustible liquid fuels into a combustible gaseous mixture form. See also De Rivaz engine Timeline of transportation technology Timeline of hydrogen technologies History of the internal combustion engine Pyréolophore Nicéphore Niépce References External links 1807 Francois Isaac de Rivaz - internal combustion engine Category:1752 births Category:1828 deaths Category:People associated with the internal combustion engine
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The present invention relates to a pneumatic tire whose tread portion is provided with sipes, more particularly to a design of a pair of sipes capable of preventing cracks at the bottoms of the sipes and improving demolding of the vulcanization mold with siping blades. Pneumatic tires are often provided in the tread portion with sipes in order to adjust the rigidity of ground contacting tread elements such as block, rib and the like, or increase edge effect for improving the traction performance and braking performance on icy roads for example. If such sipped tire receives a force to open the sipes during rolling and as a result stress concentrates at the bottoms of the sipes, there is a possibility that cracks occur at the bottoms of the sipes. In Japanese Patent Application Publication No. H3(1991)-007604, in order to prevent cracks, a sipe (a) is provided at the bottom with a circular cross sectional shape (c) whose diameter is larger the thickness (w) of the sipe as shown in FIG. 5(a). If such sipes (a) are formed at small intervals by the use of siping blades (g) provided on the inside of a vulcanizing mold, then it becomes hard to demold or the rubber (ba) between the siping blades (g) is torn off by the siping blades (g) when demolding as shown in FIG. 5(b).
{ "pile_set_name": "USPTO Backgrounds" }
It has all the benefits of Unlimited (talk, text, data) and literally more! One of those extras is streaming on us. With AT&T Unlimited &MoreSM plans you can stream 30+ live channels with unlimited access to more than 15,000 titles, live and on demand, through the WatchTV app for no charge! For pricing, visit our package page. Check out what the AT&T Newsroom has to say about our new unlimited plans! ChrisZ, AT&T Community Specialist AT&T Customer Care Need help with an account specific question? Post a new question here on the forums by clicking the "Ask a Question" button.For additional support, please visit us at our AT&T services hub.Follow us on: Twitter @ATTCares and @DIRECTVService Re: AT&T Unlimited & More Plans – Get The Scoop! Need help with an account specific question? Post a new question here on the forums by clicking the "Ask a Question" button.For additional support, please visit us at our AT&T services hub.Follow us on: Twitter @ATTCares and @DIRECTVService *I am an AT&T employee, and the postings on this site are my own and don't necessarily represent AT&T's position, strategies or opinions. Re: AT&T Unlimited & More Plans – Get The Scoop! It's a nice price increase also for folks that have unlimited choice and unlimited plus.... Just so you are all aware... Pic is with 6 lines and 2 watches with military discount..... Award for Community Excellence 2019 Achiever**The views and opinions expressed on this forum are purely my own. Any product claim, statistic, quote, or other representation about a product or service should be verified with the manufacturer, provider, or party. Re: AT&T Unlimited & More Plans – Get The Scoop! Can you get the unlimited without all the extra entertainment! Don't need extra entertainment services. Currently have 30 GB plan for 3 iPhones but the young men tend to use all the data and tend to be almost over this month and its not even 28th which is the last day of the billing for us. So debating on changing as there is no 30 GB plan like we were offer long time ago as we have a family shared plan. We have roll over data which only last for 1 billing but that doesn't always help. So looking for another option worried if I change in-between billing cycle will have all these charges added to my bill. Plus I don't want them to have option to use these options with extra enterntainment can it be turn off by the main person on the account? Re: AT&T Unlimited & More Plans – Get The Scoop! Can you get the unlimited without all the extra entertainment! Don't need extra entertainment services. Call 611 and ask for retention and see if they can still offer you the unlimited plans. I think it's $5 cheaper (after the $10 autopay discount) and you can also ask AT&T for the additional $10 unlimited loyalty discount. Let us know how that works, please! So looking for another option worried if I change in-between billing cycle will have all these charges added to my bill. Plus I don't want them to have option to use these options with extra enterntainment can it be turn off by the main person on the account? The entertainment only works if enabled by the main line on the account. Rember the Golden Rule: Treat others how you would like to be treated. Just because my answer does not solve your issue (or agree with you), it may still be correct information... Stating a fact about how something works, is NOT taking sides, it's just stating a fact... Information provided might not be for "you" only, it might be clarification for other community members. This is the public AT&T Community Forum (not AT&T support), please do not post personal info. When provided an answer, please click "Accept solution" which helps other people to find an answer more quickly. The (very) fine print - This footer is at the bottom of all my posts, its particulars may, or may not, apply to you & your post. Award for Community Excellence 2019 Achiever**The views and opinions expressed on this forum are purely my own. Any product claim, statistic, quote, or other representation about a product or service should be verified with the manufacturer, provider, or party. Re: AT&T Unlimited & More Plans – Get The Scoop! Auto pay is not included in the bottom number. Award for Community Excellence 2019 Achiever**The views and opinions expressed on this forum are purely my own. Any product claim, statistic, quote, or other representation about a product or service should be verified with the manufacturer, provider, or party. Re: AT&T Unlimited & More Plans – Get The Scoop! Is this a bait and switch? Why did it change once I changed the plan? It goes from 80 to 90 even though it clearly states both plans are the same price! That's NOT what 'bait and switch' means. If they're lying about the price, it's just called "lying" (not 'bait and switch') Everywhere it says $80 it says including 'autopay/paperless discount'. This image that YOU uploaded says $90 and then right under it says 'autopay/paperless discount is pending'. Rember the Golden Rule: Treat others how you would like to be treated. Just because my answer does not solve your issue (or agree with you), it may still be correct information... Stating a fact about how something works, is NOT taking sides, it's just stating a fact... Information provided might not be for "you" only, it might be clarification for other community members. This is the public AT&T Community Forum (not AT&T support), please do not post personal info. When provided an answer, please click "Accept solution" which helps other people to find an answer more quickly. The (very) fine print - This footer is at the bottom of all my posts, its particulars may, or may not, apply to you & your post. Award for Community Excellence 2019 Achiever**The views and opinions expressed on this forum are purely my own. Any product claim, statistic, quote, or other representation about a product or service should be verified with the manufacturer, provider, or party. Re: AT&T Unlimited & More Plans – Get The Scoop! What's the point of this if we already have television service through AT&T/DirecTV? Do we not have access to our television service for free through an app already? Why do the mobile share plans have to be so expensive yet BARELY cheaper so you can practically force the upgrade? Why does AT&T feel such a need to screw over so many loyal customers just to make a buck? If I can't access my television through my smart tv's without more boxes, I'm about to take advantage of cancelling my service before the initial period is up and, yet again, AT&T can kiss my bum. I hated you when I sold this mess door to door. Love the service itself, but despise your sheisty ways of treating your customers. It's really and truly just SAD. Re: AT&T Unlimited & More Plans – Get The Scoop! AND- WHY CAN'T THERE JUST BE REGULAR OLE UNLIMITED WITHOUT ALL THIS? Was going to sign a wireless contract, but until you can do better, nada. You will more than likely be losing this customer regardless as soon as I hear some answers to my inquiry. I was here in the forum to understand bill credits, and I think I've jarred some sense back into my head with just perusing forum discussions. Shame, shame. Re: AT&T Unlimited & More Plans – Get The Scoop! I am afraid to make any more changes. In the beginning I had family share plan but in order to get the direct tv doesn't count against your data I had to switch to what I have now which is some kind of unlimited plan. Not 6 ,months after I made the change guess what..or it doesn't matter what kind of plan you have now you can watch direct through the app and it will, not count against your data. Well all fine and good but I can't switch back to what I had now. I have been with this company since the days of the Motorola bag phones and Cingular/bellsouth mobility. From what I can tell the company does things like this to get you to move from a plan that may be better for you to a plan that is more better for the company and then wham its too late to go back. Re: AT&T Unlimited & More Plans – Get The Scoop! on this new plan can you have an additional device added like a tablet for the same $10 month I'm paying now? Probably not. I have read and read the fine print till my eyes hurt and I can't fine anything about it except the company does offer a separate plan for like 30 plus dollars a month so there you go again. I loose for $10 a month tablet and have to play an additional sum just to keep that and its for less data. Re: AT&T Unlimited & More Plans – Get The Scoop! on this new plan can you have an additional device added like a tablet for the same $10 month I'm paying now? Probably not. I have read and read the fine print till my eyes hurt and I can't fine anything about it except the company does offer a separate plan for like 30 plus dollars a month so there you go again. I loose for $10 a month tablet and have to play an additional sum just to keep that and its for less data. THREE options: $20 for a tablet to have unlimited. $10 for a tablet to have 1GB. FREE to share 15GB from your phone to your tablet. Rember the Golden Rule: Treat others how you would like to be treated. Just because my answer does not solve your issue (or agree with you), it may still be correct information... Stating a fact about how something works, is NOT taking sides, it's just stating a fact... Information provided might not be for "you" only, it might be clarification for other community members. This is the public AT&T Community Forum (not AT&T support), please do not post personal info. When provided an answer, please click "Accept solution" which helps other people to find an answer more quickly. The (very) fine print - This footer is at the bottom of all my posts, its particulars may, or may not, apply to you & your post. Award for Community Excellence 2019 Achiever**The views and opinions expressed on this forum are purely my own. Any product claim, statistic, quote, or other representation about a product or service should be verified with the manufacturer, provider, or party. Re: AT&T Unlimited & More Plans – Get The Scoop! I am afraid to make any more changes. In the beginning I had family share plan but in order to get the direct tv doesn't count against your data I had to switch to what I have now which is some kind of unlimited plan. Who told you that? From the day ATT bought Direct TV, which is before they offered an unlimited data plan again, DTV app use was sponsored data. (DTV acquired in 2014, Unlimited + TV plan in 2016). Not 6 ,months after I made the change guess what..or it doesn't matter what kind of plan you have now you can watch direct through the app and it will, not count against your data. Well all fine and good but I can't switch back to what I had now. I have been with this company since the days of the Motorola bag phones and Cingular/bellsouth mobility. From what I can tell the company does things like this to get you to move from a plan that may be better for you to a plan that is more better for the company and then wham its too late to go back. You can switch to a shared plan. The 20 gig plan is $100 plus $20 for phones, $10 tablets. No overage charges. (The following is included after all posts to save typing) I don’t work for AT&T. My replies are based on experience and reading content available on the website. Our answers are honest, but not always appreciated. If you posted personal information, please edit and remove. Award for Community Excellence 2019 Achiever**The views and opinions expressed on this forum are purely my own. Any product claim, statistic, quote, or other representation about a product or service should be verified with the manufacturer, provider, or party.
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The Boy Wonder won’t be flying into primetime after all. The CW and Warner Bros. TV have been forced to scrap their plans for “The Graysons.” Show, which had been given a put pilot commitment, was set to revolve around Batman sidekick Robin in his pre-Caped Crusader days. Decision to yank the project came from Warner Bros. Pictures Group prexy Jeff Robinov, who initially gave his blessing but changed his mind in recent days. “Warner Bros. TV never had 100% clearance,” said one exec familiar with the project. The CW had been counting on “The Graysons” to fill the void left by the likely series end of “Smallville.” Like “Smallville,” “The Graysons” is a superhero origins story. Show was developed to revolve around the world of Dick “DJ” Grayson before taking on the iconic Robin identity. Project was to be the latest DC Comics franchise to be mined for the smallscreen by Warner Bros. TV. “Smallville” exec producers Kelly Souders and Brian Peterson were set to write and exec produce, while Wonderland Sound and Vision’s McG and Peter Johnson were also aboard to exec produce. According to studio insiders, Robinov has decreed that Warner Bros. “rethink its DC Comics strategy” and as a result didn’t want to do anything big with a DC franchise at the moment — at least when it came to “Graysons.” “The studio has opted not to go forward with the development of ‘The Graysons’ at this time as the concept doesn’t fit the current strategy for the Batman franchise,” the studio said in a statement. “Warner Bros. Television is currently working on several replacement options for the CW.” It’s understood that “The Dark Knight” helmer Christopher Nolan never signed off on the TV show; one insider said the helmer was uncomfortable with having a TV show related to the Batman franchise on the air. But according to the studio, the decision to scrap the show rested solely on Robinov and not Nolan. Others wondered whether Warner Bros. got nervous over the idea of having a both an active Batman TV series and film series at the same time. “Smallville” and, before that, “Lois & Clark,” were launched during a lengthy hiatus from the bigscreen for Superman. Some believe 2006’s “Superman Returns” was hurt at the box office because of the simultaneous TV show. A script had not yet been written for “The Graysons,” which was still in early stages of development. Word of “The Graysons” first emerged last month (Daily Variety, Oct. 1) — prematurely, in hindsight. The one-hour “Graysons” was to be set in modern times and focus on young DJ as he faced challenges involving first loves, young rivals and his family — a famous juggling act — as he grew up. (In Batman lore, Grayson was part of a family act called “The Flying Graysons” and orphaned after a gangster had his parents killed.) Insiders said Warner Bros. TV is now scanning its library for other potential franchises to develop for the CW. The netlet is already kicking the tires on other franchises for next year, including a revival of CBS Paramount’s “Melrose Place.” Coincidentally, a new animated Batman series, “Batman: The Brave and the Bold,” bows on Cartoon Network next Friday.
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Q: Can "mon bon" refer only to "my friend," or could it mean "my muse" or "my angel"? Need to understand if phrase "mon bon" means "mon bon ami" or can suggest other meanings such as "muse" or "guardian angel." A: I think mon bon is more like my friend, but with quite a bit of condescension. It is quite dated too. I don't think anybody uses that today, unless there is a resurgence in popular speech.
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Cannabinergic pain medicine: a concise clinical primer and survey of randomized-controlled trial results. This article attempts to cover pragmatic clinical considerations involved in the use of cannabinergic medicines in pain practice, including geographical and historical considerations, pharmacokinetics, pharmacodynamics, adverse effects, drug interactions, indications, and contraindications. Topics include molecular considerations such as the 10-fold greater abundance of cannabinoid type 1 receptors compared to µ-opioid receptors in the central nervous system and anatomic distributions of cannabinoid receptors in pain circuits. The article uses a narrative review methodology drawing from authoritative textbooks and journals of cannabinoid medicine, Food and Drug Administration-approved cannabinoid drug labels, and current and historical pain medicine literature to address core clinical considerations. To survey the current evidence base for pain management with cannabinergic medicines, a targeted PubMed search was performed to survey the percentage of positive and negative published randomized-controlled trial (RCT) results with this class of pain medicines, using appropriate search limit parameters and the keyword search string "cannabinoid OR cannabis-based AND pain." Of the 56 hits generated, 38 published RCTs met the survey criteria. Of these, 71% (27) concluded that cannabinoids had empirically demonstrable and statistically significant pain-relieving effects, whereas 29% (11) did not. Cannabis and other cannabinergic medicines' efficacies for relieving pain have been studied in RCTs, most of which have demonstrated a beneficial effect for this indication, although most trials are short-term. Adverse effects are generally nonserious and well tolerated. Incorporating cannabinergic medicine topics into pain medicine education seems warranted and continuing clinical research and empiric treatment trials are appropriate.
{ "pile_set_name": "PubMed Abstracts" }
Incisor disocclusion in rats affects mandibular condylar cartilage at the cellular level. The effect of altered occlusion on the mandibular condylar cartilage remains unclear. This study investigated the effect of unilateral incisor disocclusion on cartilage thickness, on mitotic activity and on chondrocytes maturation and differentiation in the mandibular condylar cartilage of rats. The upper and lower left incisors were trimmed 2mm every second day in five rats. In other five rats, the incisor occlusion was not altered. Condylar tissues from both sides of each mandible were processed and stained for Herovici's stain and immunohistochemistry for bromodeoxyuridine (BrdU), transforming growth factor-beta1 (TGF-beta1), alkaline phosphatase (ALP) and osteocalcin (OCN). Measurements of cartilage thickness and the numbers of immunopositive cells for each antibody were analysed by one-way analysis of variance (ANOVA). No significant differences were observed in cartilage thickness after 7 days of unilateral incisor disocclusion. However, the numbers of immunopositive cells for BrdU as a marker of DNA synthesising cells, TGF-beta1 as a marker of chondrocytes differentiation, and ALP and OCN as markers of chondrocytes maturation, were significant higher in the cartilage cells on both sides when incisor occlusion was unilaterally altered. Interestingly, alkaline phosphatase was highly expressed on the condylar side of incisor disocclusion, whereas osteocalcin was highly expressed on the side opposite to the incisor disocclusion. It is demonstrated that after 7 days, unilateral incisor disocclusion affects the mandibular condylar cartilage at the cellular level by increasing the mitotic activity and by accelerating chondrocytes maturation. Chondrocytes maturation appears more accelerated on the side opposite to incisor disocclusion.
{ "pile_set_name": "PubMed Abstracts" }
The menarche experience in twenty-three foreign countries. Ninety-five women (aged 18-26) from 23 countries were interviewed regarding their first menstrual experience. Among the areas discussed were (1) their preparation for menarche, (2) messages from others at the time of menarche, and (3) their own emotional reactions to the first period. Although the mother, as might be expected, was the main source of information, almost one-third of the girls received no maternal assistance prior to menarche. The chief reaction of others to a girl's first period centered on help with the hygienic routine. Only in Iran was a non-hygienic response more common--reassurance of the normality of the event. The emotional reactions of the women themselves differed widely. Asians most often reported feeling "embarrassed" and "surprised." In contrast, Iranians most frequently mentioned feeling "more grown up". The discussion includes a comparison of the international women's descriptions of their menarche with data available on American samples. Finally, the paper concludes with an analysis of the importance of a culture's response to the menarcheal female.
{ "pile_set_name": "PubMed Abstracts" }
Fernhill House First Birthday !! Tuesday 24th April, 2018 Today we have been celebrating our first birthday at Fernhill House. It was Fish n chips and cake all round for residents and staff, followed by an afternoon of entertainment by Reza Farrell who sang to us some classic 40's and 50's song's. We had a brilliant time!!
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[Surgical treatment of coronary artery-pulmonary artery fistula]. We experienced 4 cases of left coronary artery-pulmonary artery fistula. Two cases had small fistulas associated with atherosclerotic coronary lesions, and the other 2 had large fistulas with aneurysmal enlargement. In the former 2 cases, ligation of the fistulas and closure of the opening of fistula into the pulmonary artery through pulmonary arteriotomy were performed together with coronary artery bypass grafting and left ventricular aneurysmectomy. In one of the latter 2 cases, the fistula arising from the anterior descending branch was ligated and the opening of fistula draining into the pulmonary artery was closed through pulmonary arteriotomy. In another case, both openings of the fistula into the anterior descending branch and the pulmonary artery were closed from inside through incision of the dilated fistula. In all 4 cases, operations were performed using cardiopulmonary bypass and retrograde coronary perfusion, which could afford good heart protection even in cases with coronary lesions and coronary steal phenomenon. All cases went an uneventful postoperative course. Postoperative angiograms showed disappearance of the fistulas in 3 cases. In one case, however, residual fistula was found because a fine fistula might be overlooked. In such a case with complicated fistulas with aneurysmal enlargement, fistulas should be examined carefully through incision of the enlarged anomalous vessels. In this paper, diagnosis, operative indication and treatment for coronary artery-pulmonary artery fistula were discussed.
{ "pile_set_name": "PubMed Abstracts" }
What makes rape a special kind of violence? It’s not the physical damage, which can be very minimal; it’s the emotional damage, which can be catastrophic. Rape makes you afraid; it taints your trust in the world and twists how you see it. It drives you into a prison of fear. But all other violence does that as well. What’s truly special about rape is simple. It takes a bludgeon to your ability to bond with others in the most intimate way. Rape robs you of your ability to see innocence. “Get rid of men and you get rid of rape.” The sexual exploitation of women by men is the greatest taboo in our society; there is nothing more stigmatized than being a rapist of women. Rape is a call to action; today it’s dressed up in new terms but it still harkens back to that primitive urge to protect female sexuality from foreign interlopers. Modern gynocentrists did not invent rape hysteria; they inherited it and they are using it the way everyone throughout history has—as a tool to grind away at things they don’t like. For the woman on the street, rape hysteria is shoved down her throat over and over till she vomits it up without thinking, all over herself and her life. It seeps into every interaction, every step she takes into the outer world. ‘Is this man going to rape me? All men are guilty! I’m never safe and it’s their fault!’ That’s where rape hysteria wants all women to be. Frightened, helpless… impotent. Calling upon a higher authority to save them. And, of course, robbing the men around them of their innocence. “All men are responsible for rape culture.” But rape isn’t something that happens to women; it isn’t something done to women by men. It’s a human problem and it’s a human problem that does not know gender. More men are raped in prison a year than women in the general population. More boys in juvenile facilities are raped than girls. And they are raped by women. There are surveys that show just as many men are raped in romantic relationships—date-raped—as women. That leaves stranger rape; 26% of all non-institutional rape. It may well be that most stranger-rapists are men; but it does not follow that a vast majority of their victims are women. An argument can be made that men under-report; and studies have shown that rapists who are heterosexual in their consenting relationships will rape based on vulnerability not sex. Statically women are not more vulnerable to rape. And there is something else; in reading about the victimization of men by women, another story emerges. Female potency. Male victims, teens and adults, are changed by having been raped by a woman—they are suicidal, addicted, dysfunctional, unhinged, helpless, hurting. In the background of many male rapists of adult women is sexual abuse done to them by women. The vagina employed as a weapon can carve and twist a man so badly he defies society’s most fundamental taboo—male on female rape. The vagina is a weapon every bit as potent as a penis. It can steal innocence. “All sex is rape.” A child does not see innocence. To a child the world is good and bad; the good pleases the child, the bad displeases her. The world is made of good and bad people. Good people benefit the child; bad people do not. Innocence, to a child, if it is seen is seen as weakness and a threat. Someone else’s weakness threatens the child’s absolute claim to the attention and effort of adults. In the child’s calculus need equals worth and other’s needs lessen the child’s worth. The only eyes that can see innocence are those that know they can take it away. Or protect it. Innocence is inspiration. A call to protect and provide, to be strong. It may be passive but it is powerful. It’s why someone will brave flames—literal or metaphorical—to save another. Like children, many women expect men to fill them with passion. But passion only exists in those who can bear the sight of innocence. “The personal is political.” Before I started to read about men’s rights I was, like every other woman, bound by rape hysteria. Men in my eyes bore their burden of guilt and I, in turn, bore my burden of fear. But I was lucky. I stumbled upon the men’s rights movement and saw things—statistics, studies—they pulled up from the depths of our society’s subconscious—things that would silently slip down into the deep if it weren’t for them. All the evidence I’ve seen against rape hysteria is not good enough for those who profit from keeping women in a prison of fear; but it’s good enough for me to question my obligation to stay. I realized women have sexual potency. And if women are equally responsible for rape, then they have an equal responsibility to be responsible. Because women can take away men’s—and boy’s—innocence. There was no need for men to carry a burden of guilt; nor was there a need for me to carry a burden of fear. A weight lifted from me in that moment; a weight I never knew I carried till it was gone. Before I had always seen my husband—and every other man—as either a good man or a bad man; but never innocent. His actions were always deliberate, if he did me harm he was a villain with the blackest heart; if he did me good, he was a knight-in-shining armor. After, he became innocent. “The fear of rape limits women’s potential.” Women infected by rape hysteria will meet bad men, creepy men, evil men. And they’ll meet good men, real men, strong men. But they will never meet an innocent man. They are poorer for it. My name is Typhonblue and I am a survivor of rape hysteria.
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Give your illustrations an old etched or engraved appearance with my new collection of 30 free brushes for Adobe Illustrator. These brushes feature a variety of hand-drawn line patterns in horizontal, vertical, diagonal and cross-hatched orientations that can be used to apply shading to your digital drawings. After being scanned from hand-made pen strokes, they were then processed into Illustrator brushes that seamlessly repeat along paths of any length without stretching or deforming. How to use the vintage shading brushes Open the brushes file into Illustrator by choosing ‘Load Brushes’ from the Brushes panel menu. Each brush can then be applied to a path that has been drawn with the Brush, Pencil, Line or Pen tool. To change the scale of the brush, alter the stroke weight to increase or decrease its size. The brush stroke will likely extend beyond the desired shading area. One technique to trim it to size is by drawing a temporary shape and set it as a clipping mask to make the excess portions invisible. An alternative masking technique is to add an Opacity Mask to the path, then paint over the unwanted areas with the Blob brush (or a black-filled shape) to hide the excess. Download My Free Vintage Shading Brushes
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Q: Get image content from httpResponse in Android Am trying to get a image from a http response, but am failing to convert the stream to bitmap. Please let me know, what am i missing here. FYI - the image content is received as raw binary & its a jpeg image. Procedure followed: Make HttpRequest. In response check for 200 -> get the httpentity content. convert the stream to bitmap using BitMap factory. Set the bitmap to imageview Doing this in postExecute of the AsyncTask HttpClient httpclient = new DefaultHttpClient(); HttpGet httpget = new HttpGet(endpoint); // Adding Headers .. // Execute the request HttpResponse response; try { response = httpclient.execute(httpget); if (response.getStatusLine().getStatusCode() == 200) { // Get hold of the response entity HttpEntity entity = response.getEntity(); if (entity != null) { InputStream instream = entity.getContent(); return instream; // instream.close(); } } } Doing this in postExecute of the AsyncTask if (null != instream) { Bitmap bm = BitmapFactory.decodeStream(instream); if(null == bm){ Toast toast = Toast.makeText(getApplicationContext(), "Bitmap is NULL", Toast.LENGTH_SHORT); toast.show(); } ImageView view = (ImageView) findViewById(R.id.picture_frame); view.setImageBitmap(bm); } Thanks in Advance. A: Finally found the answer for this. below is the snippet - might help for the newbees working with http responses. HttpClient httpclient = new DefaultHttpClient(); HttpGet httpget = new HttpGet(endpoint); // Adding Headers .. // Execute the request HttpResponse response; try { response = httpclient.execute(httpget); if (response.getStatusLine().getStatusCode() == 200) { // Get hold of the response entity HttpEntity entity = response.getEntity(); if (entity != null) { InputStream instream = entity.getContent(); String path = "/storage/emulated/0/YOURAPPFOLDER/FILENAME.EXTENSION"; FileOutputStream output = new FileOutputStream(path); int bufferSize = 1024; byte[] buffer = new byte[bufferSize]; int len = 0; while ((len = instream.read(buffer)) != -1) { output.write(buffer, 0, len); } output.close(); } Instead of saving the file to disk, we can have the contents in the bytearray and get the bitmap from that. ByteArrayOutputStream baos = new ByteArrayOutputStream(); int bufferSize = 1024; byte[] buffer = new byte[bufferSize]; int len = 0; try { // instream is content got from httpentity.getContent() while ((len = instream.read(buffer)) != -1) { baos.write(buffer, 0, len); } baos.close(); } catch (IOException e) { e.printStackTrace(); } byte[] b = baos.toByteArray(); Bitmap bmp = BitmapFactory.decodeByteArray(b, 0, b.length); ImageView imageView = (ImageView)findViewById(R.id.picture_frame); imageView.setImageBitmap(bmp); FYI - In android fileoutput stream writing to local disk have to be done in non UI thread(have used async task in my case & that part is not added here). Thanks ..
{ "pile_set_name": "StackExchange" }
[Mini-Series]: Lucio Laugelli – “Su Marte non c’è il Mare” “Su Marte non c’è il mare “is an independent mini-series, directed by Lucio Laugelli. It is about the suburbs life in a Northern Italy city (Alessandria and Asti area) and, at the same time, a shocking story that destabilizes lives of the main characters. 15 minutes-4 episodes, each filmed with the contribution of Cral Foundation. Soundtrack features the extraordinary contribution of Turin-based band Perturbazione. The Story: A thirty-years old man, with a job he doesn’t like, rents illegally the house left to him by his grandfatherto a particular customer that only wants it on Friday night, but it pays very well. From that timeit’s all for the best, but he will discover soon that something doesn’t square with the situation.
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package edas //Licensed under the Apache License, Version 2.0 (the "License"); //you may not use this file except in compliance with the License. //You may obtain a copy of the License at // //http://www.apache.org/licenses/LICENSE-2.0 // //Unless required by applicable law or agreed to in writing, software //distributed under the License is distributed on an "AS IS" BASIS, //WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. //See the License for the specific language governing permissions and //limitations under the License. // // Code generated by Alibaba Cloud SDK Code Generator. // Changes may cause incorrect behavior and will be lost if the code is regenerated. // ResultInListRootStacks is a nested struct in edas response type ResultInListRootStacks struct { RootStack []RootStack `json:"RootStack" xml:"RootStack"` }
{ "pile_set_name": "Github" }
<?php /** * Cache of file objects, wrapping some RepoGroup functions to avoid redundant * queries. Loosely inspired by the LinkCache / LinkBatch classes for titles. * * ISSUE: Merge with RepoGroup? * * @ingroup FileRepo */ class FileCache { var $repoGroup; var $cache = array(), $notFound = array(); protected static $instance; /** * Get a FileCache instance. Typically, only one instance of FileCache * is needed in a MediaWiki invocation. */ static function singleton() { if ( self::$instance ) { return self::$instance; } self::$instance = new FileCache( RepoGroup::singleton() ); return self::$instance; } /** * Destroy the singleton instance, so that a new one will be created next * time singleton() is called. */ static function destroySingleton() { self::$instance = null; } /** * Set the singleton instance to a given object */ static function setSingleton( $instance ) { self::$instance = $instance; } /** * Construct a group of file repositories. * @param RepoGroup $repoGroup */ function __construct( $repoGroup ) { $this->repoGroup = $repoGroup; } /** * Add some files to the cache. This is a fairly low-level function, * which most users should not need to call. Note that any existing * entries for the same keys will not be replaced. Call clearFiles() * first if you need that. * @param array $files array of File objects, indexed by DB key */ function addFiles( $files ) { wfDebug( "FileCache adding ".count( $files )." files\n" ); $this->cache += $files; } /** * Remove some files from the cache, so that their existence will be * rechecked. This is a fairly low-level function, which most users * should not need to call. * @param array $remove array indexed by DB keys to remove (the values are ignored) */ function clearFiles( $remove ) { wfDebug( "FileCache clearing data for ".count( $remove )." files\n" ); $this->cache = array_diff_keys( $this->cache, $remove ); $this->notFound = array_diff_keys( $this->notFound, $remove ); } /** * Mark some DB keys as nonexistent. This is a fairly low-level * function, which most users should not need to call. * @param array $dbkeys array of DB keys */ function markNotFound( $dbkeys ) { wfDebug( "FileCache marking ".count( $dbkeys )." files as not found\n" ); $this->notFound += array_fill_keys( $dbkeys, true ); } /** * Search the cache for a file. * @param mixed $title Title object or string * @return File object or false if it is not found * @todo Implement searching for old file versions(?) */ function findFile( $title ) { if( !( $title instanceof Title ) ) { $title = Title::makeTitleSafe( NS_FILE, $title ); } if( !$title ) { return false; // invalid title? } $dbkey = $title->getDBkey(); if( array_key_exists( $dbkey, $this->cache ) ) { wfDebug( "FileCache HIT for $dbkey\n" ); return $this->cache[$dbkey]; } if( array_key_exists( $dbkey, $this->notFound ) ) { wfDebug( "FileCache negative HIT for $dbkey\n" ); return false; } // Not in cache, fall back to a direct query $file = $this->repoGroup->findFile( $title ); if( $file ) { wfDebug( "FileCache MISS for $dbkey\n" ); $this->cache[$dbkey] = $file; } else { wfDebug( "FileCache negative MISS for $dbkey\n" ); $this->notFound[$dbkey] = true; } return $file; } /** * Search the cache for multiple files. * @param array $titles Title objects or strings to search for * @return array of File objects, indexed by DB key */ function findFiles( $titles ) { $titleObjs = array(); foreach ( $titles as $title ) { if ( !( $title instanceof Title ) ) { $title = Title::makeTitleSafe( NS_FILE, $title ); } if ( $title ) { $titleObjs[$title->getDBkey()] = $title; } } $result = array_intersect_key( $this->cache, $titleObjs ); $unsure = array_diff_key( $titleObjs, $result, $this->notFound ); if( $unsure ) { wfDebug( "FileCache MISS for ".count( $unsure )." files out of ".count( $titleObjs )."...\n" ); // XXX: We assume the array returned by findFiles() is // indexed by DBkey; this appears to be true, but should // be explicitly documented. $found = $this->repoGroup->findFiles( $unsure ); $result += $found; $this->addFiles( $found ); $this->markNotFound( array_keys( array_diff_key( $unsure, $found ) ) ); } wfDebug( "FileCache found ".count( $result )." files out of ".count( $titleObjs )."\n" ); return $result; } }
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Healthy Cake Batter Overnight Dessert Oats These Cake Batter Overnight Dessert Oats have all the flavor of cake, just in a healthier package. This easy overnight oats recipe is sweet and uber filling, yet sugar free, gluten free, dairy free, and vegan! Cake Batter for breakfast? Hell to the yes! While this may not look like a slice of cake, it sure tastes like one. Just close your eyes, shove a giant spoonful into your face, and enjoy. Every bite is sweet and buttery and vanilla-y, you’ll seriously question how it could be healthy. These Cake Batter Overnight Dessert Oats have all the flavor of cake, just in a healthier package. This easy overnight oats recipe is sweet and uber filling, yet sugar free, gluten free, dairy free, and vegan! In a bowl, stir together a splash of almond milk and the nut butter until completely smooth. Stir in the remaining milk and vanilla extract. Stir in the oats, sweetener, and salt. Cover and refrigerate overnight. Serve and enjoy in the morning along with natural rainbow sprinkles, sliced strawberries or bananas, mini chocolate chips, or spoons alone! Recipe Notes If you want super duper creamy oats with a hit of protein, add ¼ cup of Greek yogurt to the recipe. If you’re vegan, feel free to stir in 1-2 tablespoons of your favorite vegan vanilla protein powder plus an extra splash of almond milk. I don’t know about you, but the minute I wake up… no, the SECOND I wake up… the only thing that’s on my mind is food. WTF? (“Where’s The Food?”) Immediately after food, my brain switches over to coffee. WHERE’S THE COFFEE?!?! Does that sound like your morning routine too? If so, then I’m glad we’re in this together. This Cake Batter Oatmeal is our saving grace. Just mix together 5 ingredients, stick it in the fridge, go to bed, and BAM! Breakfast is all done and ready for you come morning time. All you gotta do is roll out of bed (or jump out, depending on how excited you are for this damn good brekky), open the fridge, and dig in with a spoon. Yep, you’re welcome. Imagine how much more awesome your mornings would be with Cake Batter Overnight Oats in it?!? Which would you rather have? An amazingly buttery and sweet slice of cake or a healthy breakfast? Why not both? Because you totally can with a bowl full of Cake Batter Overnight Oats! For real guys. I’m not lying. This tastes like cake. Now go. Go make a bowl of this for breakfast. I command you! 😉 . With love and good eats, . – Jess . Want to join the healthy dessert club? Subscribe to the newsletter and get decadent, yet healthy, treats sent straight to your inbox... FREE! Hey Jessica! I am a beginning bodybuilder/health-nut who has a reigning sweet tooth and I just want to thank you so much for making it so easy for me to stick to my lifestyle while truly enjoying it! while the other guys are eating bland chicken and rice for breakfast, I get cake batter oat meal! 😀 Plus I see results faster than most because im not tempted to cheat! I pray that the Lord continues to bless you and your work and that your chocolate cup flows over in abundance! ^_^ Kasey~ Kasey- Oh YAY I’m glad! That seriously made me SO happy to read that 😀 Cake Batter Oatmeal just makes life wayyy better 😉 Thank you so much for being so kind. I wish you all the best in your bodybuilding and competitions! -Jess I love cake batter flavored things. Unfortunately, they are usually filled with crap… and that’s definitely not what I am looking for. So I am sooo excited to find your healthier cake battery option, that’s for breakfast!! WINNNNNER! Your email address will not be published. Required fields are marked * Comment Name * Email * Website Save my name, email, and website in this browser for the next time I comment. Recipe Rating Welcome to Desserts With Benefits®! My name is Jessica and there’s a good chance I’m eating cake as we speak (healthy cake, of course)! Here at DWB, we use good-for-you ingredients to make balanced treats we can feel good about eating. (Read More ») Join the Healthy Dessert Recipe Club! Never miss a recipe, and get treated with some exclusive recipes and free goodies! Jessica’s Cookbooks! DIY Protein Bars: Easy, Healthy, Homemade No-Bake Treats That Are Packed With Protein is a collection of 48 ahhhmazing protein bar recipes! Print available on Amazon.com. PDF Download available on Etsy. . Naughty or Nice: The ULTIMATE Healthy Dessert Cookbook is a collection of 70 delicious, good-for-you recipes that’ll make you ask, “Is this naughty or is this nice?!” Print and Kindle available on Amazon.com. NEW! Baking Videos Desserts With Benefits® is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.
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Electrospinning collagen/chitosan/poly(L-lactic acid-co-ε-caprolactone) to form a vascular graft: mechanical and biological characterization. For blood vessel tissue engineering, an ideal vascular graft should possess excellent biocompatibility and mechanical properties. For this study, a elastic material of poly (L-lactic acid-co-ε-caprolactone) (P(LLA-CL)), collagen and chitosan blended scaffold at different ratios were fabricated by electrospinning. Upon fabrication, the scaffolds were evaluated to determine the tensile strength, burst pressure, and dynamic compliance. In addition, the contact angle and endothelial cell proliferation on the scaffolds were evaluated to demonstrate the structures potential to serve as a vascular prosthetic capable of in situ regeneration. The collagen/chitosan/P(LLA-CL) scaffold with the ratio of 20:5:75 reached the highest tensile strength with the value of 16.9 MPa, and it was elastic with strain at break values of ~112%, elastic modulus of 10.3 MPa. The burst pressure strength of the scaffold was greater than 3365 mmHg and compliance value was 0.7%/100 mmHg. Endothelial cells proliferation was significantly increased on the blended scaffolds versus the P(LLA-CL). Meanwhile, the endothelial cells were more adherent based on the increase in the degree of cell spreading on the surface of collagen/chitosan/P(LLA-CL) scaffolds. Such blended scaffold especially with the ratio of 20:5:75 thus has the potential for vascular graft applications.
{ "pile_set_name": "PubMed Abstracts" }
During the 18-day trial involving more than a dozen witnesses, the supervisor denied regularly passing wind in the communal office. He said he could not recall thrusting his backside at Mr Hingst and pretending to fart, although he conceded he could not rule it out either. "I may have done it once or twice, maybe. But I can't recall." One former employee said he witnessed Mr Short fart when he walked over to the printer but argued it was typical office "mucking around". He said Mr Hingst may have been offended because he was of German descent, "whereas us Australians are sort of brought up you sort of accept it or think oh it's just – that's what happens". Justice Zammit said the evidence suggested Mr Short's flatulence was "an offence that has its origins in cultural difference – rather than the sort of fear, distress, humiliation or victimisation that one would ordinarily expect in a bullying scenario". Flatulence not 'intimidation' The judge rejected claims about the frequency of the supervisor's flatulence or that it was targeted at Mr Hingst. She said even if the claims were true, it would not necessarily amount to bullying. "It is difficult to see how Mr Short's conduct could have intimidated or caused distress to the [administrator]," the judge said. "[Mr Hingst] was able to spray Mr Short with deodorant and give him the nickname 'Mr Stinky'. Indeed, on [his] own evidence, had he not lost his job and been abused over the telephone, the flatulence would 'never have been a big issue'." On allegations Mr Short yelled at Mr Hingst several times over the phone that he had "f---ed up" and was "not worth [his salary]", the judge found no supportive evidence for the claim. She concluded no Construction Engineering Australia staff had bullied or harassed Mr Hingst and noted evidence that domestic stress and dismissal probably led to Mr Hingst's psychiatric injuries. "It is in a sense tragic that the plaintiff's redundancy appears to lie at the heart of his problems. "It seems, regrettably, to have generated a misplaced sense of unfairness at the loss of his job."
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Carotenoid profiling, in silico analysis and transcript profiling of miRNAs targeting carotenoid biosynthetic pathway genes in different developmental tissues of tomato. Carotenoid biosynthetic pathway is one of the highly significant and very well elucidated secondary metabolic pathways in plants. microRNAs are the potential regulators, widely known for playing a pivotal role in the regulation of various biological as well as metabolic processes. miRNAs may assist in the metabolic engineering of the secondary metabolites for the production of elite genotypes with increased biomass and content of various metabolites. miRNA mediated regulation of carotenoid biosynthetic genes has not been elucidated so far. To illustrate the potential regulatory role of miRNAs in carotenoid biosynthesis, transcript profiling of the known miRNAs and their possible target carotenoid genes was undertaken at eight different developmental stages of tomato, using stem-loop PCR approach combined with quantitative RT-PCR. The inter-relationship amongst carotenoid content, biosynthetic genes and miRNAs was studied in depth. Comparative expression profiles of miRNA and target genes showed variable expression in different tissues studied. The expression level of miRNAs and their target carotenoid genes displayed similar pattern in the vegetative tissues as compared to the reproductive ones, viz. fruit (different stages), indicating the possibility of regulation of carotenoid biosynthesis at various stages of fruit development. This was later confirmed by the HPLC analysis of the carotenoids. The present study has further enhanced the understanding of regulation of carotenoid biosynthetic pathway in plants. The identified miRNAs can be employed to manipulate the biosynthesis of different carotenoids, through metabolic engineering for the production of lycopene rich tomatoes.
{ "pile_set_name": "PubMed Abstracts" }
Mortsel Mortsel () is a city and municipality close to the city of Antwerp located in the Belgian province of Antwerp. The municipality only comprises the city of Mortsel proper. On January 1, 2006 Mortsel had a total population of 24,427 people. The total area is 7.78 km² which gives a population density of 3,138 inhabitants per km². This is the highest population density of any municipality in the Flemish Region (Flanders), and second-highest (to Saint-Nicolas) outside the Brussels-Capital Region. Geography The city consists of the areas Mortsel-Dorp, Oude-God and Luithagen. Mortsel is bordered by Antwerp (districts Wilrijk, Berchem and Deurne), Borsbeek, Boechout, Hove, and Edegem. History Mortsel was the scene for one of the major collateral damage tragedies of World War II. On April 5, 1943, the Minerva car factory, then used to repair Luftwaffe planes, was the target of a big bombing raid by the USAAF. Unfortunately most bombs missed the target and hit a residential area instead, resulting in the deaths of 936 civilians, including 209 children, exceeding the civilian death toll of the Guernica raid which modern estimates put at 400. The last V2 launched against Antwerp also fell in Mortsel, killing 27 people, on March 27, 1945. Economy The headquarters of Agfa-Gevaert are situated in Mortsel. Notable people Alex Agnew, stand-up comedian Luc Brewaeys, (born in Mortsel in 1959), composer, conductor, pianist and recording producer Bart De Wever, politician Timo Descamps, actor Koen Lenaerts, President of the European Court of Justice Clem Schouwenaars (b. Mortsel, 1932–1993), writer Tamino, musician Luc Tuymans, painter Jos Vandeloo, writer See also the :Category:People from Mortsel. See also Crossing the Lines References External links Category:Municipalities of Antwerp (province) Category:Populated places in Antwerp (province) Category:Populated places in Belgium
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Eosinophil degranulation status in allergic rhinitis: observations before and during seasonal allergen exposure. Despite the fact that extensive degranulation is a likely prerequisite for a pathogenic role of eosinophils, little is known about the degranulation status of these cells in eosinophilic conditions. The present study of the ultrastructure of tissue eosinophils explores eosinophil degranulation in allergic rhinitis before and during seasonal allergen exposure. A total of 23 patients scored symptoms q.d., prior to and during the pollen season. The numbers of mucosal eosinophils and their degranulation status were determined in nasal biopsies. Furthermore, nasal lavage fluid levels of eosinophil cationic protein (ECP) and alpha2-macroglobulin were assessed as indices of eosinophil activity and plasma exudation, respectively. Seasonal allergen exposure was associated with increased nasal symptoms, increased lavage fluid levels of ECP and alpha2-macroglobulin, and increased numbers of tissue eosinophils. In the tissue, transmission electron microscopy revealed a moderate piecemeal degranulation already prior to the season (mean+/-sd 37+/-2.7% altered granules). Seasonal allergen exposure increased this degranulation (87+/-1.8%), and produced local areas with extensive deposition of granule proteins. The degree of eosinophil degranulation correlated with levels of ECP in lavage fluids obtained at histamine challenge. In conclusion, this study demonstrated that the nasal mucosa in allergic rhinitis features moderately degranulated eosinophils already at nonsymptomatic baseline conditions. In association with the development of symptomatic seasonal allergic rhinitis, the tissue deposition of eosinophil granule proteins is dramatically elevated through increased eosinophil numbers, together with markedly augmented degranulation of individual cells.
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Evaluation of four HIV antigen tests. A direct comparison of different HIV antigen assays is very helpful in making an informed choice, not only for the testing laboratories but also for healthcare workers in the developing world who are looking for reliable and inexpensive tests/methods in the follow-up of their treated patients. As a follow-up to the study published previously [Fransen K., Martens G., Stynen D., Goris A., Nys P., Nkengasong J., Heyndrickx L., Janssens W., van der Groen G., 1997. J. Med. Virol. 53, 31--35] where only two tests have been compared, four different commercial methods for HIV antigen determination in plasma and supernatant of cell cultures have now been evaluated on a limited sample size (88): COULTER HIV-1 p24 Antigen Assay (Coulter), (Test 1) INNOTEST HIV Antigen mAb (Innogenetics) (Test 2), Genetic Systems HIV-1 Ag EIA (Sanofi-Pasteur(1)) (Test 3) and VIDAS HIV P24 II (bioMérieux) (Test 4). Of the four tests used in this study, Test 2 was by far the most sensitive test. In a population of 88 follow-up samples from 35 different patients representing all stages of infection, the test detected confirmed p24 antigen at least once in 85.7% (30/35) of these patients, versus Test 3 in 74.3% (26/35), Test 4 in 71.4% (25/35), and Test 1 in 48.6% (17/35) of the patients. Test 2 detected confirmed p24 antigen in 84.9% of the follow-up samples, followed by Test 4 (65.9%), Test 3 (64.8%) and Test 1 (39.8%). Finally, Test 2 also proved best for detecting genetically diverse isolates.
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Conhecido como o "doleiro dos doleiros", Dario Messer disse a sua namorada, em uma conversa interceptada pela Polícia Federal, que pagou propina mensal ao procurador Januário Paludo, integrante da força-tarefa da "lava jato" no Ministério Público Federal do Paraná. A propina, segundo o doleiro, seria para evitar que ele fosse investigado. Reprodução/FacebookDoleiro disse que pagava propina mensal ao procurador Januário Paludo Os diálogos entre Messer e a namorada foram revelados neste sábado (30/11) pelo UOL. Segundo a reportagem, a conversa ocorreu em agosto de 2018 e foi obtida pela Polícia Federal do Rio de Janeiro. Em um relatório produzido em outubro, a PF classificou o fato como "grave" e cobrou providências. O documento já foi enviado à Procuradoria-Geral da República. Na conversa, Messer diz à namorada que uma testemunha de acusação de um dos processos contra ele teria uma reunião com Paludo. "Sendo que esse Paludo é destinatário de pelo menos parte da propina paga pelos meninos todo mês", afirmou o doleiro. Os meninos citados por Messer, segundo o UOL, seriam seus auxiliares em operações de lavagem de dinheiro e que, hoje, se tornaram delatores da "lava jato". Januário Paludo é um dos mais antigos integrantes da força-tarefa da "lava jato" e também um dos mais experientes. Atuou no caso Banestado nos anos 90. O nome dele apareceu algumas vezes na "vaza jato", série de reportagens com conversas privadas de procuradores que atuam na operação. Em uma delas, Paludo desdenhou do pedido do ex-presidente Lula para deixar a prisão e acompanhar o velório do irmão. "O safado só queria viajar", disse. Em nota, o MPF-PR repudiou "suposições infundadas contra o procurador". "A ação penal que tramitou contra Dario Messer em Curitiba foi de responsabilidade de outro procurador que atua na procuradoria da República no Paraná, o qual trabalhou no caso com completa independência. Nem o procurador Januário Paludo, nem a força-tarefa atuaram nesse processo", diz a nota. Ainda segundo o MPF, Messer é alvo de investigação na "lava jato" do Rio de Janeiro, "razão pela qual não faz sequer sentido a suposição de que um procurador da força-tarefa do Paraná poderia oferecer qualquer tipo de proteção". Por fim, os integrantes da força-tarefa afirmam ter plena confiança no trabalho de Paludo, "pessoa com extenso rol de serviços prestados à sociedade e respeitada no Ministério Público pela seriedade, profissionalismo e experiência".
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Queen Margaret University, Musselburgh A full ironmongery package for Queen Margaret University, Musselburgh. The new campus is a vibrant new academic village with high-tech buildings and attractive landscaped spaces, featuring an innovative learning resource centre at the heart of the development. The contractor was Grattan & Hynds. Recent Projects Traynor Williams Ironmongery strives to offer amazing customer service. We have a combined 100 years experience with a vast experience of architectural ironmongery. We have a wide range of clients throughout Scotland and the United Kingdom. What our clients say “We are happy with the consistently high standard of service and value the longstanding relationship we have with Traynor Williams Ironmongery. We happily recommend their services to any firm considering them for their ironmongery products and services.”
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GENOME ANNOUNCEMENT =================== The zygomycete *Rhizopus* microsporus is a terrestrial filamentous fungus that is used in food fermentation but also is known to cause rice seedling blight, which leads to substantial losses in agriculture, as well as mucormycoses in immunocompromised patients ([@B1], [@B2]). Phytopathogens, such as R. microsporus strain ATCC 62417, harbor endosymbiotic bacteria of the genus Burkholderia ([@B3], [@B4]) producing the antimitotic agent rhizoxin ([@B5][@B6][@B7]). Surprisingly, these symbiotic fungi lose their ability to produce mature sporangia and vegetative spores in the absence of the endobacteria ([@B8]). An analysis of the genome sequence of the endosymbiont Burkholderia rhizoxinica has revealed bacterial symbiosis factors ([@B9][@B10][@B12]). Besides information gained from genetic bar code studies ([@B13]), nothing is known about the genomic differences between symbiotic and symbiont-free R. microsporus strains. For each strain, multiple libraries (paired-end, 2-kb mate-pair, 3 × 5-kb mate-pair) were sequenced with Illumina HiSeq 2000. R. microsporus CBS 344.29 was additionally sequenced using Illumina MiSeq V2. The reads were quality trimmed, error corrected ([@B14]), digitally normalized ([@B15]), and finally assembled with AllPaths-LG ([@B16]) (LGC Genomics, Berlin, Germany). The assemblies were postprocessed using SOAP GapCloser ([@B17]). Transcriptome sequencing was performed using HiSeq 2000 100 bp. CBS 344.29 was cultured on potato dextrose agar (PDA) plates for 3 days at 30°C. ATCC 62417 was cultured under three different conditions, namely, with and without the endosymbiont (B. rhizoxinica) on PDA plates, and with bacterium in Vorkultur medium at 30°C for 3 days. The culture with Vorkultur medium was sequenced using the 454 FLX Titanium platform, and the contigs were assembled using Newbler (454 Life Sciences). rRNA was detected and removed with riboPicker ([@B18]). Structural and functional gene annotation were performed as described previously ([@B19], [@B20]). Protein sequences from *Lichtheimia hyalospora* (Joint Genome Institute \[JGI\]), *Mucor circinelloides* (Broad Institute), *Phycomyces blakesleeanus* (JGI), *Rhizopus delemar* (Broad Institute), and R. microsporus var. microsporus (JGI) were mapped to the reference genomes. The transcriptome assemblies of Newbler, Cufflinks ([@B21]), and genome-independent and genome-guided Trinity ([@B22]) were combined using EvidentialGene ([@B23]). The resulting assembly was checked for contamination with the help of BLAST, the NCBI nonredundant database, and the UniProt fungal knowledge base. The genome assembly is based on sequencing data amounting to 15.9 Gbp (CBS 344.29) and 15.7 Gbp (ATCC 62417), which represent a 310-fold estimated genome coverage. The assembly for CBS 344.29 consists of 1,554 scaffolds, with a total size of 49.2 Mbp (*N*~50~, 53 kbp), whereas the assembly of ATCC 62417 consists of 1,386 scaffolds, with a total size of 49.6 Mbp (*N*~50~, 198 kbp). The exceptionally low G+C content of the assemblies are 34.5% and 33.4%, respectively. Using CEGMA ([@B24]), we identified 431 and 451 core proteins within the respective genomes. During the genome annotation, we utilized RNA sequencing (RNA-seq) data amounting to 5.5 Mbp (CBS 344.29) and 5.1 Mbp (ATCC 62417), which represent an estimated 100-fold transcriptome coverage. For CBS 344.29, we predicted 19,564 genes and 20,209 transcripts, of which 10,698 have GO categories, 14,642 have InterPro domains, and 3,879 contain transmembrane domains. For ATCC 62417, we predicted 18,869 genes and 23,603 transcripts, of which 9,704 have GO categories, 17,264 have InterPro domains, and 4,807 contain transmembrane domains. The GO annotations of the fungus have been made available for enrichment analysis with FungiFun2 ([@B25]). Nucleotide sequence accession numbers. -------------------------------------- This whole-genome shotgun project has been deposited in DDBJ/ENA/GenBank under the accession numbers [CCYT01000001](CCYT01000001) to [CCYT01001386](CCYT01001386) (strain ATCC 62417) and [CDGI01000001](CDGI01000001) to [CDGI01001554](CDGI01001554) (strain CBS 344.29). The versions described in this paper are the first versions. The genome data and additional information are also available at the HKI Genome Resource (<http://www.genome-resource.de>/). **Citation** Horn F, Üzüm Z, Möbius N, Guthke R, Linde J, Hertweck C. 2015. Draft genome sequences of symbiotic and nonsymbiotic *Rhizopus microsporus* strains CBS 344.29 and ATCC 62417. Genome Announc. 3(1):e01370-14. doi:10.1128/genomeA.01370-14. This work was financially supported by the Deutsche Forschungsgemeinschaft (DFG), in the CRC/Transregio 124 "Pathogenic fungi and their human host: Networks of interaction," subproject INF (to J.L.) and in the Jena School for Microbial Communication (JSMC) (to Z.Ü. and N.M.).
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Q: OpenCart load Model outside Controller I'm working on an OpenCart project, that requires a lot of customization. for my project I have to change something in the cart library (system/library/cart.php). I would have to call a custom function that's defined inside the product model (catalog/model/catalog/product.php). In a controller, loading a Model and using its functions is easy: $this->load->model("catalog/product"); $this->model_catalog_product->customFunction(); But how do you load a model outside a controller? You can't create a new instance of the model, I already tried that: require_once("catalog/model/catalog/product.php"); $a_model = new ModelCatalogProduct(); This obviously doesn't work cause models weren't intended to be used in such a way. I also tried to use the scope resolution operator ( ModelCatalogProduct::customFunction()) It doesn't work either. I could pass all the required info as arguments, but I would rather use the model inside the cart library class, cause the changes would be global. Is it even possible to load a model outside a controller in OpenCart? A: If it's only one method that you need to copy, you would be best adding a method to the Cart class itself. The Cart class will work with the $this->db->query() calls as it already has $db assigned to it even though it's not a Controller/Model Edit Should you wish to do this, you could do something similar to the following public function test() { global $loader, $registry; $loader->model('catalog/product'); $model = $registry->get('model_catalog_product'); $result = $model->getProduct(123); } A: You are able to load a model outside a controlled. If You need to load a model inside of another model, You could load it the very same way using $this->load->model('my_module/my_model');. If You need to load a model inside of template file or other custom PHP script, look at the index.php file where the Registry is instanciated - You would need to instanciate it the same way. So Your custom code could look like: $registry = new Registry(); $my_model = $registry->load->model('my_module/my_model'); $my_model->customFunction(); Anyway I highly recommend not to edit/change the core library files unless You are sure there is no other way how to implement/do what You need. As Jay Gilford proposed I would implement that function or it's call to the catalog/checkout/cart.php, potentially confirm or success depending on the scope and functionality You would like to implement.
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[Desktop Entry] Name=Anbox GenericName=Android in a box Version=1.0 Type=Application Icon=anbox Exec=anbox launch --package=org.anbox.appmgr --component=org.anbox.appmgr.AppViewActivity Terminal=false
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Early voting turnout high Long lines form at the Coweta Voter Registration Office on the first day of early voting, and turnout has remained high. Cowetans, as well as voters all over the state, have been taking advantage of early voting in a big way. In the first three days of the 15-day early voting period, 4,047 Cowetans cast their ballots on the electronic voting machines. The Coweta Voter Registration Office had mailed out 2,155 absentee ballots. Be in the know the moment news happens Subscribe to Daily and Breaking News Alerts Email Address Election day is Nov. 6. Statewide, 211,861 early votes were cast by Oct. 16, according to Georgiavotes.com. That includes in-person early voting as well as absentee voting by mail. At the same time for the 2014 mid-term elections, the total was 67,372. This election bears more resemblance to the 2016 presidential election in terms of turnout than the 2014 midterms, according to Coweta Elections Superintendent Jane Scoggins. In 2014, a popular incumbent governor was on the ballot, while this year there is a fiercely contested and nationally watched governor’s race. Total early voting turnout in 2016 was 31,439, with 3,112 absentee ballots, according to Scoggins. Scoggins thinks Coweta might reach or beat that turnout this year. Typically, early voting starts off slow and turnout grows over time. “I expect it to stay busy. And we’re ready,” Scoggins said. Scoggins said she’s gotten quite a few phone calls from people who think something is wrong with their absentee ballot because there is no race for Coweta Sheriff on it. There are several candidates campaigning to succeed Sheriff Mike Yeager, but there is no election yet. Yeager has been nominated to be U.S. marshal for the Northern District of Georgia, but hasn’t yet been confirmed or taken that office, and is still Coweta’s sheriff. An election won’t be called until Yeager officially announces he is leaving the post. Scoggins is also seeing quite a few people turning in absentee ballots and having them canceled so they can vote on the electronic voting machines. If you’ve received an absentee ballot and decide you don’t want to vote by mail, simply bring your ballot to either the early voting location and have it canceled, or bring it to your polling place on election day. “You must bring that ballot with you,” Scoggins said. “Once you’ve been issued that ballot, it is like you’ve voted." Scoggins' office has received an unusually high number of absentee ballot requests. There are multiple organizations that have been sending people pre-printed ballot applications, Scoggins said. She’s had some people bring in the ballots and say they never requested them. When she shows them their signed ballot request, “They say ‘oh, I didn’t know that is what that was,’” she said. Early voting runs Monday through Friday, 8:30 a.m. to 4:30 p.m., through Nov. 2. There will be early voting Saturday, Oct. 27, from 9 a.m. to 4 p.m. Early voting takes place at two locations: the Coweta Voter Registration Office at 22 East Broad St. in downtown Newnan, and the Central Community Center, 65 Literary Lane, Newnan, near the intersection of Lower Fayetteville Road and Ga. Hwy. 154. For more information about early voting, call 770-254-2615 and press zero. Miss Your Newspaper? Please call 770-304-3373 to report a missed paper. If you did not receive your newspaper by 6:30 a.m. on Wednesday through Saturday or by 7 a.m. on Sunday, you can report it by calling our circulation number at 770-304-3373.You must call between 7 - 11 a.m. in order for a circulation representative to deliver a newspaper to you.
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Fast forward to 2030 and the children who started school in 2017 will need to be just as skilled in critical thinking, creativity and empathy as they are in literacy and numeracy and technology. It is impossible to accurately predict the jobs of the future, says Mark Scott, the secretary of the NSW Department of Education, but schools will need to prepare the next generations of students for a world that will be dominated by intelligent machines. "Children are now facing a more uncertain future than any child has faced since the Industrial Revolution," Mr Scott said. Mr Scott this week gave a speech to the Trans-Tasman Business Circle where he outlined publicly for the first time his vision for education of the future. It was the springboard for the launch of work being done within the department to prepare students for a fast-changing world.
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/* * Copyright (c) 1999 * Silicon Graphics Computer Systems, Inc. * * Copyright (c) 1999 * Boris Fomitchev * * This material is provided "as is", with absolutely no warranty expressed * or implied. Any use is at your own risk. * * Permission to use or copy this software for any purpose is hereby granted * without fee, provided the above notices are retained on all copies. * Permission to modify the code and to distribute modified code is granted, * provided the above notices are retained, and a notice that the code was * modified is included with the above copyright notice. * */ #ifndef _STLP_NUM_PUT_C #define _STLP_NUM_PUT_C #ifndef _STLP_INTERNAL_NUM_PUT_H # include <stl/_num_put.h> #endif #ifndef _STLP_INTERNAL_LIMITS # include <stl/_limits.h> #endif _STLP_BEGIN_NAMESPACE _STLP_MOVE_TO_PRIV_NAMESPACE // __do_put_float and its helper functions. Strategy: write the output // to a buffer of char, transform the buffer to _CharT, and then copy // it to the output. //---------------------------------------------------------------------- // num_put facet template <class _CharT, class _OutputIter> _OutputIter _STLP_CALL __copy_float_and_fill(const _CharT* __first, const _CharT* __last, _OutputIter __oi, ios_base::fmtflags __flags, streamsize __width, _CharT __fill, _CharT __xplus, _CharT __xminus) { if (__width <= __last - __first) return copy(__first, __last, __oi); else { streamsize __pad = __width - (__last - __first); ios_base::fmtflags __dir = __flags & ios_base::adjustfield; if (__dir == ios_base::left) { __oi = copy(__first, __last, __oi); return __fill_n(__oi, __pad, __fill); } else if (__dir == ios_base::internal && __first != __last && (*__first == __xplus || *__first == __xminus)) { *__oi++ = *__first++; __oi = __fill_n(__oi, __pad, __fill); return copy(__first, __last, __oi); } else { __oi = __fill_n(__oi, __pad, __fill); return copy(__first, __last, __oi); } } } #if !defined (_STLP_NO_WCHAR_T) // Helper routine for wchar_t template <class _OutputIter> _OutputIter _STLP_CALL __put_float(__iostring &__str, _OutputIter __oi, ios_base& __f, wchar_t __fill, wchar_t __decimal_point, wchar_t __sep, size_t __group_pos, const string& __grouping) { const ctype<wchar_t>& __ct = *__STATIC_CAST(const ctype<wchar_t>*, __f._M_ctype_facet()); __iowstring __wbuf; __convert_float_buffer(__str, __wbuf, __ct, __decimal_point); if (!__grouping.empty()) { __insert_grouping(__wbuf, __group_pos, __grouping, __sep, __ct.widen('+'), __ct.widen('-'), 0); } return __copy_float_and_fill(__CONST_CAST(wchar_t*, __wbuf.data()), __CONST_CAST(wchar_t*, __wbuf.data()) + __wbuf.size(), __oi, __f.flags(), __f.width(0), __fill, __ct.widen('+'), __ct.widen('-')); } #endif /* WCHAR_T */ // Helper routine for char template <class _OutputIter> _OutputIter _STLP_CALL __put_float(__iostring &__str, _OutputIter __oi, ios_base& __f, char __fill, char __decimal_point, char __sep, size_t __group_pos, const string& __grouping) { if ((__group_pos < __str.size()) && (__str[__group_pos] == '.')) { __str[__group_pos] = __decimal_point; } if (!__grouping.empty()) { __insert_grouping(__str, __group_pos, __grouping, __sep, '+', '-', 0); } return __copy_float_and_fill(__CONST_CAST(char*, __str.data()), __CONST_CAST(char*, __str.data()) + __str.size(), __oi, __f.flags(), __f.width(0), __fill, '+', '-'); } template <class _CharT, class _OutputIter, class _Float> _OutputIter _STLP_CALL __do_put_float(_OutputIter __s, ios_base& __f, _CharT __fill, _Float __x) { __iostring __buf; size_t __group_pos = __write_float(__buf, __f.flags(), (int)__f.precision(), __x); const numpunct<_CharT>& __np = *__STATIC_CAST(const numpunct<_CharT>*, __f._M_numpunct_facet()); return __put_float(__buf, __s, __f, __fill, __np.decimal_point(), __np.thousands_sep(), __group_pos, __f._M_grouping()); } inline void __get_money_digits_aux (__iostring &__buf, ios_base &, _STLP_LONGEST_FLOAT_TYPE __x) { __get_floor_digits(__buf, __x); } #if !defined (_STLP_NO_WCHAR_T) inline void __get_money_digits_aux (__iowstring &__wbuf, ios_base &__f, _STLP_LONGEST_FLOAT_TYPE __x) { __iostring __buf; __get_floor_digits(__buf, __x); const ctype<wchar_t>& __ct = *__STATIC_CAST(const ctype<wchar_t>*, __f._M_ctype_facet()); __convert_float_buffer(__buf, __wbuf, __ct, wchar_t(0), false); } #endif template <class _CharT> void _STLP_CALL __get_money_digits(_STLP_BASIC_IOSTRING(_CharT) &__buf, ios_base& __f, _STLP_LONGEST_FLOAT_TYPE __x) { __get_money_digits_aux(__buf, __f, __x); } // _M_do_put_integer and its helper functions. template <class _CharT, class _OutputIter> _OutputIter _STLP_CALL __copy_integer_and_fill(const _CharT* __buf, ptrdiff_t __len, _OutputIter __oi, ios_base::fmtflags __flg, streamsize __wid, _CharT __fill, _CharT __xplus, _CharT __xminus) { if (__len >= __wid) return copy(__buf, __buf + __len, __oi); else { //casting numeric_limits<ptrdiff_t>::max to streamsize only works is ptrdiff_t is signed or streamsize representation //is larger than ptrdiff_t one. _STLP_STATIC_ASSERT((sizeof(streamsize) > sizeof(ptrdiff_t)) || (sizeof(streamsize) == sizeof(ptrdiff_t)) && numeric_limits<ptrdiff_t>::is_signed) ptrdiff_t __pad = __STATIC_CAST(ptrdiff_t, (min) (__STATIC_CAST(streamsize, (numeric_limits<ptrdiff_t>::max)()), __STATIC_CAST(streamsize, __wid - __len))); ios_base::fmtflags __dir = __flg & ios_base::adjustfield; if (__dir == ios_base::left) { __oi = copy(__buf, __buf + __len, __oi); return __fill_n(__oi, __pad, __fill); } else if (__dir == ios_base::internal && __len != 0 && (__buf[0] == __xplus || __buf[0] == __xminus)) { *__oi++ = __buf[0]; __oi = __fill_n(__oi, __pad, __fill); return copy(__buf + 1, __buf + __len, __oi); } else if (__dir == ios_base::internal && __len >= 2 && (__flg & ios_base::showbase) && (__flg & ios_base::basefield) == ios_base::hex) { *__oi++ = __buf[0]; *__oi++ = __buf[1]; __oi = __fill_n(__oi, __pad, __fill); return copy(__buf + 2, __buf + __len, __oi); } else { __oi = __fill_n(__oi, __pad, __fill); return copy(__buf, __buf + __len, __oi); } } } #if !defined (_STLP_NO_WCHAR_T) // Helper function for wchar_t template <class _OutputIter> _OutputIter _STLP_CALL __put_integer(char* __buf, char* __iend, _OutputIter __s, ios_base& __f, ios_base::fmtflags __flags, wchar_t __fill) { locale __loc = __f.getloc(); // const ctype<wchar_t>& __ct = use_facet<ctype<wchar_t> >(__loc); const ctype<wchar_t>& __ct = *__STATIC_CAST(const ctype<wchar_t>*, __f._M_ctype_facet()); wchar_t __xplus = __ct.widen('+'); wchar_t __xminus = __ct.widen('-'); wchar_t __wbuf[64]; __ct.widen(__buf, __iend, __wbuf); ptrdiff_t __len = __iend - __buf; wchar_t* __eend = __wbuf + __len; // const numpunct<wchar_t>& __np = use_facet<numpunct<wchar_t> >(__loc); // const string& __grouping = __np.grouping(); const numpunct<wchar_t>& __np = *__STATIC_CAST(const numpunct<wchar_t>*, __f._M_numpunct_facet()); const string& __grouping = __f._M_grouping(); if (!__grouping.empty()) { int __basechars; if (__flags & ios_base::showbase) switch (__flags & ios_base::basefield) { case ios_base::hex: __basechars = 2; break; case ios_base::oct: __basechars = 1; break; default: __basechars = 0; } else __basechars = 0; __len = __insert_grouping(__wbuf, __eend, __grouping, __np.thousands_sep(), __xplus, __xminus, __basechars); } return __copy_integer_and_fill((wchar_t*)__wbuf, __len, __s, __flags, __f.width(0), __fill, __xplus, __xminus); } #endif // Helper function for char template <class _OutputIter> _OutputIter _STLP_CALL __put_integer(char* __buf, char* __iend, _OutputIter __s, ios_base& __f, ios_base::fmtflags __flags, char __fill) { char __grpbuf[64]; ptrdiff_t __len = __iend - __buf; // const numpunct<char>& __np = use_facet<numpunct<char> >(__f.getloc()); // const string& __grouping = __np.grouping(); const numpunct<char>& __np = *__STATIC_CAST(const numpunct<char>*, __f._M_numpunct_facet()); const string& __grouping = __f._M_grouping(); if (!__grouping.empty()) { int __basechars; if (__flags & ios_base::showbase) switch (__flags & ios_base::basefield) { case ios_base::hex: __basechars = 2; break; case ios_base::oct: __basechars = 1; break; default: __basechars = 0; } else __basechars = 0; // make sure there is room at the end of the buffer // we pass to __insert_grouping copy(__buf, __iend, (char *) __grpbuf); __buf = __grpbuf; __iend = __grpbuf + __len; __len = __insert_grouping(__buf, __iend, __grouping, __np.thousands_sep(), '+', '-', __basechars); } return __copy_integer_and_fill(__buf, __len, __s, __flags, __f.width(0), __fill, '+', '-'); } #if defined (_STLP_LONG_LONG) typedef _STLP_LONG_LONG __max_int_t; typedef unsigned _STLP_LONG_LONG __umax_int_t; #else typedef long __max_int_t; typedef unsigned long __umax_int_t; #endif _STLP_DECLSPEC const char* _STLP_CALL __hex_char_table_lo(); _STLP_DECLSPEC const char* _STLP_CALL __hex_char_table_hi(); template <class _Integer> inline char* _STLP_CALL __write_decimal_backward(char* __ptr, _Integer __x, ios_base::fmtflags __flags, const __true_type& /* is_signed */) { const bool __negative = __x < 0 ; __max_int_t __temp = __x; __umax_int_t __utemp = __negative?-__temp:__temp; for (; __utemp != 0; __utemp /= 10) *--__ptr = (char)((int)(__utemp % 10) + '0'); // put sign if needed or requested if (__negative) *--__ptr = '-'; else if (__flags & ios_base::showpos) *--__ptr = '+'; return __ptr; } template <class _Integer> inline char* _STLP_CALL __write_decimal_backward(char* __ptr, _Integer __x, ios_base::fmtflags __flags, const __false_type& /* is_signed */) { for (; __x != 0; __x /= 10) *--__ptr = (char)((int)(__x % 10) + '0'); // put sign if requested if (__flags & ios_base::showpos) *--__ptr = '+'; return __ptr; } template <class _Integer> char* _STLP_CALL __write_integer_backward(char* __buf, ios_base::fmtflags __flags, _Integer __x) { char* __ptr = __buf; if (__x == 0) { *--__ptr = '0'; if ((__flags & ios_base::showpos) && ((__flags & (ios_base::oct | ios_base::hex)) == 0)) *--__ptr = '+'; // oct or hex base shall not be added to the 0 value (see '#' flag in C formating strings) } else { switch (__flags & ios_base::basefield) { case ios_base::oct: { __umax_int_t __temp = __x; // if the size of integer is less than 8, clear upper part if ( sizeof(__x) < 8 && sizeof(__umax_int_t) >= 8 ) __temp &= 0xFFFFFFFF; for (; __temp != 0; __temp >>=3) *--__ptr = (char)((((unsigned)__temp)& 0x7) + '0'); // put leading '0' if showbase is set if (__flags & ios_base::showbase) *--__ptr = '0'; } break; case ios_base::hex: { const char* __table_ptr = (__flags & ios_base::uppercase) ? __hex_char_table_hi() : __hex_char_table_lo(); __umax_int_t __temp = __x; // if the size of integer is less than 8, clear upper part if ( sizeof(__x) < 8 && sizeof(__umax_int_t) >= 8 ) __temp &= 0xFFFFFFFF; for (; __temp != 0; __temp >>=4) *--__ptr = __table_ptr[((unsigned)__temp & 0xF)]; if (__flags & ios_base::showbase) { *--__ptr = __table_ptr[16]; *--__ptr = '0'; } } break; //case ios_base::dec: default: { #if defined(__HP_aCC) && (__HP_aCC == 1) bool _IsSigned = !((_Integer)-1 > 0); if (_IsSigned) __ptr = __write_decimal_backward(__ptr, __x, __flags, __true_type() ); else __ptr = __write_decimal_backward(__ptr, __x, __flags, __false_type() ); #else typedef typename __bool2type<numeric_limits<_Integer>::is_signed>::_Ret _IsSigned; __ptr = __write_decimal_backward(__ptr, __x, __flags, _IsSigned()); #endif } break; } } // return pointer to beginning of the string return __ptr; } template <class _CharT, class _OutputIter, class _Integer> _OutputIter _STLP_CALL __do_put_integer(_OutputIter __s, ios_base& __f, _CharT __fill, _Integer __x) { // buffer size = number of bytes * number of digit necessary in the smallest Standard base (base 8, 3 digits/byte) // plus the longest base representation '0x' // Do not use __buf_size to define __buf static buffer, some compilers (HP aCC) do not accept const variable as // the specification of a static buffer size. char __buf[sizeof(_Integer) * 3 + 2]; const ptrdiff_t __buf_size = sizeof(__buf) / sizeof(char); ios_base::fmtflags __flags = __f.flags(); char* __ibeg = __write_integer_backward((char*)__buf+__buf_size, __flags, __x); return __put_integer(__ibeg, (char*)__buf+__buf_size, __s, __f, __flags, __fill); } _STLP_MOVE_TO_STD_NAMESPACE // // num_put<> // #if (_STLP_STATIC_TEMPLATE_DATA > 0) # if !defined (__BORLANDC__) template <class _CharT, class _OutputIterator> locale::id num_put<_CharT, _OutputIterator>::id; # endif # if (defined (__CYGWIN__) || defined (__MINGW32__)) && \ defined (_STLP_USE_DYNAMIC_LIB) && !defined (__BUILDING_STLPORT) /* * Under cygwin, when STLport is used as a shared library, the id needs * to be specified as imported otherwise they will be duplicated in the * calling executable. */ template <> _STLP_DECLSPEC locale::id num_put<char, ostreambuf_iterator<char, char_traits<char> > >::id; /* template <> _STLP_DECLSPEC locale::id num_put<char, char*>::id; */ # if !defined (_STLP_NO_WCHAR_T) template <> _STLP_DECLSPEC locale::id num_put<wchar_t, ostreambuf_iterator<wchar_t, char_traits<wchar_t> > >::id; /* template <> _STLP_DECLSPEC locale::id num_put<wchar_t, wchar_t*>::id; */ # endif # endif /* __CYGWIN__ && _STLP_USE_DYNAMIC_LIB */ #else /* ( _STLP_STATIC_TEMPLATE_DATA > 0 ) */ //typedef num_put<char, char*> num_put_char; typedef num_put<char, ostreambuf_iterator<char, char_traits<char> > > num_put_char_2; //__DECLARE_INSTANCE(locale::id, num_put_char::id, ); __DECLARE_INSTANCE(locale::id, num_put_char_2::id, ); # if !defined (_STLP_NO_WCHAR_T) //typedef num_put<wchar_t, wchar_t*> num_put_wchar_t; typedef num_put<wchar_t, ostreambuf_iterator<wchar_t, char_traits<wchar_t> > > num_put_wchar_t_2; //__DECLARE_INSTANCE(locale::id, num_put_wchar_t::id, ); __DECLARE_INSTANCE(locale::id, num_put_wchar_t_2::id, ); # endif #endif /* ( _STLP_STATIC_TEMPLATE_DATA > 0 ) */ // issue 118 #if !defined (_STLP_NO_BOOL) template <class _CharT, class _OutputIter> _OutputIter num_put<_CharT, _OutputIter>::do_put(_OutputIter __s, ios_base& __f, char_type __fill, bool __val) const { if (!(__f.flags() & ios_base::boolalpha)) return this->do_put(__s, __f, __fill, __STATIC_CAST(long,__val)); locale __loc = __f.getloc(); // typedef numpunct<_CharT> _Punct; // const _Punct& __np = use_facet<_Punct>(__loc); const numpunct<_CharT>& __np = *__STATIC_CAST(const numpunct<_CharT>*, __f._M_numpunct_facet()); basic_string<_CharT> __str = __val ? __np.truename() : __np.falsename(); // Reuse __copy_integer_and_fill. Since internal padding makes no // sense for bool, though, make sure we use something else instead. // The last two argument to __copy_integer_and_fill are dummies. ios_base::fmtflags __flags = __f.flags(); if ((__flags & ios_base::adjustfield) == ios_base::internal) __flags = (__flags & ~ios_base::adjustfield) | ios_base::right; return _STLP_PRIV __copy_integer_and_fill(__str.c_str(), __str.size(), __s, __flags, __f.width(0), __fill, (_CharT) 0, (_CharT) 0); } #endif template <class _CharT, class _OutputIter> _OutputIter num_put<_CharT, _OutputIter>::do_put(_OutputIter __s, ios_base& __f, _CharT __fill, long __val) const { return _STLP_PRIV __do_put_integer(__s, __f, __fill, __val); } template <class _CharT, class _OutputIter> _OutputIter num_put<_CharT, _OutputIter>::do_put(_OutputIter __s, ios_base& __f, _CharT __fill, unsigned long __val) const { return _STLP_PRIV __do_put_integer(__s, __f, __fill, __val); } template <class _CharT, class _OutputIter> _OutputIter num_put<_CharT, _OutputIter>::do_put(_OutputIter __s, ios_base& __f, _CharT __fill, double __val) const { return _STLP_PRIV __do_put_float(__s, __f, __fill, __val); } #if !defined (_STLP_NO_LONG_DOUBLE) template <class _CharT, class _OutputIter> _OutputIter num_put<_CharT, _OutputIter>::do_put(_OutputIter __s, ios_base& __f, _CharT __fill, long double __val) const { return _STLP_PRIV __do_put_float(__s, __f, __fill, __val); } #endif #if defined (_STLP_LONG_LONG) template <class _CharT, class _OutputIter> _OutputIter num_put<_CharT, _OutputIter>::do_put(_OutputIter __s, ios_base& __f, _CharT __fill, _STLP_LONG_LONG __val) const { return _STLP_PRIV __do_put_integer(__s, __f, __fill, __val); } template <class _CharT, class _OutputIter> _OutputIter num_put<_CharT, _OutputIter>::do_put(_OutputIter __s, ios_base& __f, _CharT __fill, unsigned _STLP_LONG_LONG __val) const { return _STLP_PRIV __do_put_integer(__s, __f, __fill, __val); } #endif /* _STLP_LONG_LONG */ // lib.facet.num.put.virtuals "12 For conversion from void* the specifier is %p." template <class _CharT, class _OutputIter> _OutputIter num_put<_CharT, _OutputIter>::do_put(_OutputIter __s, ios_base& __f, _CharT /*__fill*/, const void* __val) const { const ctype<_CharT>& __c_type = *__STATIC_CAST(const ctype<_CharT>*, __f._M_ctype_facet()); ios_base::fmtflags __save_flags = __f.flags(); __f.setf(ios_base::hex, ios_base::basefield); __f.setf(ios_base::showbase); __f.setf(ios_base::internal, ios_base::adjustfield); __f.width((sizeof(void*) * 2) + 2); // digits in pointer type plus '0x' prefix # if defined(_STLP_LONG_LONG) && !defined(__MRC__) //*ty 11/24/2001 - MrCpp can not cast from void* to long long _OutputIter result = this->do_put(__s, __f, __c_type.widen('0'), __REINTERPRET_CAST(unsigned _STLP_LONG_LONG,__val)); # else _OutputIter result = this->do_put(__s, __f, __c_type.widen('0'), __REINTERPRET_CAST(unsigned long,__val)); # endif __f.flags(__save_flags); return result; } _STLP_END_NAMESPACE #endif /* _STLP_NUM_PUT_C */ // Local Variables: // mode:C++ // End:
{ "pile_set_name": "Github" }
List of ambassadors of China to Belgium The Chinese ambassador to Belgium is the official representative of the government of China to the government of Belgium. From 1973 to 2005 the Chinese ambassador in Brussels was also accredited to the European Community. List of Representatives References Ministry of Foreign Affairs of the People's Republic of China'', Chinese Ambassadors to Belgium, 驻比利时王国历任大使 </ref> Belgium China
{ "pile_set_name": "Wikipedia (en)" }
Q: Storing a String array in the SharedPreferences I was wondering if it could be possible to save in the shared preferences an array of Strings, in a way that, every time we save a certain String, we store it in that array. For example I have a list of locations with a certain ID that I want to mark as favorite. The ideal situation would be, having an array and saving a certain location ID (let's call it Location1) in that array, so next time I want to mark a new location as favorite (let's call it Location2), I retrieve that array (which so far contains Location1) and add the ID of this new location I want to add (Location2). Android has methods to store primitive objects, but not for arrays. Any idea in order to do this, please? A: This is doable: I was just blogging about it: SAVE YOUR ARRAY //String array[] //SharedPreferences prefs Editor edit = prefs.edit(); edit.putInt("array_size", array.length); for(int i=0;i<array.length; i++) edit.putString("array_" + i, array[i]); edit.commit(); RETRIEVE YOUR ARRAY int size = prefs.getInt("array_size", 0); array = new String[size]; for(int i=0; i<size; i++) prefs.getString("array_" + i, null); Just wrote that so there might be typos. A: You could make the array a JSON array and then store it like this: SharedPreferences settings = getSharedPreferences("SETTINGS KEY", 0); SharedPreferences.Editor editor = settings.edit(); JSONArray jArray = new JSONArray(); try { jArray.put(id); } catch (JSONException e) { e.printStackTrace(); } editor.putString("jArray", jArray.toString()); editor.commit(); You can then get the array like this: SharedPreferences settings = getSharedPreferences("SETTINGS KEY", 0); try { JSONArray jArray = new JSONArray(settings.getString("jArray", "")); } catch (JSONException e) { e.printStackTrace(); } Just an alternative solution that I have used in the past A: Write methods to read and write a serialized array. This shouldn't be too difficult. Just flatten the array of strings into a single string that you store in the preferences. Another option would be to convert the array into an XML structure that you then store in the preferences, but that is probably overkill.
{ "pile_set_name": "StackExchange" }
Igor Muradyan Igor Muradyan (; 29 April 1957 – 17 June 2018) was an Armenian political activist and politologist. He was one of the earliest leaders of the Karabakh movement, along with Zori Balayan, Silva Kaputikyan and Viktor Hambardzumyan. Born in Odessa, Muradyan grew up in Baku, where many Armenians lived during the Soviet period. He finished the Plekhanov Institute of National Economy in Moscow. According to Thomas de Waal, "Muradian was a Soviet insider. He worked as an economist in the state planning agency Gosplan in Yerevan and had good connections among Party cadres." Muradyan was later critical of the Nagorno-Karabakh authorities, calling the unrecognised Nagorno-Karabakh Republic "a failed experiment" and criticising its authorities for not being able to come up with a clear strategy for its existence and arguing for Nagorno-Karabakh's incorporation into Armenia. References External links Category:Armenian activists Category:People from the Republic of Artsakh Category:1957 births Category:Azerbaijani Armenians Category:2018 deaths Category:Armenian political scientists Category:Members of the Karabakh Committee
{ "pile_set_name": "Wikipedia (en)" }
Move max distance you can and measure how long they actually moved, then recalculate the steps.IE if you have 100 steps/mm and you set it to move 10mm and it only moved 8 then you need more steps/mm(100/8)*10 = new steps/mm Np, You can find my facebook group here, if you like. It's a bit easier talking there :) https://www.facebook.com/betrue3d/Cheers I cant remember how I came to it, but I think I read somehwere that a huge amount of steps was needed, so I entered a very high number, but you calculate it the same way. It's the drive from a floppy drive, hence the difference.Ie start with 6000 or something and see :) The Micro SD is not meant to store .gcode files on an print, unless you upload files to it through terminal or lan, which are rather flaky on this.You use SD card reader in TFT or similar or print via USB. Heya LarryThanks.1) Yes, if they have same voltage.2) You copy the setup for the fan you use but just specify the new pin. If you only have one extruder as most people, the extruder 2 pin is free P2.63) http://smoothieware.org/3d-printer-guide#using-two-steppers-motor-on-a-single-driverHope it helps :) If you want access to your network from some other network, you always need to setup your router to portforward the necesary ports as well as setup firewall in your router (not all routers announce them as seperate functions).Everything can be viewed remotely this way. Always. Just a matter of configuring the network.MAC: you might need mac versions of the programs, but don't see why not.Just keep in mind that this instructables contains ALL steps, and you might not need all steps for your particular setup.Maybe take a look at Astroprint. I like that way more than OctoPrint :) The things you mention are not electronic words or anything.. have you tried googling the words?Protrusion = Something that protudes from something.Washers = round flat metal discs with hole in the middle for your screw.Mount holes = the holes you use to mount/attach the partsYou really just need to make prepare the moving part so you can attach things to it. Flatten/cut away as necessary, and drill holes you might need.Try look in here, as they made a nice manual. You can use their info even though you don't print the parts as they do.https://www.thingiverse.com/thing:902826 When you say internet, do you mean your local wireless network?You don't have to have it on internet. I don't know how you woud controll it without having it on your local network.You can't use USB or SD in your printer? That would be the best option if you don't use the remote options in Octoprint in any case. Have you tried using Google?https://www.google.dk/search?q=3d+printer+solid+state+relay&oq=3D+printer+solid+stateBut here's a thread:http://www.soliforum.com/topic/9004/sd4-heatbed-installation/I'm a bit confused as you say the hotbed output gives 110VAC... the hotebed does not provide any output. You can say how much Wattage it is rated at and what voltage it needs. This will give you the amperage your PSU at least needs to be + 20%Why do you need 5v to activate it the bed/SSR? It's easier just to use the bed output.Hope it helps.Cheers For the heater problem you propably need to define your heater 2 with the correct pins - meaning other pins than you use for heater 1.After you have defined the pins correctly, you should do the mandatory PID tuning of the heater :) I'm actually not sure, but I have been asked this before.I personally used an external driver board and driver connected to the pins on the driver I wanted to "clone". This way they are given the exact same instructions. Without jumpers means you run without microstepping.If you insert all 3 jumpers it might not move at all at untill you modify steps/mm since it means 1/16 microstepping. If you use the jumpers and modify the steps you are going to get a much smoother and quieter result. The torque is also going to be a tad less, but nothing you should be able to notice on a 3D printer.What is your steps/mm now? Hello entropy,You just solder all pins on. Regardless of jumpersettings.Jumpers depends on multistepping settings you want to achieve. I've corrected the jumper table. It had lost it formating for some reason.I recommend having all 3 jumpers in place to use highest microstepping.CNC people are going to say you should run wiht lowest multistepping as possible for greatest power, but 3D printer is not a CNC, and we want the smoother running -> lower noice while the power is still plenty for any 3D Printer.jumper Yes/No step size1 2 3no no no full stepyes no no half stepno yes no 1/4 stepyes yes no 1/8 stepyes yes yes 1/16 step Here are a couple of explanatatory pages:https://www.circuitspecialists.com/blog/unipolar-stepper-motor-vs-bipolar-stepper-motors/andhttps://www.quora.com/What-is-the-difference-between-bipolar-unipolar-stepper-motorBut really, you just want bipolar motors.I don't know what "idk" means. We are from many different countries, so using abbreviations often ruins the understanding between us. Same with "plz", which _I_ know means please, but again... abbreviations are bad, especially made up ones :) I don't know what you mean with "chopping constant durrent drive"?Id say that you should find a different motor, if it doesn't work using an a4988 driver :) Nice find! I havn't had this issue myself, so quite odd. Your firmware is much newer than when I used Marlin though, so it might have changed.If you have the energy to do so, you should report it on the Github site for Marlin. Have you tried with different Gcode files? Made sure the baudrate is the same on display and in firmware? (It must be since you can move it, but just to be sure).Try updating firmware on both.The MKS Base 1.5 is not smoothieware but normal 8bit marlinhttps://www.aliexpress.com/store/product/3D-Printer-Control-motherboard-MKS-BASE-V1-0-compatible-RAMPS-1-4-Printer-Control-Reprap-MendelPrusa/1047297_2031109769.htmlNewest 32bit Smoothiewaere is MKS Sbase 1,3 https://www.aliexpress.com/store/product/3Dpriter-control-board-MKS-SBase-V1-0-32-s-Motherboard-compatible-Smoothieware-open-source-firmware-support/1047297_32384368763.htmlNotice how smoothieware is Sbase, and the other is BaseRegards,MortenDenmark Hello CharleWThank you for your feedback. In order to use the LCD12864 you need to scroll down in the configuration.h file and uncomment the:REPRAP_DISCOUNT_FULL_GRAPHIC_SMART_CONTROLLERIt is not:REPRAP_DISCOUNT_SMART_CONTROLLERYou can get more info on your LCD here:http://reprap.org/wiki/RepRapDiscount_Full_Graphic_Smart_ControllerHope it helps Heya mshievitz. It's stable now? Asking as I played a bit with it (not overly much), but had some issues with the fans I use to cool the printed objects.Can't rule out wheter it was just the fans though :)Nice input :) Hello HIM,I do not own an MKS Gen 1,4 board.You are welcome to contact MKS and ask for it, as they might want me to make an instructables, if enough people are asking for it.The Gen 1,4 is working as Ramps 1.4 but with a bit different layout. It's much cheaper to buy directly from the manufacturer. Even though you have to pay import taxes and vat etc.But we have a few sellers in Denmark. I don't know about their shipping policy or pricing though.http://3deksperten.dk/mks-sbase-v1-3-controller-board-mainboard-32bit.htmlRegards,Morten I have no experience using smoothieware on corexy, but I guess it should work fine.I do not know if second homing works differently on CoreXY. Is it important for you it moves out and back in?Firmware from makerbase.com is just a really old version of the original firmware, so I'll not recommend using that.I'll recommend you go back to new firmware and check your endstops are working.Reason for the "noise from steppers untill reset" is because they are powered on. You can issue the Gcode M18 http://reprap.org/wiki/G-code#M18:_Disable_all_stepper_motors to turn motors off. This will remove the noise and make steppers easy to move.You should not move the steppers/axes manually with motors engaged. Worst case you can ruin the drivers on the controller board. Win_install.cmd is only if you want to compile your own firmware - we don't want to do that. At least not in my instructables, where we use the pre-compiled firmware.bin filesNot entirely sure what you mean about config file, but I think you have misunderstodd how the firmware works.1) You do not want/need to use the win_install.cmd to compile your own firmware.2) You copy over the firmware.bin file from smoothiewares github (I link directly to it)3) You copy over your config.txt file4) You power off - including remove USB.5) Reconnect USB and the card flashes (reads) the firmware to the card.6) The firmware.bin file is automatically renamed firmware.curRegarding 12v. Might be because your 5v through USB isn't high enough amperage. Edited the section regarding drivers and firmware in an attempt to make it more clear to use MKS drivers and firmware from Smoothieware.I removed some links directed at MKS, as they removed the info I linked to. They have changed some on their Github, but I'm trying to find out why and what. (asking them)Remember the "nice comment policy" people. In the past days we have had an unfortunate individual trolling in here, which is rather sad all considering. I'm not attacking Smoothieware. I'm PROMOTING smoothieware. FOR FREE.What I am doing is helping people for free. Doing your work. For Free. I'm stating facts about the unfriendly tone of your Google groups, as thousands of people see them (gathered from all the countless messages I recieve).It's ok you view it differently, since you have promoted that kind of environment.Just please do not come over here, and ruin the good mood.In this forum, we try to HELP each other. Not Critize each other. Regarding your "document".. I can put together an endless list of pointless attacks you have made, here, on your own foras, github and especially on the reprap forums.. but I try to focus on furthering the community, not hammering anyone.Yes, I can get carried away now and then, I am humand, and this is not my work, so my work cap is not on... but I do not go search for people to annoy.. like you do here.Can't you see how bad it is you come here like this Arthur? I'm freaking trying to promote Smoothieware, but you, as the people who has most to gain, work very actively to destroy it by being so darned negative. You know you can save as draft and then publish it all when you are done?Reprap.me, the maker of the Original Diamond Hotend, are working on a 5way Diamond Hotend now. Just to answer @Tengo10Heatsinks not being properly prepared on this photo, but the Diamond tip is :) I have crimped my own motor wires. I usually start using a needle-clamp (I think it's called that. I'm danish). I then use a very cheap crimp tool I bought in Biltema (Scandinavian store). But it's the same as any cheap crimp tool you can buy anywhere. Sometimes tweak it with my needle-plier after crimping to make it fit into the plugs. Hello Googliola. I believe you can run must of the gpio pins as pwn though not as true "hpwm" setting? Just a thought?I really do not know about the on off stuff. I always turn my printer physically on/off, and it sounds like you are more at home with the configuration than me ?I'm sure you can ask on smoothies google groups on how to use it. They might have an idea. Just don't start out with "hi, I'm using MKS Sbase board..." ? problem is that for most people it is much easier to setup using a graphical interface.If all else fails, go check out Astroprint. I vastly prefer that one over Octoprint as well, since it was made for normal people, and with focus on intuitive usage and not geekstuff over useability like Octoprint. Hello Kanataa.You are correct, I do have an Ultimaker where it homes to the bottom, meaning to MAX.The way to fault find is:1) Connect using Pronterface 2) Check endstop status by issuing M119. Correct firmware if necessary.3) Check your Z moves the desired direction when you hit the move buttons. + = bed moves away from nozzle.4) Adjust firmware if needed to correct direction of move.5) Be ready to turn off power and then hit Z-home - G28 Z06) If it moves the wrong way, check that Z-min is 0 and Z max is 200 (or what your max is)7) try again.I have written 2 Instructables about <a href="https://www.instructables.com/id/Motion-Configurati... target="_blank">Motion Configuration</a> and <a href="https://www.instructables.com/id/Configuring-Endsto... tar... Hello Kanataa.You are correct, I do have an Ultimaker where it homes to the bottom, meaning to MAX.The way to fault find is:1) Connect using Pronterface 2) Check endstop status by issuing M119. Correct firmware if necessary.3) Check your Z moves the desired direction when you hit the move buttons. + = bed moves away from nozzle.4) Adjust firmware if needed to correct direction of move.5) Be ready to turn off power and then hit Z-home - G28 Z06) If it moves the wrong way, check that Z-min is 0 and Z max is 200 (or what your max is)7) try again.I have written 2 Instructables about <a href="https://www.instructables.com/id/Motion-Configurati... target="_blank">Motion Configuration</a> and <a href="https://www.instructables.com/id/Configuring-Endsto... target="_blank">Configuring endstops</a> which you might find helpful.You can ofcourse also write here :) Thank you for your nice words.I'm sorry I really don't have any ideas other than Googling, and I think it's better you do your own googling :)If you have the option to hook up the pi to a monitor and keyboard it will make it easier for you?Cheers,Morten I'd try to contact the seller. I am not MKS or even an affiliate. I just write Instructables for topics I find interesting :) Ok. That might be nice for some people :)I havn't seen any officially supported firmwares on the smoothieboard platform. I'm just personally loath to get firmware with only partial support.I used Marlin for a long time and never was a fan. Just too messy, and the whole compile procedure alone was enough for me to dump it :)I make lots of changes all the time though, which most people don't do.I'm going to jump on the Duet Wifi soon. Just waiting to recieve the Duex5 expansion board to go with Diamond hotend 5way prototype <wink> Awesome info HaydnH.It can't be fixed by setting segment size to very small in firmware? (I havn't read up on it) Awesome. Glad you found the problem. I've been rather busy with my new Extruder http://www.thingiverse.com/thing:1914288 , so havn't had time to look it up myself.I must admit I'm totally at a loss when people say "pull-up" but I know you can shift a jumper to decide wheter the voltage on endstops are 3.3 or 5v If it is S3D I think you should contact them. It is a paid commercial product so they might be able to help some.I would test using Cura or other slizer first though. Cura 2.3 have a lot of awesome changes from previous versions, so you might be surprised :) Firstly: Thank you for interest and feedback. Always nice hearing from people using the instructables. :)Could you copy/paste your section with the temperature settings from your config file please?I would like to see the pin-assignments for the sensors.Which client program do you use for issuing Gcodes? I prefer Pronterface as it loads really fast, so nice for troubleshooting. I'm just using the config I list through my instructables. I use Cura 2.3 and no custom settings really. Shouldn't get too hot with fan on. I have mine under my cabinet case and it's just passively cooled with some air getting through 1cm gap under the casing.I have 0.85v on my XY, so yours shouldn't get too hot.. tried with different prints over 2 hours? No. You can only use Smoothieware on it, but if it freezes over 1-2 hours and it's doing it for more than just 1 file, I bet it is due to overheating.Have you tried measuring heat off the drivers or around the board? What is your voltage on drivers?Maybe the controller is placed inside the printer and gets hot? If my previous reply (from today/just now) doesn't pan out.. or maybe just start by doing it: contact MKS and/or the seller about the issue.. if it's hardware issue you want to let them know as soon as possible. Great. Glad it worked out :) I just googled it some and can see various people have experienced the same. Some from bad SD cards instead though. Don't worry about pronterface yet.Firstly please answer the first question as I can't track down faults with no information.Also please try the SD formatter I linked to. Windows and other OSs tends to mess up cardsWhich 2 files do you put on the SD card? You need to put on:firmware.bin andconfig.txtAfter you power printer off and on (also remove usb cable) you should have:firmware.curconfig.txtRegarding pronterface:Don't bother trying to connect untill you have the right files on the SD card as you just can't.Remember to specify the right COM port and BAUD rate.Does the Sbase show up as a com port when you connect it, and have you installed the windows drivers? I don't understand the difference between "FIRMWARE.CUR" and "firmware.cur" aside from you using capital letters?You want to use the firmware from Smoothieware and not from MKS:https://github.com/Smoothieware/SmoothiewareI use nightly build (edge) but you might want to use stable untill you know it works for you.http://triffid-hunter.no-ip.info/Smoothie.html Try using https://www.sdcard.org/downloads/formatter_4/ to format the card.Which 2 files do you put on the SD card? You need to put on:firmware.bin andconfig.txtAfter you power printer off and on (also remove usb cable) you should have:firmware.curconfig.txtHope it helps
{ "pile_set_name": "Pile-CC" }
#add_subdirectory(cartesian) add_subdirectory(noncartesian)
{ "pile_set_name": "Github" }
note cards/greeting cardsLetter writing is becoming a lost art. These beautiful blank cards will inspire you to revive that antique way of communication. Receiving a hand-written note will always brighten your day.
{ "pile_set_name": "Pile-CC" }
Over-expression of FRZB in gastric cancer cell suppresses proliferation and induces differentiation. Frizzled motif associated with bone development (FRZB) was a member of secreted frizzled related proteins (sFRPs) family. Previous evidences showed that FRZB played role in embryogenesis and diseases such as osteoarthritis and prostate cancer. The purpose of our study is to clarify the role of FRZB in gastric cancer cell proliferation and differentiation. The expression of FRZB in gastric cancer tissues were detected by immunohistochemistry. The expression of FRZB in eight gastric cancer cell lines and one immortal gastric epithelial cell GES-1 were detected by western blotting and real-time quantitative PCR. To investigate the role of over-expressed FRZB in gastric cancer cells, FRZB/pcDNA3.1 plasmid was constructed and transfected into gastric cancer cell line SGC7901. The changes of biological features in these stable transfectants were examined. FRZB was highly expressed in gastric cancer (90%), intestinal metaplasia (100%) and gastric dysplasia (90%), but no or just weakly (3/40) expressed in normal gastric mucosa. FRZB staining was stronger in intestinal-type gastric cancer tissues than that in diffuse-type ones and was positive correlated with differentiation grade. The expression of FRZB in eight gastric cancer cell lines was higher than in GES-1. Over-expressed FRZB inhibited cell proliferation in vitro and in vivo which was first caused by prolonged cell division progression in G2/M phase, and second by higher sensitivity to apoptotic inducing factors and spontaneous apoptosis. Our findings gave evidences that FRZB suppressed gastric cancer cell proliferation and modulated the balance between proliferation and differentiation in gastric cancer.
{ "pile_set_name": "PubMed Abstracts" }
1. Field of the Invention This invention relates to a system and method for molding parts, and more particularly, a system and method for molding parts from contaminated molding materials using a single thermal heat rise. 2. Description of Related Art In the field of thermoplastic molding, it is common to mold parts using either an injection or compression molding process. Due to the size of the orifices used in the injection molding equipment, it is often difficult to injection mold with reinforcing fibers, such as glass fibers, having a length over one-eighth inch because such fibers are not easily injected into or conveyed through the injection mold equipment. In addition, it is difficult to use contaminated molding materials such as those collected in plastics recycling programs unless they have been substantially cleaned, processed and put into a usable form and size prior to being used in the injection molding equipment. Such cleaning and processing are expensive and can substantially increase the cost of using the contaminated materials, thereby making them economically impractical. Another problem with the thermoplastic processes of the past is that the thermoplastics become degraded and lose, for example, their strength when exposed to multiple heat rises. In general, there are two basic types of compression molding processes which may be used for molding thermoplastics. First, a sheet molding process involves placing a reinforcement, such as a glass mat, between sandwiching layers of a thermoplastic and heating the materials to produce a single sheet of material. The single sheet of material is then cut to the desired size and then reheated to molding temperature before being placed in a compression molding press. This process has the disadvantage of higher cost because of the apparatus required, the material handling costs incurred in making the sheet, handling and cutting the sheet, and the like. The material used to make the sheet is also subject to three thermodynamic cycles, a first cycle when the thermoplastic sheet is formed, a second cycle when the thermoplastic sheets and glass mat are molded together, and a third cycle when the resulting sheet is heated to molten temperature prior to molding the part. The second form of thermoplastic compression is bulk molding compounds by producing a billet of molten material that is placed into a compression molding press which molds the molten material into a part. Effectively placing and distributing long reinforcing fibers in the billet has heretofore required complex machinery. For example, U.S. Pat. No. 5,165,941 issued to Ronald C. Hawley on Nov. 24, 1992, discloses an extruder apparatus and process for compounding thermoplastic resin and fibers. The Hawley extruder includes an apparatus for compounding thermoplastic resin and reinforcing fibers incorporating a resin extruder in which thermoplastic resin pellets are melted in a second, compounding, extruder in which the molten thermoplastic resin is mixed in intimate contact with long reinforcing fibers. The melted thermoplastic resin is not fed into the device with the fibers, but rather is introduced into the compounding extruder at a point downstream of the inlet point for reinforcing fibers, so that the fibers are mechanically worked and heated before coming into contact with heated, molten thermoplastic resins. The Hawley device generally suffers from complexity that raises the investment and maintenance costs. The compression molding of products using polymeric material and glass fibers has traditionally produced a material referred to as fiber glass reinforced plastic. This material exhibits characteristics better than the reinforced plastics, but does not exhibit strength, elasticity or impact resistance comparable to thermoplastic materials which are specifically designed to exhibit these characteristics. Most fiberglass reinforced plastic currently in the market is thermoset and is essentially a solidified mixture of fiber glass and plastic without benefit of chemical bonding or specific methods of enhancing polymer entrapment of the glass fibers because the glass fibers are merely immobilized in the resin in which it is embodied. In addition, thermoset materials are generally not recyclable other than as filler materials, while thermoplastic materials can be remelted and remolded. In the field of molded parts, many products are currently made from a variety of materials using moldable plastic. In the sporting goods field for example, bicycles, basketball backboards, toy vehicles and the like are commonly produced using multiple plastic materials. Compression molding has been a common method for producing basketball backboards and related parts of basketball goal assemblies, such as the support pull for the basketball backboard for many years. Heretofore, compression molding of basketball backboards and related parts has typically been limited to thermoset materials, which is characterized by placement of a cold charge in a compression mold. Thermoset process materials have certain drawbacks, including the fact that these material are generally not recyclable other than as filler materials. In general, there are two basic types of compression molding processes which may be used for molding thermoplastics. The following description of these two processes outline some of the difficulties that have prevented use of compression molding thermoplastics in the basketball goal assembly field. The first type is a sheet molding process that involves a reinforcement, such as a glass mat, between sandwiching layers of a thermoplastic and heating the materials to produce a single sheet of material. The single sheet of material is then cut to the desired size and then reheated to molding temperature before being placed in a compression molding press. This process has the disadvantage of higher cost because of the apparatus required, the material handling cost incurred in making the sheet, handling and cutting the sheet, and the like. The material used to make the sheet is also subject to three thermodynamic cycles, a first cycle when the thermoplastic sheet is formed, a second cycle when the thermoplastic sheets and glass mat are molded together, and a third cycle when the resulting sheet is heated to molted temperature before molding the part. A second form of thermoplastic compression is bulk molding compounds by producing a billet of molten material that is placed into a compression molding press which molds the molten material into a part. Effectively, placing and distributing long reinforcing fibers in the billet has heretofore required complex machinery as discussed in detail in parent application Ser. No. 08/220,906, now issued as U.S. Pat. No. 5,591,384. In addition, in recent years it has been increasingly common to provide graphics on the front face of molded parts, including the backboard, for a variety of reasons, such as aesthetic appeal to the consumer, product and source identification, and the like. However, the only commercially acceptable method of applying graphics have been silk-screened with inks or by applying decals. Silk-screening is time consuming and tends to fade after prolonged exposure to sunlight and the elements. Decals are also expensive and can peel off after time. An example of a prior art basketball backboard with silk-screen graphics is a backboard sold as xe2x80x9cShurShotxe2x80x9d. The silk-screen ShurShot backboard is believed to be about 48 inches across and mates a structurally foam polystyrene molded in a multiple-port injection process. The backboard is molded in the natural color of polystyrene, which is milky white. The entire ShurShot backboard is subsequently spray painted both to seal the polystyrene and to protect the backboard from ultraviolet radiation. Finally, graphics are silk-screened on the front face of the backboard. In some prior art applications, a graphics display was printed on a styrene sheet and laid by hand into a mold for forming the backboard. Alignment of the sheet was accomplished by aligning holes in the sheet on pins in the mold provided for producing the mounting holes in the backboard. Upon injecting styrene into the mold, the back portion of the graphics sheet melted to cause it to be joined to the face of the backboard. As styrene is relatively easy to print on, its use in this prior art process was conducive to the production of backboards provided with sheets having graphics printed thereon. One of the problems encountered with printing on parts or backboards molded using the system of the parent application Ser. No. 08/220,906 was that printing on polyolefin materials was difficult because the polyolefin-based materials were relatively non-porous and, therefore, not receptive to printing inks. What is needed, therefore, is an apparatus and method for molding thermoplastic parts which is simple and economical and which preserves the length of the reinforcing fibers, evenly distributes the reinforcing fibers or any other filler materials while maintaining flexibility of the material type in products fabricated, is capable of capitalizing on use of various contaminated thermoplastics to allow use of post consumer recycled material, and which provides a compounding and fabrication environment which promotes chemical bonding and molecular orientation to enhance the characteristics of the molded part. The foregoing also demonstrates the need for a compression molding apparatus and method for making parts, such as sporting goods equipment including basketball backboards from recycled thermoplastic materials without requiring the extensive cleaning and processing that heretofore has made use of thermoplastics for these products in practical. There is also a need to improve the in-mold graphics process to permit the basketball backboard and other plastic molded parts of basketball goal assemblies to be compression molded with thermoplastic resin materials having improved in-molded graphics. It is therefore a primary object of this invention to provide a method and apparatus which facilitates overcoming one or more of the aforementioned problems. In one aspect of the invention, this invention comprises a plasticator for creating a billet of moldable material including a feeder for receiving a plurality of molding materials comprising a predetermined amount of a polyester, other carbocyclic and reinforcing fibers and a suspender coupled to said feeder for receiving the molding materials, for creating a molten suspension of the molding materials without damaging a substantial number of the reinforcing fibers, and also for creating the billet. In one aspect of the invention, this invention comprises a plasticator for creating a billet of moldable material including a feeder for receiving a plurality of molding materials comprising a predetermined amount of a polyester, other carbocylics and reinforcing fibers, and a suspender coupled to the feeder for receiving the molding materials, for creating a molten suspension of the molding materials without damaging a substantial number of the reinforcing fibers, and also for creating the billet. In another aspect of the invention, this invention comprises a method for creating a billet for molding a part comprising the steps of (a) loading a plasticator with molding materials, the molding materials comprising a polyester, other carbocylics and reinforcing fibers, (b) heating the molding materials to a predetermined temperature, (c) blending the molding materials in order to create a molten suspension wherein a majority of the reinforcing fibers remain generally undamaged, and (d) extruding the molten suspension in order to form a billet having preselected billet characteristics. In yet another aspect, this invention comprises a plasticator for creating a billet from a plurality of molding materials, the plasticator comprising plasticating means for receiving the molding materials and for creating a molten suspension of the molding materials, and control means associated with the plasticating means for controlling the suspension characteristics applied to the molding materials in order to plasticity the plurality of molding materials into a billet having predetermined billet characteristics. In still another aspect, this invention comprises a system for molding a part comprising a plasticator for creating a billet from a plurality of molding materials, the plasticator comprising plasticating means for receiving the molding materials and for creating a molten suspension of the molding materials, control means associated with the plasticating means for controlling the suspension characteristics applied to the molding materials in order to plasticity the plurality of molding materials into a billet having predetermined billet characteristics, and a press having a mold for receiving the billet and for molding the billet into the part. In yet another aspect, this invention comprises a plasticating process comprising the steps of loading a plasticator with a plurality of molding materials, creating a mixture with the plurality of molding materials in the plasticator, and plasticating the mixture of the plurality of molding materials at a controlled temperature and pressure in order to create a billet having predetermined billet characteristics. In a still further aspect, the invention comprises a screw for use in a plasticator having a barrel, the screw comprising a root and a plurality of threads configured to permit a polyester, other carbocylics and a plurality of reinforcing fibers to be mixed to provide a billet having predetermined billet characteristics without damaging a substantial number of the reinforcing fibers. It is an object of this invention to provide a system and method for using long reinforcing fibers that can be loaded simultaneously along with the thermoplastics being used. Another object is to facilitate providing a system and method which is simple and economical and which provides a process that generally preserves the length of the reinforcing fibers through the plasticating and molding process. Another object of this invention is to provide a method and apparatus which evenly distributes any filler materials, such as reinforcing fibers, which are used in the apparatus and method. Still another object of the invention is to provide a method and apparatus which facilitates using contaminated molding materials which have heretofore been undesirable for use because of their contamination or because they are expensive to clean sufficiently for use. Still another object of this invention is to provide a method and apparatus which facilitates or enhances chemical bonding and molecular orientation of the polymer molding materials being used. Yet another object is to provide a system and method for efficiently and effectively in-molding graphics into a part such as a basketball backboard or other sporting equipment. In a still further aspect of the invention this invention comprises a plasticating process comprising the steps of loading a plasticator with a plurality of molding materials, creating a mixture with the plurality of molding materials in the plasticator, and plasticating the mixture of said plurality of molding materials at a controlled temperature and pressure in order to create a billet having predetermined billet characteristics. In another aspect of the invention a process for molding a part comprises the steps of placing a sheet into a mold prior to molding, placing a billet onto the sheet, compression molding the sheet and the billet to produce a part such that the sheet becomes integrally molded with the part. In another aspect of the invention a molded part comprising a compression molded part molded from a plurality of materials comprising a predetermined amount of a reinforcing fiber and thermoplastic polymers, a sheet integrally molded into said part, the sheet comprising a graphics side facing away from the part. In still another aspect of the invention a basketball backboard comprising a backboard member molded from a plurality of materials comprising a predetermined amount of a reinforcing fiber and thermoplastic polymers, and a sheet integrally molded into the backboard member, the sheet comprising a graphics side facing away from the part. These objects and others will be more apparent when the following description is read in conjunction with the claims and drawings.
{ "pile_set_name": "USPTO Backgrounds" }
Mario and lawege games Mario And Luigi Games. You searched for mario and luigi, we found the following search results from our collection of online games for you to play on. Luigi Mario games online free for kids to play, no download. Luigi Cave World 3 is a classic 2D platform game for kids, teens, and nostalgic grownups where. The first three games have the playable characters say "Nintendo!" when the game boots up (Mario and Luigi in ‎ Mario & Luigi: Superstar Saga · ‎ Mario & Luigi: Partners in Time. Mario and lawege games Video Evolution of Final Bosses in Mario & Luigi Games (2003-2017) Watch the game walkthrough. Super mario save luigi. He is manipulated once again when he is turned into Shrowser by the Elder Princess Shroob. The badges are part of a gauge that fills when an action command is executed well. Retrieved from " https: Super Mario Save Luigi Game Description. Partners in Time , beans are used to buy badges. Dream Teamwas announced during February 14, 's Nintendo Direct. Flash Super Mario Bros. The badges are part of a gauge bauernhof puzzle fills when an action command is executed. In battle, Mario and Luigi can attack either by using one of their basic attacks jumping or with a hammer or by using a special Bros. You need to install the Adobe Flash Player to play the game! New Best Games Best Of New. Each title has the player controlling Mario and Luigi to fight the antagonists. This game has a rating of 92 out of based on user ratings. Superstar Saga in the Action , Adventure , Arcade , Challenge , Emulator , Fighting , Funny , GBA , Mario , Miscellaneous , Platform , RPG , Skill , and Tricky gaming categories. Mario Tractor 2 Player. See our Mobile Games category for games compatible with tablet and mobile devices. When Princess Peach has traveled to the past, Princess Shroob manages to capture her, but not without Peach trapping the Elder Princess Shroob - the real leader of the shoobs - in the Cobalt Star. Super Mario Bros Star Scramble 2: Combine the power of Mario and Luigi to pull off a super special tag-team move and immerse yourself inside the bright, cartoonish, and humorous world. Much like Luigi, Baby Luigi is a more timid brother than Baby Mario. Galaxy online armor games on Social Media: Created from brewing 25 Chuckle Beans, the Chuckle Blend gives 4 SPEED to the brother that uses it. Fawful later gives Bowser a Vacuum Mushroommaking Bowser inhale everything around him, including Mario, Luigi, Princess Peach, and other characters. Bowser later reveals that he is merely using Antasma to advance his own schemes. Personal tools Not logged in Talk Contributions Create account Log in. In all games, she is kidnapped at some point. Play more games like Mario and Luigi: Enemies are encountered on the overworld, and the player can interact the enemy and enter into a battle scene. October 6, Nintendo 3DS. Mario and lawege games - Service ist As Bowser and Paper Bowser were arguing, Paper Bowser Jr. Paper Mario can create copies of himself to mitigate his low HP and attack multiple times at once. Although the storylines are similar to the story in game, there are multiple variations and twists. Superstar Saga , their stats elevate. When there is trouble, Mario attempts to solve the problem as quickly as he can, dragging Luigi alongside him. Grab all the coins to reveal the star.
{ "pile_set_name": "Pile-CC" }
Acute exposure of rabbit jejunum to ethanol. In vitro uptake of hexoses. The effect of acute exposure of rabbit jejunum to ethanol on the uptake of three hexoses was examined in vitro. With ethanol present in the preincubation medium for 30 min, or directly in the incubation medium for 6 min, glucose uptake was reduced. Kinetic analysis demonstrated that ethanol in the preincubation medium was associated with a rise in the value of the apparent Michaelis constant (Km*), whereas the inhibition of glucose uptake observed with ethanol present directly in the incubation medium was associated with a reduction in the apparent passive permeability coefficient (Pd*), a reduction in the maximal transport rate (Jdm), and an increase in Km*. When increasing concentrations of ethanol were added to the preincubation or to the incubation medium, there was a reduction in the uptake of both 1 mM and 40 mM glucose, galactose, and 3-O-methyl glucose. The addition of 40 mM galactose or 1 mM phloridzin to 40 mM glucose was associated with a 50% reduction in glucose uptake, but this uptake was not further inhibited by the addition of 6% ethanol (v/v). Similarly, the uptake of 3-O-methyl glucose was inhibited by the addition of 40 mM glucose or galactose but no further reduction in uptake was achieved by adding ethanol. Finally, galactose uptake was inhibited by adding 40 mM glucose or 40 mM 3-O-MG, but the addition of 6% ethanol was associated with no further decline in the uptake of galactose.(ABSTRACT TRUNCATED AT 250 WORDS)
{ "pile_set_name": "PubMed Abstracts" }
AcadeMir Charter School West has partnered with Sounds of Excellence School of Music and will now be offering after-school MUSIC LESSONS! This Thursday, December 15, 2016 at 6:00 p.m., there will be an orientation with the Sounds of Excellence School of Music owner to answer any of your questions and to give you more information on what’s starting in January!
{ "pile_set_name": "Pile-CC" }
Dismissed and Memorandum Opinion filed March 4, 2004 Dismissed and Memorandum Opinion filed March 4, 2004.   In The   Fourteenth Court of Appeals ____________   NO. 14-04-00095-CR ____________   CARL DENNIS FOSTER, Appellant   V.   THE STATE OF TEXAS, Appellee     On Appeal from the 182nd District Court Harris County, Texas Trial Court Cause No. 711,264     M E M O R A N D U M   O P I N I O N The trial court signed a judgment adjudicating appellant=s guilt for possession of more than four, but less than 200, grams of cocaine and sentencing appellant to confinement for thirty years in the Institutional Division of the Texas Department of Criminal Justice on June 29, 1998.  Appellant=s pro se notice of appeal was not filed until January 26, 2004.  The record before this court contains no indication that appellant was granted an out-of-time appeal by the Texas Court of Criminal Appeals. A defendant=s notice of appeal must be filed within thirty days after sentence is imposed when the defendant has not filed a motion for new trial.  See Tex. R. App. P. 26.2(a)(1).  A notice of appeal which complies with the requirements of Rule 26 is essential to vest the court of appeals with jurisdiction.  Slaton v. State, 981 S.W.2d 208, 210 (Tex. Crim. App. 1998).  If an appeal is not timely perfected, a court of appeals does not obtain jurisdiction to address the merits of the appeal, and it can take no action other than to dismiss the appeal.  Id. Accordingly, the appeal is ordered dismissed.   PER CURIAM Judgment rendered and Memorandum Opinion filed March 4, 2004. Panel consists of Chief Justice Hedges and Justices Frost and Guzman. Do Not Publish C Tex. R. App. P. 47.2(b).  
{ "pile_set_name": "FreeLaw" }
Zhou Xiaoping Zhou Xiaoping (born 24 April 1981) is a Chinese essayist and popular blogger. His most well-known works are Please Do Not Fail this Era!, Young, do you really know about this country?, Where did our heroes go?, and Nine Tricks of the United States Cultural Cold War. He is a supporter of communist party rule and has expressed nationalist, anti-American and anti-Western sentiment. Zhou is noted for praising by Communist Party General Secretary Xi Jinping at a conference on art and literature. Xi lauded Zhou for spreading "positive energy" in 2014.. Life Zhou was born and raised in Zigong, Sichuan, after junior high school, he started to publish works in 1996. "Cutlassfish Zhou"(周带鱼)became the nickname for his nationalist, pro-Communist, pro-Chinese government and anti-American writing. Zhou has been praised by General Secretary Xi Jinping for his "positive energy". Works Please Do Not Fail this Era! () Young, do you really know about this country? () Where did our heroes go? () Nine Tricks of the United States Cultural Cold War () References External links Category:1981 births Category:Writers from Zigong Category:Living people Category:Archibald Prize Salon des Refusés People's Choice Award winners Category:People's Republic of China writers Category:Chinese bloggers
{ "pile_set_name": "Wikipedia (en)" }
Carretera Costera Riviera Mayo Carretera Costera Riviera Mayo (Mayo Riviera Coastal Road) formerly known as Brecha de Sinaloa is a state road in the Mexican state of Sonora. It runs from Agiabampo to Yavaros. Route description As of January 2009 Mayo Riviera Coastal Road is a dirt road except the part running from the intersection to the road to Mexican Federal Highway 15 in Las Bocas to the beach of Camahuiroa. This part was opened in 2008. References Category:State highways in Sonora
{ "pile_set_name": "Wikipedia (en)" }
This invention relates generally to fuel burner control system and, more particularly, to a burner control system that utilizes a resistive heater element for igniting fuel emanating from a fuel burner. The continuing interest in reduced energy consumption and increased safety has resulted in the development of safer and more fuel efficient burner control systems. Of particular note has been the extensive replacement of pilot burner systems with systems employing electronic ignitors that are energized only when main burner ignition is desired. Such electronic ignitor systems eliminate the fuel loss entailed by pilot burners during periods in which full burner operation is not required. Spark ignitors and resistive heater elements are two common mechanisms utilized to ignite fuel in electronic burner control systems. Although spark ignitors exhibit a number of desirable characteristics, resistive heating elements have certain inherent features that offer unique operational advantages. For example, a resistive heater element can establish a larger thermal mass than a conventional spark ignitor and, therefore, can provide more reliable ignition of less than optimum fuel and air mixtures. In addition, the positioning of a resistive heater ignitor with respect to a burner is less critical than that required for an analogous spark ignitor. The object of this invention, therefore, is to provide an improved burner control system that employs a resistive heater element as a fuel igniting mechanism.
{ "pile_set_name": "USPTO Backgrounds" }
Nope failed...it wants libcurl.so.4.1.0 which I could only find with ssl support which then requires a host of extra libraries...getting silly I thought.....unless theres a non ssl libcurl.so.4.1.0 floating around. Nope failed...it wants libcurl.so.4.1.0 which I could only find with ssl support which then requires a host of extra libraries...getting silly I thought.....unless theres a non ssl libcurl.so.4.1.0 floating around. So the libcurl is a bit of a sticking point. I think the developer is using it for extra functions rather than ssl. I looked at the sources but many commands such as easy_curl_xxx were being called needing the newer version. And clive needs python......blah mike edit...could compiling libcurl.so.4.1.0 without ssl support be a possibility...might be useful for other apps..just a thought Well was suggested I put up my gui...it runs cclive (video) or wget (file) as appropriate and included the real gtklogfileviewer (renamed) cos the substitute is erm not good enough. Pop into /usr/bin Just for peeps to play with..I use it all the time...needs working cclive. 0.4.7 is considerably larger and 0.3.1 still handles you tube and google so I've hung onto that version myself. mike edit..added a v2 thats easier for multiple downloads and try different formats edit 2 cclive 0.3.1 added just for completeness.....it too needs the curl update edit 3 oops fixed v2 for spaces in file names... edit 4 just changed to latest one with relaid gui ...been using it for a while now. Just finishing a rewrite that neatens thing up a bit...will post after testing. Ok... put everything together...the one for 0.4.7 not fully tested but there's only 2 minor syntax changes anyway.... edit 5 Ok rewrite done and now added a better display of current downloads and the ability to choose and stop then from it. Since -c is used a stopped/killed download can be resumed by using the same address and destination name. edit 6 Ouch...spaces in names messing up wget detection so more wrestling with bash and hopefully fixed now..the 0.4.7 gui may work as is with the latest release but will be checking soon,....yes but some additional formats added...should be fine for 0.4.7 or 0.5.7 You cannot post new topics in this forumYou cannot reply to topics in this forumYou cannot edit your posts in this forumYou cannot delete your posts in this forumYou cannot vote in polls in this forumYou cannot attach files in this forumYou can download files in this forum
{ "pile_set_name": "Pile-CC" }
565 F.3d 308 (2009) Michael ROSALES, Petitioner-Appellant, v. Nathaniel QUARTERMAN, Director, Texas Department of Criminal Justice, Correctional Institutions Division, Respondent-Appellee. No. 09-70013. United States Court of Appeals, Fifth Circuit. April 14, 2009. *309 Gregory William Wiercioch, Texas Defender Service, San Francisco, CA, for Petitioner-Appellant. Carole Susanne Callaghan, Postconviction Litigation Div., Austin, TX, for Respondent-Appellee. Before DAVIS, BENAVIDES and STEWART, Circuit Judges. PER CURIAM: Petitioner Michael Rosales is scheduled to be executed Wednesday, April 15, 2009. On April 8, 2009, he filed motions in the Northern District of Texas for appointment of counsel to assist in clemency proceedings and for a stay of his execution. Rosales appeals the district court's denial of both motions for stay of execution and for appointment of counsel, asking us to reverse and to grant the motions. For the reasons set forth below, we AFFIRM the judgment of the district court. *310 I. BACKGROUND The procedural history of Rosales's case is as follows: In May 1998, Rosales was convicted and sentenced to death for the murder of Mary Felder, which occurred during the course of a burglary or robbery. On direct appeal, Rosales' conviction and sentence w[ere] affirmed by the Texas Court of Criminal Appeals ("TCCA"); the United States Supreme Court denied certiorari review. Rosales also sought state and federal habeas relief, both of which were denied. On April 7, 2004, less than one week before his scheduled execution, Rosales filed a successive state habeas application arguing that he is mentally retarded and thus his execution is barred by Atkins v. Virginia, 536 U.S. 304, 122 S.Ct. 2242, 153 L.Ed.2d 335 (2002).... On April 12, 2004, one day before his scheduled execution, the TCCA held that Rosales' application failed to "set out sufficient facts to raise a bona fide claim under Atkins" and therefore dismissed his application as an abuse of the writ and denied his motion for a stay of execution. Ex parte Rosales, No. 55, 761-02 (Tex. Crim App.2004). That same day, Rosales filed a petition for writ of certiorari at the United States Supreme Court as well as a motion requesting a stay of execution and authorization to file a successive petition for writ of habeas corpus in this court. While the Supreme Court denied his petition on May 17, 2004, this court had already granted his request for a stay of execution as well as his motion for leave to file a successive petition on April 13, 2004. On April 15, 2004, Rosales filed a motion in federal district court requesting the appointment of counsel, permission to proceed in forma pauperis, permission to file a skeletal petition, and expenses to retain an investigator and a mental health expert. The motion was granted on April 22, 2004. On May 21, 2004, Rosales filed his amended petition and attached affidavits or declarations from eleven different witnesses.... Rosales v. Quarterman, 291 Fed.Appx. 558, 559-60 (5th Cir.2008). After conducting an evidentiary hearing, the district court denied Rosales's petition. Rosales then moved this court for a COA. On August 19, 2008, this court granted Rosales a COA as to his Atkins claim out of "an abundance of caution." Id. at 562. The court concomitantly affirmed the district court judgment dismissing that claim. Id. at 563. The Supreme Court denied Rosales's petition for certiorari on February 23, 2009. Rosales v. Quarterman, ___ U.S. ___, 129 S.Ct. 1317, ___ L.Ed.2d ___ (2009). After the denial of certiorari, the presiding judge of the 364th Judicial District Court of Lubbock County, Texas, scheduled Rosales's execution for Wednesday, April 15, 2009. Therefore, under Texas law, any application that Rosales sought to make to the Texas Board of Pardons and Paroles Clemency Section ("Clemency Board") was due no later than March 25, 2009. See 37 Tex. Admin. Code §§ 143.43(a) (requiring the written application on behalf of a convicted person seeking recommendation of a reprieve from execution to be delivered to the Clemency Board no later than twenty-one calendar days before the execution date), 143.57(b) (requiring the written application on behalf of a convicted person seeking recommendation of commutation of death penalty to lesser penalty to be delivered to the Clemency Board no later than twenty-one calendar days before the execution date). Rosales did not file an application with the Clemency Board for either a reprieve of execution or commutation of his death *311 penalty prior to the deadline, nor does the record indicate that he has made any such request or filing to date. On Wednesday, April 8, 2009, Rosales filed motions for appointment of counsel and for stay of execution in federal district court, and the State filed its opposition to both. The same day, in a single-paragraph opinion, the district court stated that Rosales's motion should be denied "in all things," and cited to Harbison v. Bell, ___ U.S. ___, 129 S.Ct. 1481, 1486, 173 L.Ed.2d 347 (2009), which quotes the statutory language from 18 U.S.C. § 3599(e): "once federally funded counsel is appointed to represent a state prisoner in § 2254 proceedings, she `shall also represent the defendant in such ... proceedings for executive or other clemency as may be available to the defendant'" (emphasis added by district court). Although the district court did not elaborate on its reasoning, presumably the emphasis on "as may be available" indicates that the motions were denied because the court concluded that state clemency relief was no longer available because Rosales's deadline to file an application with the Clemency Board had passed. On April 9, 2009, Rosales appealed, and the parties completed their briefing the next day. II. DISCUSSION A. Application for Stay of Execution Rosales argues that the district court has the power to stay his execution to allow his new counsel time to prepare and make a filing with the Clemency Board under McFarland v. Scott, 512 U.S. 849, 857-58, 114 S.Ct. 2568, 129 L.Ed.2d 666 (1994). However, McFarland does not grant the district court or this court greater authority to stay an execution than is found in the statutory language of 28 U.S.C. § 2251, and Rosales's reliance on the case for a broad reading of the district court's power to issue a stay is misplaced. "Federal courts cannot enjoin state-court proceedings unless the intervention is authorized expressly by federal statute or falls under one of two other exceptions to the Anti-Injunction Act." McFarland, 512 U.S. at 857, 114 S.Ct. 2568. However, "[t]he federal habeas corpus statute grants any federal judge `before whom a habeas corpus proceeding is pending' power to stay a state-court action `for any matter involved in the habeas corpus proceeding.'" Id. (quoting § 2251) (emphasis added); see also Williams v. Cain, 143 F.3d 949, 950 (5th Cir.1998). The power to issue a stay of execution comes from § 2251, and the question is whether there is a pending or potential habeas corpus proceeding before the court. See Teague v. Johnson, 151 F.3d 291 (5th Cir.1998) ("once the appellate mandate issues, a habeas petition is no longer pending before the court of appeals, and we have no jurisdiction to stay proceedings under § 2251"); Williams, 143 F.3d at 950 (holding district court has no power under § 2251 to stay execution when there is no pending habeas proceeding); see also Howard v. Dretke, 157 Fed.Appx. 667, 670-72 (5th Cir.2005) (unpublished) (holding both the district court and this court lacked jurisdiction to grant stay of execution in conjunction with motion for appointment of counsel that was not tied to pending or proposed habeas proceeding in the district court, relying on the language of § 2251, Williams, and Teague). There is no dispute in this matter that no habeas petition remains pending in the federal courts. Therefore, both the district court and this court are without jurisdiction to enter a stay of execution. *312 B. Motion for Appointment of Counsel Rosales argues that he is entitled to appointed counsel to investigate and present his argument for clemency to the Clemency Board, pursuant to the recent holding of the United States Supreme Court in Harbison v. Bell, ___ U.S. ___, 129 S.Ct. 1481, 173 L.Ed.2d 347 (2009). In Harbison, the Supreme Court announced that 18 U.S.C. § 3599 authorizes federally appointed counsel to represent their clients in state clemency proceedings and entitles them to compensation for that representation. [O]nce federally funded counsel is appointed to represent a state prisoner in § 2254 proceedings, she "shall also represent the defendant in such ... proceedings for executive or other clemency as may be available to that defendant." § 3599(e). Because state clemency proceedings are "available" to state petitioners who obtain representation pursuant to subsection (a)(2), the statutory language indicates that appointed counsel's authorized representation includes such proceedings. 129 S.Ct. at 1486. Until the Harbison decision, this court's precedent denied appointment of federal counsel for post-habeas state clemency proceedings. See Clark v. Johnson, 278 F.3d 459 (2002). However, we do not read Harbison so broadly as to require the appointment of new counsel where the already-appointed counsel has never withdrawn from the case and is well familiar with the facts on which the petitioner claims his clemency petition should be based. Reviewing the record, attorneys were appointed counsel to Rosales in April 2004 to file a successive habeas petition containing his Atkins claim. As those attorneys have never withdrawn from the case, we agree with the State that Rosales had appointed counsel during the time in which he could have made an application to the Clemency Board. Moreover, in reviewing the papers submitted to this court, we note that there is no assertion made that there is any additional evidence in support of Rosales's Atkins claim beyond that which was presented to the district court and Fifth Circuit in his habeas proceeding. Rosales's motion asserts that there might be evidence of a pre-age eighteen onset of mental retardation to be uncovered with additional resources. But beyond that speculative assertion, he does not specify what evidence might be uncovered that was not discovered during his habeas litigation. Finding this case factually and procedurally distinguishable from Harbison, we find no abuse of discretion in the district court's denial of Rosales's motion for the appointment of counsel. III. CONCLUSION For the foregoing reasons, we AFFIRM the judgment of the district court.
{ "pile_set_name": "FreeLaw" }
Q: How to get count of post of each user by day on mongodb? How to get count of post of each user by day on mongodb? I have a similar dataset like below { "_id" : ObjectId("58863104f9881947d6d328c3"), "time" : 1484755908748, "user" : "mjt", "post" : "lorem ipsum...." }, { "_id" : ObjectId("58863104f9881947d6d328c3"), "time" : 1484755908748, "user" : "joe", "post" : "lorem ipsum...." } .... simple try I did but gave error db.collection.aggregate([ { $project: {user:1, isoTime : {$dayOfMonth : {$add : [new Date(0),"$time"]}} }}, {$group : {_id:"$isoTime", count: {$sum:1}}} ]) this gives error : "ok" : 0, "errmsg" : "can't convert from BSON type null to Date", "code" : 16006, "codeName" : "Location16006" A: You actually need to filter your collection for documents which have the time field (i.e. it is not null) and where the type is NOT a date and then group per user per day using the $dateToString operator which produces a formatted date time string that will represent the day. Run the following aggregate operation to get the count of posts per day db.collection.aggregate([ { "$match": { "time": { "$exists": true, "$not": { "$type": 9 } } } }, { "$group": { "_id": { "$dateToString": { "format": "%Y-%m-%d", "date": { "$add": [new Date(0), "$time"] } } }, "count": { "$sum": 1 } } } ]) And this pipeline should give you both the number of posts per user per day and the overall post count for that day: db.collection.aggregate([ { "$match": { "time": { "$exists": true, "$not": { "$type": 9 } } } }, { "$group": { "_id": { "user": "$user", "yearMonthDay": { "$dateToString": { "format": "%Y-%m-%d", "date": { "$add": [new Date(0), "$time"] } } } }, "count": { "$sum": 1 } } }, { "$group": { "_id": "$_id.yearMonthDay", "userCounts": { "$push": { "user": "$_id.user", "count": "$count" } }, "total": { "$sum": "$count" } } } ])
{ "pile_set_name": "StackExchange" }
Ibrutinib has the following structure, with a chemical name of 1-[(3R)-3-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one Ibrutinib is the first in class of an oral Bruton's tyrosine kinase (BTK) inhibitor for the treatment of chronic lymphocytic leukemia (CLL) and is one of the first medicines to file for FDA approval via the new Breakthrough Therapy Designation pathway. Ibrutinib forms a covalent bond with a cysteine residue (Cys-481), leading to irreversible inhibition of BTK, thus effectively blocking the transfer of cancer cell from B-cell to lymphoid tissue where is benefit for the growth of tumor. The intermediate compound having the following structure is employed to synthesize ibrutinib. The compound of formula VI can be used to produce ibrutinib according to the method disclosed in America U.S. Pat. No. 7,514,444, and its synthesis route is depicted as below: The current methods for preparing the compound of formula VI are confined to two routes published in America U.S. Pat. No. 7,514,444, which can be represented by the following two routes: Route 1: Route 2: Hence, it is necessary to develop new preparation methods for the industrial production.
{ "pile_set_name": "USPTO Backgrounds" }
Esophagectomy without thoracotomy. It should be understood that esophagectomy without thoracotomy is not a surgical procedure for the treatment of a particular esophageal lesion but is only a surgical aid. Therefore, it is extremely important to discuss the specific indications for using this technique to treat a particular esophageal disorder. The technique of esophagectomy without thoracotomy should not be used for malignant lesions of the thoracic esophagus except under particular circumstances, such as resection of a carcinoma in an extremely early stage or palliative resection of advanced carcinoma of the thoracic esophagus without local invasion. Esophagectomy without thoracotomy is extremely useful for the treatment of esophageal or esophagus-related lesions, such as hypopharyngeal carcinoma, benign stricture of the esophagus, or even some carcinomas of the lower esophagus and cardia of the stomach.
{ "pile_set_name": "PubMed Abstracts" }
Association of the serotonin transporter promoter polymorphism with smoking behavior among adolescents. Serotonin transporter promoter polymorphism (5-HTTLPR) genotype was previously found associated with smoking behavior, difficulty in quitting smoking, and nicotine addiction; with non-replicated findings and contrasting results. Aim of the present study was to evaluate the possible association between 5-HTTLPR genotype and smoking behavior among adolescents, in relationship with psychological characteristics. Two hundred and ten Caucasian high school students (aged 14-19 years); 103 non-smokers, who have never smoked nicotine; and 107 tobacco smokers have been genotyped. Aggressiveness levels and temperamental traits were measured in both smokers and non-smokers, respectively, utilizing Buss-Durkee Hostility Inventory (BDHI) and Cloninger Three-Dimensional Personality Questionnaire (TPQ). Data about school performance have been also collected. The short-short (SS) genotype frequency was significantly higher among smokers compared with non-smokers (P = 0.023). The odds ratio for the SS genotype versus the long-long (LL) genotype frequency was 1.17 [95% CL (0.30-2.05)], when smokers were compared with non-smokers. The SS genotype frequency was significantly higher among heavy smokers with early onset, compared with moderate smokers with late onset (P = 0.042). BDHI irritability scores, NS scores at TPQ, and school failure frequency were significantly higher in smokers than in non-smokers. Multivariate model-fitting analysis evidenced a significantly greater relationship of genotype with irritability levels (BDHI scores) (0.34, P < 0.001) and temperament traits (NS scores) (0.36, P < 0.001), than with school performance (rate of school under-achievements) (0.18, P < 0.05) and nicotine smoking (number of cigarettes) (0.24, P < 0.01). Accordingly, factor-analysis showed that gene polymorphism contributes more directly to BDHI scores and NS scores (0.73; 0.71) than to smoking behavior and school under-achievement (0.54; 0.51). Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to "S" promoter polymorphism, may be associated with smoking behavior among adolescents and increased risk to develop nicotine dependence, possibly in relationship to personality traits, temperamental characteristics, and school under-achievements.
{ "pile_set_name": "PubMed Abstracts" }
We continued biochemical studies of mammalian DNA replication proteins. cDNAs for rat and human beta-polymerase have been subcloned in expression vectors, and the proteins have been overproduced in E. coli, purified in mg quantities, and sequenced. Structure-function aspects and in vitro DNA repair activities of the recombinant enzymes are being studied. Genomic DNA spanning the gene for human beta-polymerase was further characterized. The promoter region was studied by detailed deletion and site-directed mutagenesis using a transient expression system for assay. In other work, we purified and characterized a transcription factor for the human beta-polymerase gene. In vitro transcription studies of the gene are under way, as well as physical biochemical studies of the sequence-specific binding between the promoter and the purified factor. Studies of cell lines carrying inducible beta-polymerase mRNA antisense transcripts revealed that down regulation of beta-polymerase expression is associated with a block in DNA repair after nitrogen mustard treatment of cells.
{ "pile_set_name": "NIH ExPorter" }
Q: \hrule\hskip stretchability This \documentclass[12pt]{report} \def\usrf{\leavevmode\leaders\hrule\hskip 0pt plus 1em minus 0pt\kern 0sp} \begin{document} \noindent A\usrf{}B C\linebreak DEFGH \end{document} results in that where the "underscore" between A and B is way longer than 1em. How can I limit the maximum length of the \hrule, and why does it not work with the glue "stretchability" as given? A: You are telling TeX to stretch a line to the line width, so it will obey your order. Let's see a simpler example (plain TeX): \hbox to\hsize{A\leaders\hrule\hskip 0pt plus 1em minus 0pt B C} \noindent\the\badness \bye You get The value printed by \the\badness is the badness of the last typeset box. Indeed, the terminal will also show Underfull \hbox (badness 10000) detected at line 1 \tenrm A B C As soon as a glue has nonzero stretchability, it will stretch as much as required, at the expense of badness. Just like it happens to the glue between B and C. If you change the first line to \setbox0=\hbox to\hsize{A\leaders\hrule\hskip 0pt plus 1em minus 0pt B C} \showbox0 you'll find, in the log file, \hbox(6.83331+0.0)x469.75499, glue set 38.11542 .\tenrm A .\leaders 0.0 plus 10.00002 ..\rule(0.4+0.0)x* .\tenrm B .\glue 3.33333 plus 1.66498 minus 1.11221 .\tenrm C so the glue stretch ratio is 38.11542; this means that the first glob of glue (from \leaders) will become 38.11542 * 10.00002 = 381.15496 point wide and the second glob will become 38.11542 * 1.66498 = 63.46141 point wide. Can I state “stretch at most X”? No, because of the rule above. With some computations it is of course possible.
{ "pile_set_name": "StackExchange" }
Fast transient transistor simulation programs are important aids in computer aided design (CAD) of very large scale integrated (VLSI) circuits. A fast transient simulator differs from accurate circuit simulators like SPICE in its ability to simulate very large circuits at significantly higher speed, at the expense of some accuracy. Fast transient simulators provide the ability to simulate at transistor level circuits containing hundreds of thousands of transistors with high speed on the orders of hundreds time faster than accurate circuit simulators such as SPICE. The goal of fast transient simulators is to compute waveforms of voltages at circuit nodes and currents through circuit elements. Fast transient simulators are used when it is required to simulate circuits at an accuracy higher than that can be achieved by gate and switch level simulators, and with a speed higher than SPICE-like simulators. Fast transient simulation of a Metal Oxide Semiconductor (MOS) transistor circuit usually partitions the given circuit into D.C. connected components (DCCC). Each MOSFET model is cut across its transistor gate. The interaction between partitions is simplified by considering only the dependence of MOSFET channel current on its gate voltage. Each partition is simulated independently for a short time interval called the time step. During this time interval, it is assumed that all voltages at the boundary nodes of the partition are known. Usually they are computed through linear approximation, by interpolation and extrapolation. Based on such simplifications, the behavior of each partition is simulated independently for some short time interval called a time step. Time steps can be different for different partitions and they can vary during simulation for getting the desired trade-off between speed and accuracy. The partitions that do not change their state or change it slowly are evaluated with much longer time steps. This technique improves simulation speed as compared to traditional transistor level circuit simulators like SPICE. Because of the partition mechanism and the use of different time steps, the time points at which the simulator recomputes the states of the partitions are different for each partition. The simulator arranges reevaluation of partition states in an event driven manner. The simulator plans reevaluations of partition states according to its internal processes and changes of voltages at the partition boundary. For this purpose, it uses an event queue where it schedules partitions for reevaluation. From this queue, the simulator gets partitions for reevaluation according to their time schedule. The accurate behavior of each partition is described by a system of non-linear differential equations. One of the most accurate techniques to simulate the behavior of non-linear circuits is to use a modified nodal analysis for computing the system of equations, trapezoidal or backward Euler integration algorithm for their numerical integration, and Newton-Raphson iterations for computing voltage and current values at each time point. Such an approach is common for implementing accurate circuit simulators like SPICE. In order to get higher simulation speed, this technique is simplified in many ways. For example, the forward Euler integration algorithm can be applied, or the Newton-Raphson iterations can be substituted by approximate linearization of non-linear elements at each time point. Any type of simplification is at the cost of accuracy of the simulation results. Fast simulators differ among themselves in their selection of trade-off between speed and accuracy. For simulating partitions, fast circuit simulators similar to traditional SPICE-like circuit simulators require a model of MOS transistors. For SPICE simulators, an accurate transistor model is specified by very complex formulae for computing currents and charges of each transistor terminal as a function of terminal voltages. Computation of these complex formulae significantly slows down circuit simulation. In order to have high simulation speed, fast transient circuit simulators usually use a simplified transistor model. The simplified transistor model can be either analytical or table-based. Analytical models are usually not accurate enough for submicron short channel MOS transistors. Table models usually are able to provide much higher accuracy with higher computation speed. In the simplest straight forward approach, a table model is a collection of tables, each of which provides values of transistor terminal currents or charges as functions of terminal voltages. The tables are usually computed by using an accurate transistor level simulator like SPICE. The structure of a conventional bulk MOS transistor 10 is shown in FIG. 1. Transistor 10 has a substrate 12, a gate oxide 14, a gate 16, a drain 17 and a source 18. The electrical model 34 of transistor 10 is shown in FIG. 2 and has four terminals: a drain 37, a source 38, a gate 36 and a substrate 39. Therefore, a straight-forward model approach results in four charge tables and four current tables. Each of the tables has four arguments or inputs, viz. the four terminal voltages. Unfortunately, tables organized in such a manner are too large to use efficiently in any simulator. Therefore, fast transient simulators use different techniques to simplify their table models. The first simplification comes from the fact that transistor behavior does not change if we change all terminal voltages by the same value. In other words, transistor behavior is invariant to voltage shift. This simplification allows a reduction in the number of table arguments by one as one of the four terminals can be treated as a reference terminal. Other facts that are used for model simplification are charge and current conservation laws. The conservation laws make it sufficient to have models only for three terminal currents and charges and allow computation of the current and charge of the fourth terminal so that total charge and current ate zero. Unfortunately, these simplifications are not enough to make transistor models sufficiently efficient. Therefore, fast transient circuit simulators often use additional approximations for simplifying a transistor table model. For bulk MOS transistors, it is common to assume that transistor terminal capacitances are linear, meaning that they do not depend on transistor terminal voltages. This assumption permits using just average values of transistor terminal capacitances instead of a table of terminal charges as functions of terminal voltages. Currents of bulk MOS transistor table models can be simplified by ignoring substrate and gate currents as they are orders of magnitude less than transistor channel current and do not affect circuit behavior drastically. Simulators can simplify the model of bulk transistor channel current by considering the channel current as a function of two variables: (1) the voltage between drain and source and (2) the effective gate voltage. The effective gate voltage is defined as a difference between gate-to-source voltage and a threshold voltage, predetermined for each transistor. Threshold voltage is considered as a function of body voltage and may be modeled by a separate one-dimensional table. This approach follows from the simple analytical model of a bulk MOS transistor. Thus, instead of one three-dimension table for channel current, two smaller tables are used: one two-dimensional table and one single-dimensional table. Such table reduction costs some accuracy of the model. For pure digital MOS circuits, especially for CMOS circuits, the foresaid reduction still retains sufficient accuracy and allows the simulator to compute good approximation of circuit delays and power consumption. However, this model is not accurate enough for many circuits, for example circuits using many pass gates, circuits having very large D.C. connected components, and circuits that are very sensitive to accuracy, such as the PLL (Phase Locked Loop) circuits. Additional challenge and problem for fast circuit simulation are SOI circuits that are becoming more and more popular in high speed and low power VLSI designs. The structure of an SOI MOS transistor 20 is shown in FIG. 3. An SOI transistor is similar to a bulk transistor but it is manufactured on an insulator layer and completely isolated from one to another by the same insulator. SOI transistor 20 has a substrate (backgate) 22, a buried oxide 24, a body 26, a gate oxide 27, a gate 28, a source 29, a drain 30 and a shallow trench isolation 32 around the perimeter. Because of the SOI structure, transistor capacitances are much smaller than the ones in a comparable size bulk transistor. The reduced capacitances make an SOI transistor significantly faster and reduce power consumption. Thus SOI transistors are very attractive for high performance and low power circuits. SOI transistors also have other benefits like latch-up immunity, lower radiation susceptibility, etc. Unfortunately, designing VLSI circuits with SOI transistors is more difficult than with bulk transistors because SOI transistors have more complicated behavior than bulk transistors. In bulk transistors, the fourth terminal is a VLSI substrate that is permanently connected to ground or a supply voltage VDD. The counterpart terminal in an SOI transistor is a body that has very small capacitance and usually is not connected to any other circuit node. Because of that, the body potential (voltage) varies significantly during circuit operation due to such effects like capacitive coupling with other circuit nodes, leakage, and impact ionization currents. These effects significantly influence SOI transistor behavior by changing its threshold voltage. Another complication with the SOI transistor model arises due to its usage with different types of body connections. The most common case, and also the most difficult to simulate, is the floating body configuration wherein the transistor body is not connected to any other circuit node. The floating body type SOI transistor configuration provides the smallest transistor area but makes its behavior less predictable. The potential of a floating body can vary due to variation in the switching frequency, thus giving rise to an effect known as the history effect. This effect makes logic gate delay depend on gate switching history. Another type of SOI MOSFET configuration has its body and source connected together that makes its behavior similar to a bulk MOS transistor. An example of this configuration is illustrated in FIG. 4 wherein a structure 50 has an SOI transistor having an n+ drain 52, a gate 54, an n+ source 56 and a p+ tie 58 to tie the body with the source 56. The third type of SOI transistor configuration has a separate body contact that can be connected to any node of the circuit. An example of this configuration is illustrated in FIG. 5 wherein a structure 60 has an SOI transistor having an n+ drain 62, an n+ source 64, a gate 66 and a p+ body contact 68. Thus, transient simulators of SOI circuits should handle all these three types of transistors. The electrical model of an SOI transistor is shown in FIG. 6. SOI transistor 40 has five terminals as compared to four terminals of a bulk MOS transistor. Transistor 40 has a gate 42, a drain 44, a source 45, a body 46 and a backgate (substrate) 48. The additional terminal makes an SOI model significantly more complex and results in significant increase in model's table size. Simulation of SOI circuits is more sensitive to numerical errors because the history effect has a very large characteristic time constant as compared to logic gates' switching time. Even small numerical errors in body charge computation are accumulated resulting in prediction of wrong circuit delays. Because of that, accurate transient circuit simulators simulate SOI circuits much slower than bulk circuits that makes circuit design with SOI transistors even more difficult. Skilled artisans appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help improve the understanding of the embodiments of the present invention.
{ "pile_set_name": "USPTO Backgrounds" }
![](amjdentsci81885-0023){#sp1 .51} ![](amjdentsci81885-0024){#sp2 .52}
{ "pile_set_name": "PubMed Central" }
[Carotenoids as components of dietary supplements recommended for smokers and persons passively exposed to cigarette smoke]. Smoking is a very common addiction and a reason of many serious diseases of cardiovascular, respiratory and digestive systems and also a cancer. Active and passive smokers are exposed to nicotine and many carcinogenic products of tobacco smoke. Carotenoids (e.g. beta-carotene, lycopene) as natural, plant-derived antioxidants may decrease a risk of diseases connected with smoking. In accordance with literature, low level of carotenoids in blood plasma of smokers was observed and diet supplementation by carotenoids may compensate their deficit. However there are some reports in the literature that supplementation by high doses of beta-carotene may be dangerous for smokers.
{ "pile_set_name": "PubMed Abstracts" }
Trends in hepatitis B and hepatitis C virus among blood donors over 16 years in Turkey. We document in the present study the trends over the sixteen years in HBV and HCV seroprevalence among blood donors in Turkish populations. In this study, serologic test results of whole blood (n = 6.240.130) donors at 22 Red Crescent Centers between 1989 and 2004 were evaluated retrospectively. The overall prevalence was 4.19% for HBsAg and 0.38% for HCV antibody during the study period. The annual prevalence of HBsAg gradually increased from 4.92% in 1989 to 5.23% in 1991 (p=0.001, t=21.00, CI(95), 17237-22490) and gradually decreased from that to 2.10% in 2004 (p=0.001, t=17.27, CI(95), 12869-21342). The seroprevalence of HCV antibody gradually increased from 18 per 10.000 in 1996, to 56 per 10.000 in 1998 (p=0.073, t=3.81, CI(95), 459.62-5721.23), while that decreased to 34 per 10.000 in 2004 (p=0.021, t=7.49, CI(95), 743.98-3980.11). The seroprevalence of hepatitis B and C has decreased markedly between 1989 and 2004 in Turkey. This could be related to the significant increase in the number of volunteer blood donors that increased from 135,779 to 197,815.
{ "pile_set_name": "PubMed Abstracts" }
Hyperlinks in GNOME terminal how to benefit from fancy hyperlinks in your terminal... Over the years I’ve learned about many of the advantages of using a modern terminal and shell. I’m talking about using bash with GNOME terminal on a modern GNU/Linux distribution. I particularly like switching between the terminal and GUI applications. It’s now even better. Automatic Hyperlinks Occasionally, some program running in your shell might output what looked like a link: gnome terminal and vte will automatically add links to text that looks like a web hyperlink or an email address They can be seen when you hover over them, and a right-click will display a useful context menu: the terminal detected this text sequence as an email address, and the dialog makes it easy to open your MUA This was always useful, but detection was always a heuristic. In many situations it might show a hyperlink unnecessarily or omit one that would have been useful. Integrating Hyperlinks With recent versions of VTE this is now done properly, without needing a heuristic! Here’s what it might look like: the ls program can automatically add relevant links All this magic works because programs can include magic “escape codes” which tell the shell to do special things. They have been traditionally used to add colours or underlining to shell output. In this case they’re been used to send a special message telling the shell that it might want to hyperlink something. The venerable ls program was updated to include a --hyperlink option, which, when active produces the above output. If you look closely, it puts a fine line of dots over any such link. I chose to make this automatic, so I’ve added an alias that includes this by default, and other options: $ alias ls alias ls = 'ls -FGh --color=auto --hyperlink=auto' When you right click on one of the above links, it now shows a helpful menu: this is some magic that opens things in the right program I suspect that it uses xdg-open to run the correct program. In my case it causes folders to open in nautilus , images in eog , and pdf’s in evince . This isn’t limited to ls . A bunch of other programs have started to add this feature in various ways. A recent release of systemd has even added support for this in the systemctl status output. Future Work It’s now time to add useful contextual information to more of the terminal apps out there. Imagine having a git log with clickable sha1 hashes, or pasted irssi links which shorten and ellipsize, but which are still clickable? All of these things are possible, so start getting those patches upstream! Advanced Use Cases I started to think about if some fancier use cases were possible. Imagine if running an ls command over ssh could have the hyperlink information modified by the local shell so that it knew it was a remote URL. In that case, the terminal might consider converting it to a gvfs link instead, giving you easy access to remote files. It might be fun thinking about if adding hyperlinks to vim could offer links to full screen help dialogs. An even fancier idea might be to include a link to a trusted execution agent which could open up a GTK+ dialog, and send the response back to some socket that the program is listening on. The emacs and mutt users could have an easier way to view graphical email attachments. As we blur the lines between working in graphical environments and the terminal, power users who aren’t afraid of the shell only get more proficient. Fancy $PS1 Some of you might remember my earlier, $PS1 , hacks. I’ve decided to add a little more magic on to it. In my ~/.bashrc , in my ps1_prompt function, that runs and sets the $PS1 as part of my PROMPT_COMMAND , I added a little snippet: # get the url encoded version of URI on each PS1 display local encoded = " $( urlencode 'file://' ) \h $( urlencode ` pwd ` ) " local W = '\[\033]8;;' " ${ encoded } " '\a\]''\w''\[\033]8;;\a\]' # thanks purpleidea! This builds a special hyperlink for the displayed path. I had to use the pwd hack to get the working directory, because the \w and \W variants both ellipsize the path, and include the tilde ( ~ ), which would disrupt the expected path format. The URI needs to be safely encoded, and the urlencode function that I used is: # urlencode <string> # TODO: suggestions and improved versions are welcome! function urlencode () { local length = " ${# 1 } " for (( i = 0 ; i < length; i++ )) ; do local c = " ${ 1:i:1 } " case $c in [ a-zA-Z0-9.~_- ]) printf " $c " ;; * ) printf '%s' " $c " | xxd -p -c1 | while read c; do printf '%%%s' " $c " ; done ;; esac done } My full $PS1 now looks like: # all on a single line w/o newline (this might wrap due to the space at the very end) PS1 = " ${ debian_chroot:+($debian_chroot) } [email protected] \h:\[\033[01;34m\] ${ W } \[\033[00m\] ${ ps1_git }${ ps1_status } " (Please note that some portions of this are not included here. See my earlier PS1 blog posts for more information.) here's a screenshot of what this looks like showing a tooltip on mouseover (the mouse pointer is hidden in this screenshot) Now I can click to cause the path to open in nautilus . I previously used the nautilus . command to cause this to happen, and while I probably still will to avoid the context switch-over to the mouse, it’s a nice little addition which I think is pretty neat. It also gives me some extra material for this article. Understanding The Escape Sequences If you’d like to understand why there are additional \[ and \] sequences in the above local W= , that’s because bash needs to know how to wrap the text in the shell output. It’s not smart enough to know which characters are visible (and that should take up space) and which ones aren’t, so in order to tell it, you must wrap the “non-printing” (invisible) characters with those special open and close sequences so that all the math works out as intended. If you don’t, you’ll see a weird mess of characters when you resize your terminal or use tab completion. Remove them and see for yourself! Inside each of those sequences of characters, you’ll first see a: \033]8;; followed by the encoded URL, and then a closing \a in quotes. That’s because \033 is the magic way to write ESC , and the start code is ESC ] . It all ends with a BELL character which is an \a . Inside of that we have the magic number 8 , which means that we want to use the hyperlink feature, and it includes a custom pattern which is that ;; part. This can include a URI to begin the location of a hyperlink, and omit it inside another magic 8 sequence to close it. Inside the ;; you can include some special params if needed. For more information on this, you can review the ANSI escape codes. Information about which other applications are tracking this feature is available here. Conclusion Hope you enjoyed this. Hopefully you can add some hyperlink integrations to your application today! Can you think of any other types of magic escape codes we should add? Thanks to xmby in #bash for helping me understand some of the shell escape code nuances. Happy Hacking, James You can follow James on Twitter for more frequent updates and other random thoughts. You can support James on Patreon if you'd like to help sustain this kind of content.
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A. Harmsworth Glacier A. Harmsworth Glacier or Alfred Harmsworth Glacier () is a glacier in northern Greenland. Administratively it belongs to the Northeast Greenland National Park. The glacier was named by Robert Peary after British newspaper magnate Alfred Harmsworth, who had gifted him expedition ship "Windward" following a lecture on Polar exploration Peary gave at the Royal Geographical Society in 1897. Geography The A. Harmsworth Glacier is flowing roughly to the NW and has its terminus at the head of the Benedict Fjord. It fills most of the inner fjord. It has a velocity of per year. The peaks of the Roosevelt Range rise on both sides and at the head of the A. Harmsworth Glacier. To the east some peaks rise to heights above . The A. Harmsworth Glacier is one of the large glaciers in the area. See also List of glaciers in Greenland Peary Land References External links 83° 35' 56" N 36° 47' 32" W Fjord Gletcher. The northernmost calving glacier Category:Glaciers of Greenland
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Q: Learning functional programming after other programming paradigms I have taught myself C, Python, Java and a few other procedural or object oriented languages to an intermediate degree from resouces on the internet (thanks SO :D) and in books. When I tried to learn Haskell, I couldn't wrap my head around what the code actually did. Is there a better functional language for someone coming from a background in procedural or object oriented programming to learn? Are there any resources meant for people in my situation? Thanks! A: It's probably varies with people (and this question is bound to get closed over that), but the way I see it: there isn't a stair you need to step on before you can be within reach to Haskell. So I'd say you're not driven temporarily off necessarily by the language, but by your sources of learning. For the only truly gentle introduction, I recommend LYAH. It keeps things within reasonable difficulty and it has some really entertaining points every now and then. However, if you still want to almost-soften your transition, you can check out F# which isn't a functional language but it will give you a good taste of FP, and it will be very familiar to you because you still live in an OO world. You can also check out basically any other functional language and it will give you some of the mindset (Scala, ML, etc.). Keep in mind that I say "almost-soften", because Haskell is very different (especially because of purity), and that gives you a very logical and mathematical mindset to things and that has been very different for me than any other language I learned. It's incredible. It was much beyond learning different syntax, it's a way to think about things and I can always find myself learning more and a truly amazing part of it is that (since it's so logical, mathematical, reasonable, etc.) the new ways of thinking I acquire with Haskell don't leave me both when I use other languages and even in my personal daily life. That being said, the only thing truly horrible with Haskell is that it ruined me for other languages. I used to like C#... :(
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CREATE ACCOUNT FORGOT YOUR DETAILS? PakistanCriminalRecords.com is a free research resource being provided free of charge by managed by Background Check Pvt Ltd, one of the Asia's largest screening firms, to public for the awareness about the serious and organized crime in Pakistan. Quetta: 2 bodies found, man shot dead Quetta: 2 bodies found, man shot dead QUETTA: A man was killed on the provincial capital’s SariabRoad and twomutilatedbodies were found in Lasbeladistrict on Thursday. Police said armedmen on a motorbikeopenedfire on a man near Irrigation Colony in Quetta, leaving him injured. Identified as AhmedAli, the man was taken to hospital where he died. A case was registered against unidentifiedkillers. Two mutilated bodies were found in Bela tehsil of Lasbeladistrict. Levies Force sources identified the bodies as that of BahadurKhan, a resident of Kharandistrict, and Rashid of Quetta.
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In the first of a series of guest editorials for Kayfabe News, self-described “sports entertainment superfan” Vance Kenneth MacManus explains why he believes WWE’s flagship program, Monday Night Raw, should be an hour longer. As a life-long member of the WWE Universe®, I cannot wait to watch WWE Raw every Monday night on the USA Network. Quite frankly, it is the highlight of my week! Like each and every one of you, I look forward to watching the WWE Superstars® and Superstarlets compete inside the squared circle. Anything can happen in WWE! Quite frankly, WWE brings smiles to people’s faces — including my own! When I’m watching WWE’s captivating weekly live events and biweekly pay-per-views — whether at home, sculpting my preposterous physique at the gym, or flying aboard my private jet — I can’t help but admire the creative genius and business savvy that has made WWE an international juggernaut. But, quite frankly, I have one complaint: I just wish Raw were longer! Three hours is just not enough time for WWE to put enough smiles on enough faces each Monday! As a superfan, I just need more time to watch my favorite Superstars®, like Roman Reigns, Seth Rollins, and Roman Reigns! If Raw were four hours long, it would give me the time I need to fully appreciate Raw, which is the longest running weekly episodic program in television history! Longer episodes of Raw would also give me more time to appreciate the valued sponsors that help WWE create such captivating programming, and would give me more more time to buy amazing fashions and other radical products on WWEShop.com®! So if you feel like I do, why not use the hashtags #FourHourRaw and #ThankYouVince on social media, and perhaps WWE executives will listen to us fans, the way they always do! Perhaps, if we’re lucky, SmackDown LIVE® will get longer too! Sure, I’m just a fan like each and every one of you, but make no mistake about it — together we can make our voices heard, quite frankly. – Vance Kenneth MacManus Quite frankly, you need to subscribe to our YouTube Channel, quite frankly
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Mail piling up early in state legislative races AUGUSTA, Maine — Need a sign that the battle for control of the Maine Legislature is intensifying? Look to your mailbox. If you live in a select handful of state Senate and House districts, you’re probably seeing the result of nearly $375,000 the state’s Democratic and Republican parties have spent on political mailers since mid-August in an effort to win legislative seats that ultimately could decide which party controls the House and Senate chambers. In the last two weeks alone, the two major parties have pumped more than $220,000 into mail pieces — about $137,000 from Democrats and nearly $85,000 from Republicans — that expressly support or oppose the election of House and Senate candidates, according to expenditure reports filed with the Maine Ethics Commission. For the Senate, a half dozen races appear to have most consistently attracted the parties’ attention in recent weeks. The list of House races is considerably longer. By this point in 2010, the parties hadn’t even started spending their funds on mail pieces specifically supporting or opposing the election of legislative candidates. At this point in 2008, the state’s Democratic party had spent only $4,700 on a mail piece supporting a single Senate candidate, according to Ethics Commission records. Story continues below advertisement. “To me, the conclusion one can draw based on the level of spending so far is that everybody recognizes that control of both chambers is up for grabs and that it’s going to be a close election,” said Josh Tardy, a former House Republican leader who directed legislative campaigns. And while the parties together have recorded $375,000 in spending on legislative campaign mailers so far, that number doesn’t offer a complete picture of the total amount parties have spent on legislative campaign mail. That’s because if third-party campaign mailers don’t expressly advocate for or against a candidate’s election, political parties and outside groups aren’t required to report them to the Maine Ethics Commission within two days of making the expenditure until the final 35 days of the campaign. Quarterly campaign finance reports due next week will offer additional insight into what the parties have spent to mail out their messages. While the Maine Republican Party has spent nearly $85,000 on campaign mailers expressly supporting or opposing candidates since mid-September, the party also recently launched a mail campaign that encourages voters to call the Republican candidate in their district and “thank him for fighting for Maine working people and advocating for lower state taxes.” A Republican mailer in August compared the voting records of GOP legislators and their Democratic predecessors, saying, “What a difference one year can make.” By avoiding express advocacy, the party hasn’t had to publicly report spending for those mailings or which legislative districts they targeted. “It just depends on what kind of a message we want to send to which district,” said Maine GOP spokesman David Sorensen. “Sometimes an advertisement that doesn’t expressly say, ‘Vote for so and so,’ is a little more convincing. Other times, we see fit to expressly say, ‘Vote for so and so.’” The Senate race that’s most consistently attracted the parties’ attention so far is in Senate District 32, where Democrats have spent $23,000 on mailers so far in hopes of recapturing a seat they lost in 2010. First-term Republican Sen. Nichi Farnham of Bangor is facing a challenge from Democrat Geoffrey Gratwick in that district. Farnham said the mailers aren’t coming up in her conversations with voters. “I’m doing what I set out to do in my plan,” she said, “which was to go door to door and meet with as many voters as possible. Another district that has captured the attention of both parties is Senate District 20 in Lincoln and Knox counties, where Democrats are trying to defend their special election victory in February. That’s when Sen. Chris Johnson of Somerville won what was a Republican seat. Republicans, whose candidate is Rep. Les Fossel of Alna, are trying to recapture it. Johnson said outside mailers don’t seem to be making a difference at this point in the campaign. “I haven’t heard from anyone saying I’ve received a mailer and it changed my mind,” he said. The parties have targeted more than three dozen House districts in recent mailing campaigns. Reinholt said the Democratic Party is targeting a number of districts where Democrats lost seats in 2010, when Republicans took over control of both the House and Senate. In deciding on races to target, she said, Democrats also consider whether their candidates have built up strong volunteer and supporter networks and whether voters seem to be responding well when the candidates knock on doors. “There’s no denying our top priority is winning back the Legislature,” Reinholt said. Sorensen said Republicans take into account polling, whether their candidates are well known in their communities and a range of other factors in deciding which races to target. “We are incredibly confident with our slate of candidates,” he said. And campaign mail pieces, along with phone calls to voters, are a key part of what the political parties do to support their legislative candidates in key districts. “They’re cost-effective,” Sorensen said. “They’re eye-catching when you get a big, glossy mailer.” And they’re targeted precisely to voters in a particular district, said Reinholt. “When it comes to the size of our House districts, going up on radio and TV does cost a lot of money,” she said. “We have to use our resources really smartly, and you never know how many people you’re connecting with when you go on TV and radio.” In addition to heated competition, said Tardy, the former House Republican leader, legislative mailers are coming earlier this year than they have in the past as an increasing number of people cast their ballots early. But spending on mailers from both sides is likely to pick up in the final month of the campaign, he said. “That’s typically how the final month of the campaign goes,” Tardy said. “The mailboxes become targets.”
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Hemodynamic and morphologic evaluation of sequelae of primary upper extremity deep venous thromboses treated with anticoagulation. This study was performed to describe venous function, residual morphologic abnormalities, and the occurrence of post-thrombotic syndrome in patients with conservatively treated primary upper-extremity deep venous thromboses (UEDVT). This was a retrospective follow-up study of 31 patients with previous primary UEDVT treated with anticoagulation only, identified by a search of medical records. The mean follow-up time was 5 years. The patients were evaluated by interview, clinical examination, computerized strain-gauge plethysmography, and color duplex ultrasound imaging. The grade of post-thrombotic syndrome was rated according to the Villalta score (0 to 3 on each of four subjective and five clinically assessed features). The rate of venous emptying was significantly lower in the arms with DVTs than in the contralateral arms (P < .001). Eleven of the patients (35%) had a remaining outflow obstruction in the affected arm (venous emptying <68 mL/100 mL per min). Eighteen (58%) had a residual thrombus according to color duplex ultrasound scans, with four remaining occluded subclavian veins. None of the patients had deep or superficial venous reflux. There was no statistically significant relationship between plethysmographic and duplex findings. Most (77%) of the patients reported remaining symptoms in the affected arm, and there was a significant side difference in upper arm circumference (P < .001). Approximately one third had developed a moderate grade of post-thrombotic syndrome according to the Villalta score (total, 5 to 9). No significant relation was evident between the post-thrombotic syndrome score and duplex findings. Patients with post-thrombotic syndrome had a lower venous emptying value than those without (69 vs 84 mL/100 mL per min), but this difference was not statistically significant. Patients with conservatively treated previous primary UEDVT had significantly reduced venous outflow capacity and a residual thrombus was common. Swelling of the arm was the most common symptom, and one third had a moderate grade of post-thrombotic syndrome. However, there was no clear relation between hemodynamic and morphologic factors and the development of post-thrombotic syndrome in these 31 patients, examined at a mean of 5 years after an acute DVT episode.
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Salmonella excretion in adult cattle on the Maltese island of Gozo. A cross-sectional study was conducted, between June and November 1993, to determine the prevalence of Salmonella excretion in a representative sample (n = 300) of adult cattle, chosen by strict random sampling of the isolated bovine population in Gozo. Salmonellae were found in 41.3% of the cattle investigated, and seven animals yielded multiple Salmonella serovars. The total number of Salmonella isolates was 131. These included Salmonella Croft (55 isolates), S. Telaviv (29), S. Montevideo (17), S. Kpeme (7), S. Infantis (2) and S. Abadina (1). A seventh serovar (14 isolates) was found to have a novel antigenic structure: the name S. Gozo was proposed, and was accepted by the World Health Organisation Salmonella Reference Centre. All isolates were sensitive to four antibiotics, while 43% of the Salmonella strains were sensitive to nine antibiotics. No resistance was detected to cefuroxime, ciprofloxacin and gentamicin.
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BlueFinity International supplies Microsoft-centric tools which allow MultiValue developers to create applications using the very latest technologies while retaining their valuable and often substantial investment in MultiValue software and knowledge. Today, BlueFinity International has extended its reach to enable applications running on any flavor of MultiValue database to be deployed across any of the wide range of today's interface devices – tablets, handhelds, phones and other mobile devices. "From our personal lives to how we do business, there is no doubt that modern technology has changed the way we do just about everything," explains Pete Loveless, CEO of BlueFinity International. "There is a rapidly growing trend, fuelled by the rapid uptake of smartphone and tablet devices, for IT strategy to be driven by end-user expectation. Ultimately, it's all about being able to deliver solutions that address the evolving needs and expectations of users and customers. Using mv.NET, it is possible to take your tried and trusted MultiValue applications to new heights by creating powerful mobile solutions that address these needs quickly and cost effectively." Many BlueFinity customers have already taken MultiValue on the move and are reaping the benefits today. The largest US distributor of aluminium sheet products is using mv.NET to deliver their MultiValue application on mobile phones to enable real time information access and updates for their sales and management teams while in the field. "Taking our application mobile greatly improves the productivity of our sales force as it enables them to retrieve and input information about their customers while the information is fresh in their minds rather than having to update the database at a later time," says Cliff Ponce, Systems Development Manager at Eastern Metal Supply. "Our general managers are able to access real-time reports and our IT team can diagnose and resolve problems - all from their phones. We were able to maximize on the investment we've already made in our MultiValue application to meet the needs of today's modern business, and mv.NET made the move to mobile easier than we even expected." UK-based applications provider to the office supplies industry, Calidore Computer Systems, has also given their MultiValue application wings and enhanced the sequence of their order delivery process to provide electronic, seamless proof of delivery to their back office MultiValue system on a Windows 7 Phone. "The idea of a proof of delivery application isn't new, but purchasing a new system of this type is extremely expensive," explains Richard Olds, Director at Calidore. "mv.NET allows us to record signatures and delivery information on a Windows 7 phone and automatically update the order history in the back office system with an image of the signature and even enables automatic emailing of the invoice and delivery note to the customer all by simply pressing a button on the phone." .NET developers don't even need MultiValue knowledge to produce applications. "The development cycle was very short – astonishingly short, actually! We were able to use our in house developers who had no knowledge of mv.NET or MultiValue. The application was developed entirely using industry standard technology in Visual Studio 2010," explains Olds. Because BlueFinity provides all of the 'plumbing' and framework to support the application creation process, developers can save valuable time and money as well as reduce the inherent risks of developing their own framework in getting the application implemented and ready to launch. "Using mv.NET's powerful, automatic web service generation capabilities, developers are able to create industry standard web services to populate user interfaces with MultiValue resident data in a fraction of the time normally taken to build this type of infrastructure," explains David Cooper, Lead Developer at BlueFinity. "This, combined with the fact that by using mv.NET you are not tying your solution to a particular MultiValue implementation makes mv.NET an attractive proposition for MultiValue developers needing to deliver modern user interfaces for their existing applications." Loveless concludes: "Over the past few years, the significant rise of mobile device usage and the huge advances in mobile technology have brought about a number of opportunities for businesses to connect with consumers and increase sales. BlueFinity's goal is to allow the MultiValue community to be in the forefront of this exciting opportunity. Enhancements to the product are continuing and some exciting announcements will be made as we approach the third quarter of this year. Watch this space!" BlueFinity International, part of the Mpower1 group of companies, supplies leading-edge software development tools and consultancy services to the MultiValue database and Microsoft developer communities. Its flagship product - mv.NET - is a comprehensive solution for developers wishing to access MultiValue databases from within Microsoft's .NET environment.
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The Drama Of Being A Venture Capitalist Isn’t Really For Me - thankuz http://techcrunch.com/2011/04/26/gideon-yu-drama-venture-capitalist/ ====== phlux What is the TL;DR regarding his reputation, I haven't particularly followed his career... Would it be safe to assume that he tried to overly apply his CFO mentality to tech/eng? I have had way too many CFOs like that in my past...
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172 Cal.App.2d 372 (1959) THE PEOPLE, Respondent, v. JUNIOR GRAYSON, Appellant. Crim. No. 2895. California Court of Appeals. Third Dist. July 27, 1959. Douglas C. Busath, under appointment by the District Court of Appeal, for Appellant. Stanley Mosk, Attorney General, Doris H. Maier and G. A. Strader, Deputy Attorneys General, for Respondent. SCHOTTKY, J. An information was filed charging appellant with six counts of violation of the Health and Safety Code, section 11500. Counts I, II, III, V, and VI charged the appellant with having sold a narcotic, marijuana, on October 10, October 13, October 24, October 9, and November 5, 1957, respectively. Count IV charged the appellant with possession of a narcotic, marijuana, on November 6, 1957. Appellant was found guilty by a jury on all six counts, and this appeal is from the judgment entered on the verdicts. At the trial Hector Reyna, a special investigator for the Bureau of Narcotic Enforcement of California, testified that he had purchased quantities of marijuana cigarettes from appellant on five occasions. The respective purchases were offered in evidence and were properly identified as marijuana. Appellant was arrested on November 5th, after Reyna had purchased five marijuana cigarettes from him. After the appellant *375 had been arrested, a search was made of his room by state narcotic inspector, Major McBee, in company with Vallejo police captain, Dan Horan. The arrest of the appellant occurred about 10 p.m. on November 5th, and the search of his room occurred in the early morning hours of November 6th. The officers went to the Manx Hotel, and after inspecting the register and determining that the appellant, Mr. Grayson, lived in room 12, requested and received permission of the landlady to enter the room and they did so after she opened the door for them. A search of the room resulted in the discovery by Captain Horan of 32 marijuana cigarettes hidden in an overstuffed chair in the middle of the room. Appellant does not argue that the judgment is not supported by sufficient evidence but does contend: (1) That the trial court erred in restricting certain cross-examination; (2) That the trial court erred in permitting one of the witnesses to consult notes during the course of the trial; (3) That the trial court erred in admitting hearsay evidence relating to appellant's occupancy of a room in which marijuana was found; (4) That certain evidence was obtained by illegal search and seizure; and (5) That the trial court erred in excluding certain hotel records. Appellant contends that the trial court unduly restricted counsel in his cross-examination of prosecution witnesses Hector Reyna and Major McBee. It is argued by the appellant that the cross-examination of Reyna was unduly restricted by the trial court in that counsel was not permitted to test the witness' recollection and credibility. [1] Mr. Reyna testified on direct examination that he was employed by the State Bureau of Narcotic Enforcement on September 28, 1957. He came to Vallejo for the purpose of making purchases of narcotics and was given a list of places where he could make a connection. He then testified as to the various purchases of marijuana cigarettes from appellant. On cross- examination Reyna was questioned concerning his employment, and in doing so, counsel attempted to bring out facts relating to the recent discharge of a state narcotics agent, Fred Braumoeller. The appellant contends that the restricting of cross-examination on this point was error. This contention is without merit. Whether Braumoeller had been "fired" by the state neither related to any fact testified to by Reyna on direct examination nor tended to impeach the witness or test his credibility or recollection of the facts concerning which he testified. *376 [2] A witness may not be cross-examined on matters which are irrelevant or outside the scope of direct examination for the purpose of testing the witness' credibility, nor may unrelated matters be brought out for the purpose of showing that the witness on other occasions made contradictory statements. (See People v. McCarthy, 88 Cal.App.2d 883 [200 P.2d 69]; and People v. Sims, 165 Cal.App.2d 108, at pp. 114-115 [331 P.2d 799].) [3] Appellant also contends that he was not permitted to cross- examine the witness Reyna in regard to Reyna's incarceration in the Alameda County jail, arguing that the fact of Reyna's incarceration impeached his testimony to the effect that he and his wife reside in Oakland. However, the record shows the following: "Q. [By appellant's counsel.] Isn't it a fact that you are presently serving time in the Alameda County Jail? A. That's right, sir. Q. Then you are not residing at the address? The Court: Now hold on. By virtue of an Alameda jail sentence for speeding, that is not a change of his residence. He is still a resident of the place of above, Mr. Raftery." We are unable to see how appellant was prejudiced in any way. The question was asked and answered, and there was no prejudicial error in the court's refusal to permit appellant to pursue the matter further. [4a] Appellant also contends that the court unduly restricted the cross-examination of the witness McBee. Appellant's counsel was cross- examining witness McBee, a state narcotic inspector, and attempted to elicit facts relating to the question of whether the witness Reyna's wife was addicted to the use of narcotics. No such issue had been brought out upon the direct examination of this witness and the questions were obviously outside the scope of the direct examination. The appellant asserted that the purpose of the questioning was to show a motive which might induce Mr. Reyna to perjure himself. However, not only was this testimony improperly sought to be elicited from Mr. McBee on cross-examination but, if admissible at all, it should have been brought out by the appellant's own witness. [5] It is, of course, true that evidence is admissible for the purpose of showing that a witness has a motive for testifying falsely. [4b] The alleged motive in the present case was Mr. Reyna's asserted desire to prevent prosecution of his wife for narcotic addiction or otherwise win favorable treatment from police or prosecuting officials. However, the proper method of showing such motive would have been to establish *377 that the witness had been promised a reward, or that an inducement or threat held out or made to him in return for testimony favorable to the prosecution motivated him to distort or falsify his testimony. There was not the slightest attempt by counsel for the appellant to introduce such testimony. He merely attempted to show on cross-examination of Mr. McBee that Mr. Reyna was a user of narcotics (the witness answered that to his knowledge Mr. Reyna was not a user of narcotics), or that Reyna's wife was a narcotic addict. The questions in no way tended to show a motive adverse to the appellant and were properly excluded. [6] There is no merit in appellant's contention that the trial court committed error in allowing witness Reyna to consult certain memoranda during the course of the trial. He refers to the provisions of the Code of Civil Procedure, section 2047, which provides that a witness may be allowed to refresh his memory by reference to notes or writings made by himself or under his direction at the time when the facts related occurred or when the facts were fresh in his memory. During the course of the trial in the present case, it appeared that Mr. Reyna while on the witness stand had with him certain notes which had been typed by his wife from the witness' original notes made at the time that the facts related therein occurred. The appellant assumes in his argument on appeal that after objection by counsel for the appellant the court permitted the witness to use the notes on the stand and that the witness did so. The appellant has pointed to no portion of the record on appeal which would support any such contention, and an examination of the record clearly indicates that the witness did not consult his notes on the stand after the appellant's objection to the use of the notes was sustained. [7] There is some indication from the record that this witness may have refreshed his memory during the recess or prior to coming to court. However, it is clearly established that there is no objection to a witness refreshing his recollection and memory prior to taking the witness stand, and there can be no objection to the use of notes for this purpose so long as the notes are not actually used on the witness stand. (People v. Gallardo, 41 Cal.2d 57 [257 P.2d 29].) [8a] Appellant contends further that the evidence in support of the charge of possession of narcotics is supported solely by incompetent evidence and is therefore insufficient. It is argued that there exists only hearsay evidence to show that *378 the appellant occupied room 12 of the Manx Hotel where the narcotics were found in the chair. The testimony in support of this count consists of the testimony of Officer Horan and Inspector McBee. After the arrest of the appellant, these officers went to the Manx Hotel where they examined the register and discovered that the appellant was registered in room 12; they further ascertained from the landlady that the defendant was the only one living in the room, and with the assistance of the landlady they entered the room and searched and discovered the marijuana cigarettes. The appellant was seen entering the Manx Hotel just before his arrest. However, the record shows that there was no objection by counsel for the appellant to the introduction of any of this evidence relating to Count IV charging possession of narcotics. In fact, counsel for the appellant not only failed to object, but much of the testimony on this point was brought out on cross-examination by appellant's counsel. [9] It is a general principle of law, well established in this state, that material and relevant evidence on an issue, even though hearsay and technically incompetent and inadmissible, which is offered and received without objection will be considered in support of the judgment. (People v. Stepp, 82 Cal.App.2d 49 [185 P.2d 417]; People v. Kelly, 77 Cal.App.2d 23 [174 P.2d 342].) [8b] In the absence of any objection by the appellant, the evidence consisting of the testimony of Inspector McBee and Officer Horan adequately established that the appellant resided in and was the sole occupant of room 12 of the Manx Hotel in which the narcotics were discovered hidden in a chair. The evidence is therefore sufficient to support the judgment on this count. (People v. Vice, 147 Cal.App.2d 269 [305 P.2d 270]; People v. Noland, 61 Cal.App.2d 364 [143 P.2d 86].) [10a] Appellant contends also that the evidence relating to the count of possession was obtained by illegal search and seizure. Appellant argues that even assuming that the room in which the marijuana cigarettes were found was shown to have been occupied by the defendant the evidence of the possession of the narcotics in the room was obtained by an illegal search and seizure. The record shows that the arresting officers after having arrested the appellant went to his room and there conducted the search in question. Even if it could be inferred that there was a possible illegal search and seizure in the present case, it is clearly established that this contention may not be raised for the first time on *379 appeal. The record in the present case shows that there was no objection to the introduction of marijuana cigarettes into evidence and there was no objection to the testimony of the officers who searched the room and found the narcotics. [11] It is now clearly established by numerous decisions that the exclusionary rule of People v. Cahan, 44 Cal.2d 434 [282 P.2d 905, 50 A.L.R.2d 513], is strictly a rule of evidence, and that objections to the introduction of illegally obtained evidence cannot be reviewed on appeal in the absence of a proper objection in the trial court. (See People v. Shannon, 147 Cal.App.2d 300 [305 P.2d 101]; People v. Mann, 148 Cal.App.2d 525 [307 P.2d 48]; People v. Brittain, 149 Cal.App.2d 201 [308 P.2d 38].) [10b] An exception to this rule has been made in cases where the trial occurred prior to the issuance of the Cahan decision. (See People v. Maddox, 46 Cal.2d 301 [294 P.2d 6].) However, the present case was tried long after the decision in the Cahan case, and at the time of trial the Cahan rule was well known throughout the legal profession. If there was any objection which could have been made to the introduction of this evidence on the grounds of illegal search and seizure, that objection should have been made in the trial court; and in the absence of such objection the point must be deemed to have been waived and cannot be raised for the first time on appeal. (People v. Howard, 150 Cal.App.2d 428 [310 P.2d 120]; People v. Davis, 157 Cal.App.2d 33 [320 P.2d 88].) [12a] Appellant's final contention is that the trial court erred in sustaining an objection to the introduction in evidence of a hotel register. The appellant sought to introduce in evidence at the trial a partial or mutilated register of the Hotel Manx. A Mrs. Bell was called as a witness and testified that she was the part-time manager of the hotel in the fall of 1957 and that she was familiar with the hotel register. She was shown a package containing pages which she identified as the hotel register for the periods of September, October, and November, 1957. The pages had been part of a book but had been cut out. The pages had been given to the witness by "her boss." The witness testified that there were two registers, one for "transients" and one for "regulars." These pages were taken from the book for "regulars." An objection was sustained to the introduction of the pages on the ground that the pages were only a partial record and no sufficient foundation had been laid. This witness then *380 returned to the hotel and picked up the rest of the register which she brought to court. The witness testified that these were all of the records that she knew of; that she had "access to these books" and "recognized" them. After further argument by counsel, the court denied the appellant's offer to introduce them in evidence. The appellant states in his opening brief, "It will be admitted that an imperfect foundation was laid for the admission of the records, but the witness testified that they were full and complete records." However, the record very clearly shows that the records were mutilated and that a number of the pages had been removed from the register. The witness when asked whether these were full and complete records replied, "All I know of, yes" and "For all I know about." The trial court refused to permit the introduction of these records upon the grounds that an insufficient foundation had been laid and they were not shown to be true and complete. The records were in fact mutilated, some of the pages having been removed. The Code of Civil Procedure, section 1953f, provides as follows: "A record of an act, condition or event, shall, insofar as relevant, be competent evidence if the custodian or other qualified witness testifies to its identity and the mode of its preparation, and if it was made in the regular course of business, at or near the time of the act, condition or event, and if, in the opinion of the court, the sources of information, method and time of preparation were such as to justify its admission." (Emphasis added.) [13] It has been held that this section gives to the trial court a wide discretion in determining whether or not the mode of preparation of business records, etc., justifies their admission. The section specifically provides that the records are admissible "if in the opinion of the court" the sources of information, methods of preparation, etc., justify their admission. This places a broad discretion in the trial court which will not be disturbed on appeal. (Richmond v. Frederick, 116 Cal.App.2d 541 [253 P.2d 977].) [12b] In the present case the foundation for the admission of these alleged business records was not established. The section above quoted clearly provides that the foundation must include evidence as to the mode of preparation and the fact that the entries were made in the regular course of business at or near the time of the act, condition or event. The only *381 fact established by the appellant in the present case was the identity of the hotel register. Having failed to show the mode of preparation, there was not sufficient foundation for the introduction of the records. (Luthringer v. Moore, 31 Cal.2d 489 [190 P.2d 1].) The records were also properly excluded on the grounds that they were not shown to have been made in the regular course of business. (Pruett v. Burr, 118 Cal.App.2d 188 [257 P.2d 690].) The judgment is affirmed. Van Dyke, P. J., concurred.
{ "pile_set_name": "FreeLaw" }
Background {#Sec1} ========== Rectal cancer (RC) is one of the most common malignancies in the USA, and the incidence of RC in Asian countries is increasing rapidly and has been considered to be similar to that of the Western countries \[[@CR1]\]. Preoperative radiotherapy (Pre-RT) has become part of standard practice offered to improve treatment outcomes in patients with RC because of the oncologic benefit of reduced local recurrence rate \[[@CR2]\]. But till now, there is still lack of effective means for accurate prognostic evaluation on the survival. It is widely thought that lymph node (LN) metastasis indicates worse tumor response grade and poorer survival. According to the guidelines for RC from the National Comprehensive Cancer Network, a minimum of twelve lymph nodes must be retrieved and examined for accurate staging and the number of metastatic LNs was validated as an independent prognostic factors \[[@CR3]\]. While the node-positive patients with RC are heterogeneous and the prognosis of these patients cannot be stratified by the node-stage only \[[@CR3], [@CR4]\]. Therefore, the concept of negative lymph node (NLN) counts has attracted attention recently as a prognostic indicator in various cancers, including breast \[[@CR5]\], cervical \[[@CR6]\], and esophagus \[[@CR7]\]. It has been reported that the number of NLNs was an independent prognostic factor for patients with colon cancer \[[@CR8]\]. However, Pre-RT can yield tumor downstaging, reduce the burden of residual microscopic disease at surgery and reduce the number of LNs retrieved in operation \[[@CR9]\]. With the decreased LNs retrieval, the prognostic value of the LN count might also diminish \[[@CR10]\]. It has been reported that increased number of NLNs is associated with improved survival in pathological IIIB and IIIC RC treated with Pre-RT \[[@CR7]\]. While it is still unclear whether NLN still has prognostic value count on survival of all patients with RC, including stage I and II, who received Pre-RT. The purpose of this study was to assess the association between NLN count and survival of patients with RC of all stages who received Pre-RT. In order to get convincing results in a larger series patients, we used the SEER (Surveillance, Epidemiology and End Results)-registered database to analyze this association, and determine the optimal cutoff value of NLN count. Methods {#Sec2} ======= Study population and data extracted {#Sec3} ----------------------------------- The SEER (Surveillance, Epidemiology, and End Results Program) database and SEER-stat software (SEER∗Stat 8.3.2) were used to identify patients whose pathological diagnosis as RC between 2004 and 2010. Only patients who underwent Pre-RT and surgical treatment with age of diagnosis more than 18 years were included. Histological type were limited to adenocarcinoma (8140/3), carcinoma (8010/3; 8020/3; 8021/3 and 8145/3) and signet ring cell carcinoma (8490/3). Patients were excluded if they had only local excision following Pre-RT, multiple primary malignant neoplasms, incomplete TNM staging, with distant metastasis (M1), no evaluation on LNs, died within 30 days after surgery or information on CSS and survival months unavailable. Year of diagnosis, age, sex, race, grade, histologic type, ypT stage, number of LNs examined, number of positive LNs and CSS were assessed. TNM classification was restaged according to the criteria described in the AJCC Cancer Staging Manual (7th edition, 2010). Statistical analysis {#Sec4} -------------------- The NLNs cutoff points were determined using the X-tile program, which identified the cutoff value with the minimum *P* values from log-rank χ2 statistics for the categorical NLNs in terms of CSS. Baseline characteristics were compared using the X2 test for nominal variables. Survival curves were generated using Kaplan-Meier analyses, and the differences between the curves were analyzed by log-rank test. Cox regression models were built for analysis of risk factors for survival outcomes. Statistical analyses were performed using the statistical software package SPSS for Windows, version 19.0 (SPSS Inc., Chicago, IL). All *P* values were two-sided. *P* \< 0.05 was considered statistically significant. Results {#Sec5} ======= Patient characteristics from SEER database {#Sec6} ------------------------------------------ In SEER database, we selected a total of 6068 patients with RC who received Pre-RT, including 3881 male and 2187 female from 2004 to 2010. The median age of patients was 59 years. There were 4042 patients with stage ypN0, 1352 with stage ypN1 and 674 with stage ypN2. The optimal cutoff value for NLN count calculated by X-tile {#Sec7} ----------------------------------------------------------- To assess the influence of different NLN count on CSS, we analyzed the individual result using different NLN count ranging from 0 to 23. The 5-year CSS was calculated for patients with N (NLNs number) or more nodes and less than N nodes. As shown in Table [1](#Tab1){ref-type="table"}, NLN count in patients with RC who received Pre-RT was a prognosis factor for number ranging from 0 to 23. With the NLN count increased from 0 to 23, the 5-year CSS rate increased from 51.8 to 88.8% (Table [1](#Tab1){ref-type="table"}). Next X-tile plots were constructed and the maximum χ2 log-rank value of 78.060 (the number as 9, Fig. [1](#Fig1){ref-type="fig"}, *P* \< 0.001) was produced, applying 9 as the optimal cutoff value to divide the cohort into high and low risk subsets in terms of CSS. There was a significant improvement in 5-year CSS between two subsets (74.3% v.s. 82.8%, Table [1](#Tab1){ref-type="table"}). As shown in Table [2](#Tab2){ref-type="table"}, the year of diagnosis, sex, age and the average number of LNs dissected were significantly different between patients with NLN ≤ 9 or \>9 (*P* \< 0.05).Table 1Univariate analysis of the influence of different NLN count on CSS in RC patients who received Pre-RTLNsNo.5-year CCSχ2*P* valueLNsNo.5-year CCSχ2*P* value≤07251.8%41.7450.000≤12368576.5%42.7630.000\>0599679.5%\>12238383.3%≤123063.5%50.1000.000≤13402276.9%38.7470.000\>1583879.7%\>13204683.6%≤244468.2%44.1320.000≤14432077.3%33.9390.000\>2562480.0%\>14174883.7%≤372069.0%54.4960.000≤15458577.3%36.4350.000\>3534880.5%\>15148384.8%≤4101570.0%67.3750.000≤16482277.6%33.0370.000\>4505381.0%\>16124685.3%≤5131471.8%68.4320.000≤17501372.8%27.8270.000\>5475481.2%\>17105585.4%≤6162572.5%74.9790.000≤18517778.0%23.5460.000\>6444381.6%\>1889185.5%≤7197473.5%74.3020.000≤19530278.0%25.4480.000\>7409481.9%\>1976686.8%≤8228574.2%70.4050.000≤20542278.2%25.2570.000\>8378382.1%\>2064687.2%≤9261374.3%78.0600.000≤21552877.9%21.1200.000\>9345582.8%\>2154087.5%≤10297375.0%67.2360.000≤22560678.4%21.7300.000\>10309583.1%\>2246288.0%≤11332075.6%57.6630.000≤23567178.5%18.8720.000\>11274883.4%\>2339788.8% Fig. 1X-tile analysis of survival data from the SEER registry. X-tile analysis was performed using patient data, equally divided into training and validation sets, from the SEER registry. In X-tile plots of the training sets (**a**), the plots of matched validation sets are shown in the smaller inset. The optimal cut-point highlighted by the *black circle* (**a**) is shown on a histogram of the entire cohort (**b**), and a Kaplan-Meier plot (**c**). *P* values were determined using the cutoff point defined in the training set and applying it to the validation set. (The optimal cutoff value for NLN count is 9, χ2 = 78.060, *P* \< 0.001) Table 2Comparison of clinical characteristics of patients with NLN ≤ 9 or NLN \> 9CharacteristicTotalNLN ≤ 9NLN \> 9*P* value606826133455Follow upMedian (IQU)58 (42-81) monthsYear of diagnosis0.0002004--20073122155315692008--2010294610601886Sex0.007Male388116252256Female21879881199Age0.000\<60336813652003≥60270012481452Race0.593White492721372790Black511214297Others630262368Grade0.222Grade I/ II509821842914Grade III/ IV970429541Histologic type0.430Adenocarcinoma551723673150Mucinous adenocarcinoma490215275Signet ring cell carcinoma613130ypT stage3861891970.0621957425532243061820248634191792404LNs dissected12.796.9217.230.000 Impact of the NLN count on CSS in RC patients who received Pre-RT {#Sec8} ----------------------------------------------------------------- According to univariate analysis, age (≥ 60), race (black persons), grade (III/IV), histologic type (signet ring cell carcinoma), ypT stage (ypT3 and ypT4) and NLNs (≤ 9) were associated with poor outcomes in patients with RC who received Pre-RT (*P* \< 0.001) (Table [3](#Tab3){ref-type="table"}). In multivariate Cox analysis, age, grade, histologic type, ypT stage and NLN counts were independently prognostic factors (*P* \< 0.001, Table [3](#Tab3){ref-type="table"}). NLN counts (\> 9) exhibited a favorable effect on survival (HR = 1.623, 95% CI 1.457 \~ 1.809, *P* \< 0.001, Table [3](#Tab3){ref-type="table"}).Table 3Univariate and multivariate survival analyses of RC patients who received Pre-RTCharacteristic5-year CCSUnivariate analysisMultivariate analysisχ2 test*P*HR(95%CI)*P*Year of diagnosis2.4120.120NI 2004--200778.4% 2008--201080.2%Sex1.6550.198NI Male29.5% Female78.4%Age21.8050.0000.000 \< 6081.3%Ref ≥ 6076.4%0.777 (0.697 \~ 0.866)0.000Race14.8730.0000.909 White79.5%Ref Black72.7%1.129 (0.937 \~ 1.364)0.202 Others81.8%1.585 (1.246 \~ 2.017)0.000Grade112.3630.0000.000 Grade I/ II81.5%Ref Grade III/ IV66.9%0.596 (0.523 \~ 0.680)0.000Histologic type81.1280.0000.000 Adenocarcinoma80.4%Ref Mucinous adenocarcinoma69.2%0.412 (0.308 \~ 0.635)0.000 Signet ring cell carcinoma32.5%0.601 (0.408 \~ 0.885)0.010ypT stage148.3230.0000.000 188.6%Ref 287.9%0.293 (0.212 \~ 0.405)0.000 377.9%0.303 (0.239 \~ 0.384)0.000 462.6%0.584 (0.494 \~ 0.692)0.000LNs2.2340.135NI ≤ 1278.5% \> 1279.8%NLN78.0600.0000.000 ≤ 974.3%Ref \> 982.8%1.623 (1.457 \~ 1.809)0.000 Impact of the NLN count on CSS in RC patients based on each pathological grade {#Sec9} ------------------------------------------------------------------------------ We then further analyzed of the effects of NLN on survival in each subgroup of stage yp I, yp II and yp III. As shown in Fig. [2](#Fig2){ref-type="fig"}, subgroup analysis showed that NLN was a prognosis factor for patients with RC who received Pre-RT in stage ypI (χ2 = 7.080; *P* = 0.008), ypII (χ2 = 20.806; *P* \< 0.001) and ypIII (χ2 = 33.138; *P* \< 0.001), respectively. Moreover, as shown in Tables [4](#Tab4){ref-type="table"}, [5](#Tab5){ref-type="table"} and [6](#Tab6){ref-type="table"}, the NLN count was also an independently prognostic factor in stage ypII (HR: 1.520, 95%CI: 1.170 \~ 1.975; *P* = 0.002) and ypIII (HR: 1.466, 95%CI: 1.264 \~ 1.700; *P* \< 0.001) after adjustment for potential confounders.Fig. 2Log-rank tests of CSS comparing patients with NLNs (\<9 VS ≥9) for (**a**) stage ypI: *P* = 0.008; (**b**) stage ypII: *P* \< 0.001; and (**c**) stage ypIII: *P* \<0.001 Table 4Univariate and multivariate survival analyses of stage ypI RC patients who received Pre-RTCharacteristic5-year CCSUnivariate analysisMultivariate analysisχ2 test*P*HR(95%CI)*P*Year of diagnosis6.3240.0120.035 2004--200787.9%Ref 2008--201092.2%1.609 (1.029 \~ 2.517)0.037Sex1.2380.266NI Male90.0% Female89.3%Age2.3590.125NI \< 6091.3% ≥ 6088.0%Race6.2220.0450.053 White88.9%Ref Black81.0%3.792 (1.201 \~ 11.968)0.023 Others98.9%4.392 (1.251 \~ 15.415)0.021Grade0.4830.487NI Grade I/ II90.0% Grade III/ IV85.1%Histologic type3.2180.200NI Adenocarcinoma89.8% Mucinous adenocarcinoma89.5% Signet ring cell carcinoma50.0%ypT stage0.0010.972NI 190.5% 289.4%LNs9.4010.0020.284 ≤ 1287.8%Ref \> 1293.4%1.702 (0.949 \~ 3.052)0.074NLN7.0800.0080.600 ≤ 987.6%Ref \> 991.6%1.128 (0.682 \~ 1.866)0.638 Table 5Univariate and multivariate survival analyses of stage ypII RC patients who received Pre-RTCharacteristic5-year CCSUnivariate analysisMultivariate analysisχ2 test*P*HR(95%CI)*P*Year of diagnosis0.2550.614NI 2004--200784.1% 2008--201084.7%Sex1.4140.234NI Male85.1% Female83.0%Age21.4350.0000.000 \< 6087.2%Ref ≥ 6081.1%0.677 (0.566 \~ 0.810)0.000Race1.8120.404NI White84.6% Black81.4% Others84.4%Grade24.5520.0000.000 Grade I/ II85.6%Ref Grade III/ IV76.2%0.599 (0.479 \~ 0.748)0.000Histologic type6.7050.0350.042 Adenocarcinoma85.0%Ref Mucinous adenocarcinoma75.9%0.786 (0.249 \~ 2.481)0.682 Signet ring cell carcinoma71.6%1.103 (0.339 \~ 3.590)0.871ypT stage21.3010.0000.000 385.4%Ref 473.2%0.591 (0.445 \~ 0.767)0.000LNs9.6480.0020.892 ≤ 1282.5%Ref \> 1286.7%0.983 (0.749 \~ 1.289)0.900NLN20.8060.0000.002 ≤ 980.9%Ref \> 986.5%1.520 (1.170 \~ 1.975)0.002 Table 6Univariate and multivariate survival analyses of stage ypIII RC patients who received Pre-RTCharacteristic5-year CCSUnivariate analysisMultivariate analysisχ2 test*P*HR(95%CI)*P*Year of diagnosis0.0380.846NI 2004--200765.6% 2008--201067.0%Sex0.0260.872NI Male65.9% Female66.2%Age17.2450.0000.000 \< 6069.3%Ref ≥ 6060.9%0.747 (0.654 \~ 0.866)0.000Race17.5350.0000.625 White66.8%Ref Black51.6%1.125 (0.880 \~ 1.436)0.347 Others71.3%1.767 (1.290 \~ 2.421)0.000Grade41.7220.0000.000 Grade I/ II69.5%Ref Grade III/ IV53.9%0.670 (0.566 \~ 0.794)0.000Histologic type24.6170.0000.037 Adenocarcinoma67.4%Ref Mucinous adenocarcinoma60.7%0.562 (0.378 \~ 0.836)0.004 Signet ring cell carcinoma41.8%0.588 (0.383 \~ 0.904)0.016ypT stage66.2410.0000.000 173.0%Ref 283.7%0.442 (0.242 \~ 0.810)0.008 365.1%0.276 (0.195 \~ 0.391)0.000 446.8%0.564 (0.451 \~ 0.704)0.000LNs1.9750.160NI ≤ 1264.9% \> 1267.0%NLN33.1380.0000.000 ≤ 960.5%Ref \> 971.4%1.466 (1.264 \~ 1.700)0.000 Discussion {#Sec10} ========== LN metastasis is considered as one of the most significant prognostic factors in RC \[[@CR11]\]. The total number of LNs retrieved is fundamental in most pathological staging systems for RC. Inadequate LN evaluation is associated with worse outcomes in terms of tumor recurrence and patient survival \[[@CR12]\]. Thus, looking for effective means of assessment of LNs on survival can provide more accurate prognostic information. According to the AJCC-7 RC staging system, a 12-node minimum is required for proper tumor stage and associated with a good survival outcome in patients treated with surgery \[[@CR3]\]. Yet, the number of positive LN is often affected by many facts such as neoadjuvant therapy, and the number of LN retrieved and inspected \[[@CR3]\]. Once the range of LN retrieved is not enough, the prediction of survival would be inaccurate. Therefore, the concept of NLN has been developed recently. NLN count has a unique advantage that it is little influenced by the number of LN retrieved \[[@CR13]\]. The more NLN count is, the better the survival would be. Li et al. \[[@CR12]\] reported that the optimal cutoff value of 10 was validated as an independent prognostic factor in stage ypIIIB and ypIIIC RC patients treated with Pre-RT. In this study, we found that the NLN count was an independent prognosis factor for all patients with RC who received Pre-RT. And we identified the optimal cutoff value for NLN count as 9. Obviously, NLN count is a good supplement for LN stage and TNM stage on evaluating the prognosis of patients with RC who received Pre-RT, respectively for patients with stage ypI, ypII and ypIII. Until now, there has been no report confirming the mechanism of NLNs influencing on the prognosis of RC. But it is suggested that lymphatic micrometastasis is a key etiology of recurrence and metastasis after resection of RC \[[@CR14]\]. LN micrometastasis, is common in nodes with the size ranging from 0.2 to 2.0 mm which determined to be negative by HE staining, but positive for cytokeratin (CK) by immunohistochemical staining \[[@CR15]\]. Because it is difficult to find lymphatic micrometastasis during operation, we can retrieve more NLNs to reduce the residual micrometastases, in order to improve the prognosis of RC. The intended purpose of Pre-RT is tumor down-staging by decreasing the primary tumor bulk and reducing the burden of residual associated LN metastases at surgery, thus increasing the potential of margin-negative resections \[[@CR9]\]. It has been reported that Pre-RT may cause radiation-induced lymphocyte destruction and stromal fibrosis resulting in alterations of the morphology of the LNs, making LN detection during operation more difficult \[[@CR9]\]. Some researchers found that a decreased LN count after Pre-RT was related to good survival \[[@CR16], [@CR17]\]. The NLN count is particularly useful in the prediction of survival because it is little influenced by the number of LN retrieved, and has potential to reflect the dissection of lymphatic micrometastasis. In this study, we revealed that NLN count was an independent prognostic factor for patients with RC who received Pre-RT. Subgroup analysis showed that NLN was a prognosis factor for patients with RC who received Pre-RT in stage ypI (χ2 = 7.080; *P* = 0.008), ypII (χ2 = 20.806; *P* \< 0.001) and ypIII (χ2 = 33.138; *P* \< 0.001), respectively. It might provide more accurate prognostic information than the N stage alone in patients with Pre-RT. This study has several limitations. First, the SEER database does not include information of therapeutic options such as detailed information of chemotherapy, targeted therapy, immunotherapy, recurrence and metastasis, which may also impact patients' prognosis. Second, this data lack detailed description of preoperative clinical grading and the information about tumor and LN recession response to treatment, and our analyses could not adjust for these potential confounding factor. Third, different operative approaches, doctors and even pathologist would affect the detective rate of total LN and metastatic LN, but the SEER do not include these information \[[@CR10]\]. Although future clinical research will be required to confirm the role of NLN, our study has its convincing power for it is one of the largest population based study until now. Conclusions {#Sec11} =========== Our results firmly demonstrated that NLN count was an independent prognostic factor for patients with RC who received Pre-RT. It could provide more accurate prognostic information for RC patients with Pre-RT (stage ypI, ypII and ypIII, respectively). LN : Lymph node NLN : Negative lymph node Pre-RT : Preoperative radiotherapy RC : Rectal cancer SEER : Surveillance, Epidemiology, and End Results Program The authors acknowledged the efforts of the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER database. The interpretation and reporting of these data were the sole responsibility of the authors. Funding {#FPar1} ======= The design of the study and collection, analysis, and interpretation of data were supported by National Natural Science Foundation of China to Xinxing Li (Grant No. 81402002). Availability of data and materials {#FPar2} ================================== The cohort data are available to researchers and should be requested under the approval of the SEER Program administration. The other datasets supporting the conclusions of this article are included within the article. Authors' contributions {#FPar3} ====================== ZQH conceived and designed the study, XXL, HLW and XWL performed the analyses, KX, HLW and XWL provided assistance in writing the manuscript and support in interpreting results. All authors discussed the results and implications of the analysis and commented on the manuscript at all stages. All authors read and approved the final manuscript. Competing interests {#FPar4} =================== The authors declare that they have no competing interests. Consent for publication {#FPar5} ======================= Not applicable. Ethics approval and consent to participate {#FPar6} ========================================== Because the patients in the SEER database could not be identified, the analysis and reporting of the data in our study were exempt from review by the Ethics Board of Changzheng Hospital, the Second Military Medical University. The requirement for written informed consent to participate was waived. We were permitted to have Internet access after our signed data-use agreement (<http://seer.cancer.gov/data/sample-dua.html>) was approved by the SEER administration. Publisher's Note {#FPar7} ================ Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
{ "pile_set_name": "PubMed Central" }
Q: How to create HTML element in Qt? Qt has its own wrapper on WebKit (QWebNode, QWebElement, etc). How can I create HTML element using that Qt wrapper (obtain QWebElement of new HTML element)? If it can help, say we have QWebFrame frame. A: The only method I found is to call appendInside, appendOutside, etc methods of existing QWebElement elements with QString html markup as an argument. QWebElement existingElement; existingElement.appendInside( '<div/>' ); QWebElement newElement = existingElement.lastChild();
{ "pile_set_name": "StackExchange" }
Q: how do I get the index from this function this is demo of iOS Charts library (LineChart) and I want to input my data instead of arc4random data. My data is in Array so I have to approach with index but I can't understand the (0..<count).map { (i) -> ChartDataEntry code. func setChartValues(_ count : Int = 24) { let values = (0..<count).map { (i) -> ChartDataEntry in let val = Double(arc4random_uniform(UInt32(count))+3) return ChartDataEntry(x: Double(i), y: val) } let set1 = LineChartDataSet(entries: values , label : "DataSet 1") let data = LineChartData(dataSet: set1) self.lineChartView.data = data } A: It seems you are new to iOS and swift. What you are looking for is an understanding of the functionning of closures in swift, plus the map function which is called an high order function from apple doc ( https://developer.apple.com/documentation/swift/array/3017522-map ) : Returns an array containing the results of mapping the given closure over the sequence’s elements. In other words it maps your array into another array, according to the trailing closure you passed as a parameter. In your specific case here his how to read it : (0..<count) : creates an array of count lengh example : if count = 4 then (0..<count) is [0, 1, 2, 3] As said previously the map function will transform each of your element into another ( therefore keeping the length of the array ). in your case val = Double(arc4random_uniform(UInt32(count))+3) will be equal to a random number calculated with count value, and create a new ChartDataEntry with this random value. to sum it up the whole code is just saying "I will create a count length array of random ChartDataEntry", I guess as a mockup I suggest you to read about closures here : https://medium.com/the-andela-way/closures-in-swift-8aef8abc9474 and high order functions ( such as map(_:) ) here : https://medium.com/@abhimuralidharan/higher-order-functions-in-swift-filter-map-reduce-flatmap-1837646a63e8
{ "pile_set_name": "StackExchange" }
/** ****************************************************************************** * @file stm32f0xx_hal_spi_ex.c * @author MCD Application Team * @brief Extended SPI HAL module driver. * This file provides firmware functions to manage the following * SPI peripheral extended functionalities : * + IO operation functions * ****************************************************************************** * @attention * * <h2><center>&copy; COPYRIGHT(c) 2016 STMicroelectronics</center></h2> * * Redistribution and use in source and binary forms, with or without modification, * are permitted provided that the following conditions are met: * 1. Redistributions of source code must retain the above copyright notice, * this list of conditions and the following disclaimer. * 2. Redistributions in binary form must reproduce the above copyright notice, * this list of conditions and the following disclaimer in the documentation * and/or other materials provided with the distribution. * 3. Neither the name of STMicroelectronics nor the names of its contributors * may be used to endorse or promote products derived from this software * without specific prior written permission. * * THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS" * AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE * IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE * DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT HOLDER OR CONTRIBUTORS BE LIABLE * FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR CONSEQUENTIAL * DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR * SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER * CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, * OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE * OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE. * ****************************************************************************** */ /* Includes ------------------------------------------------------------------*/ #include "stm32f0xx_hal.h" /** @addtogroup STM32F0xx_HAL_Driver * @{ */ /** @defgroup SPIEx SPIEx * @brief SPI Extended HAL module driver * @{ */ #ifdef HAL_SPI_MODULE_ENABLED /* Private typedef -----------------------------------------------------------*/ /* Private defines -----------------------------------------------------------*/ /** @defgroup SPIEx_Private_Constants SPIEx Private Constants * @{ */ #define SPI_FIFO_SIZE 4 /** * @} */ /* Private macros ------------------------------------------------------------*/ /* Private variables ---------------------------------------------------------*/ /* Private function prototypes -----------------------------------------------*/ /* Exported functions ---------------------------------------------------------*/ /** @defgroup SPIEx_Exported_Functions SPIEx Exported Functions * @{ */ /** @defgroup SPIEx_Exported_Functions_Group1 IO operation functions * @brief Data transfers functions * @verbatim ============================================================================== ##### IO operation functions ##### =============================================================================== [..] This subsection provides a set of extended functions to manage the SPI data transfers. (#) Rx data flush function: (++) HAL_SPIEx_FlushRxFifo() @endverbatim * @{ */ /** * @brief Flush the RX fifo. * @param hspi pointer to a SPI_HandleTypeDef structure that contains * the configuration information for the specified SPI module. * @retval HAL status */ HAL_StatusTypeDef HAL_SPIEx_FlushRxFifo(SPI_HandleTypeDef *hspi) { __IO uint32_t tmpreg; uint8_t count = 0U; while ((hspi->Instance->SR & SPI_FLAG_FRLVL) != SPI_FRLVL_EMPTY) { count++; tmpreg = hspi->Instance->DR; UNUSED(tmpreg); /* To avoid GCC warning */ if (count == SPI_FIFO_SIZE) { return HAL_TIMEOUT; } } return HAL_OK; } /** * @} */ /** * @} */ #endif /* HAL_SPI_MODULE_ENABLED */ /** * @} */ /** * @} */ /************************ (C) COPYRIGHT STMicroelectronics *****END OF FILE****/
{ "pile_set_name": "Github" }
Introduction ============ IgG3 is the predominant IgG subclass in responses against T cell--independent type 2 antigens in mice whereas it constitutes a very low fraction of IgG responses to T cell--dependent protein Ags ([@bib1], [@bib2]). A similar situation is seen with human IgG2 which is considered to be the equivalent of murine IgG3 ([@bib3], [@bib4]). These isotypes have been postulated to play an important biological role in the defense against bacterial infections. In support of this, IgG3-deficient mice were shown to be more susceptible to pneumococcal sepsis than wild-type animals ([@bib5]). IgG3 Abs are efficient activators of C, and although they were first believed to act only via the alternative pathway, it was recently shown that monoclonal anti-erythrocyte IgG3 can activate the classical pathway ([@bib6]). Some biological functions of IgG3 are dependent on C activation, such as the protective effect against *Candida albicans* infections and the pathogenicity in hemolytic anemia ([@bib6], [@bib7]). Another possible effector pathway of IgG3 is via Fc-receptors (FcRs).[\*](#fn1){ref-type="fn"} Early studies demonstrated that macrophages could phagocytose IgG3-coated particles and suggested the existence of a specific FcR for IgG3 ([@bib8]). This receptor has been elusive, and for many years IgG3 was not believed to bind to any of the known murine Fc-receptors for IgG (FcγRI, FcγRIIB, or FcγRIII; reference [@bib9]). However, recent data suggest that FcγRI is the IgG3-binding receptor ([@bib10], [@bib11]). Apart from mediating various effector functions, Abs have the ability to feedback regulate the production of themselves (for a review, see reference [@bib12]). Passively administered, or actively produced, specific Ab can enhance or suppress Ab responses to the Ag they bind to. Regulation is potent, frequently resulting in 99% suppression or several 100-fold enhancement, and only responses to determinants within the immune complex are affected. When TNP-specific IgG1, IgG2a, IgG2b, or IgE are administered together with soluble hapten-carriers, e.g. OVA-TNP, BSA-TNP, or KLH-TNP, the anti-carrier responses are enhanced ([@bib13]--[@bib15]). Enhancement by IgG2a and IgG1 takes place in the absence of C activation ([@bib16]) and in Cr2^−/−^ mice lacking CR1 (CD35) and CR2 (CD21; reference [@bib17]), but is severely impaired in FcRγ^−/−^ mice ([@bib14]). These mice lack the common signaling γ-chain used by both FcγRI and FcγRIII and do not express FcγRIII ([@bib18]), although 1/5 of FcγRI was recently shown to remain ([@bib11]). The data therefore suggest an important role for FcγRs in IgG1- and IgG2a-mediated enhancement. IgE-mediated enhancement is exclusively dependent on the low affinity receptor for IgE, CD23 ([@bib15], [@bib19], [@bib20]). Also, IgM can enhance Ab responses and this effect is dependent on C activation. Mutant monoclonal IgM that has lost its ability to activate C cannot enhance, normal IgM cannot enhance in C-depleted mice or in Cr2^−/−^ mice lacking CD35 and CD35 ([@bib17], [@bib21]), and monomeric IgM, which cannot activate C, does not enhance ([@bib22]). Murine CD21 and CD35 are alternatively spliced from the same Cr2 gene and knockout mice therefore lack both receptors ([@bib23], [@bib24]). CD21 associates with the signaling molecule CD19 in the B cell membrane and cocrosslinking of the B cell receptor (BCR) and CD21/CD19 lowers the threshold for B cell activation ([@bib25]). Cr2^−/−^ mice have poor Ab responses to suboptimal doses of various antigens (for a review, see references [@bib23] and [@bib24]) and it was recently shown that IgG3 was the most severely affected isotype ([@bib26]). These mice were more susceptible to *Streptococcus pneumoniae* infection than wild-type controls ([@bib26]), a finding agreeing well with a role for IgG3 ([@bib5]) and C3 ([@bib27]) in defense against bacterial infections. Whether IgG3, in addition to the isotypes discussed above, can act to enhance humoral responses has not been examined. We here report that TNP-specific IgG3 mAbs, administered in complex with BSA-TNP or OVA-TNP, dramatically increase the carrier-specific responses, sometimes \>1,000-fold. IgG3 enhances Ab responses equally well in FcRγ^−/−^ and FcγRIIB^−/−^ as in wild-type control mice. In contrast, the capacity of IgG3 to enhance Ab production was markedly reduced in C3-depleted as well as in Cr2^−/−^ mice, suggesting that IgG3, in analogy with IgM, enhances the Ab response via the C system. Materials and Methods ===================== Antigens. --------- BSA (fraction V, A-3059), OVA (grade V, A-5553), and TNP (picrylsulfonic acid/hydrate) were from Sigma-Aldrich and KLH from Calbiochem. TNP was conjugated to BSA or OVA as described ([@bib28]). The number of TNP residues/Ag molecule was 12 for BSA and 3 for OVA determined according to ([@bib29]). SRBC from the National Veterinary Institute (Uppsala, Sweden), were conjugated to TNP (SRBC-TNP) as described ([@bib30]). Antibodies. ----------- 5-mo-old BALB/c mice (Bommice) were immunized in the tail vein with 4 × 10^8^ SRBC-TNP in 0.1 ml PBS. 3 d before the fusion, mice were boosted intravenously with 4 × 10^8^ SRBC-TNP and 10 μg LPS (Sigma-Aldrich) intraperitoneally. Splenocytes were mixed with the fusion partner Sp 2/0 in a ratio of 5:1 in PBS containing 50% polyethylene glycol 4000 (Merck), at 37°C for 1 min. The fusion mixture was slowly diluted with serum-free DMEM, spun down, and incubated for 15 min at 37°C. The cells were then washed and diluted in DMEM containing 10% heat-inactivated FCS, seeded out in 96-well microtiter plates (Nunc), and cultured overnight at 37°C together with 3 × 10^6^ rat thymocytes per ml. Next day, HAT (Hypoxanthine-Aminopterin-Thymidine) medium (Sigma-Aldrich) was added and the cells were cultured in HAT until growing clones were established. Hybridomas were screened for production of IgG3 anti-TNP by ELISA. Positive hybridomas were expanded and cloned by limiting dilution and clones IM-F10 and IM-H11 were selected for further studies. IgG3 anti-TNP (IM-F10 and IM-H11), IgG2a anti-TNP (C4007B4, 7B4; reference [@bib13]), and IgE anti-TNP (IgEL-A5, mouse IgE/κ; reference [@bib31]) were cultured in DMEM (4.5 g/liter glucose) supplemented with 50 IU/ml penicillin, 50 μg/ml streptomycin, 2 mM [l]{.smallcaps}-glutamin, 10 mM HEPES, 0.05 mM 2-mercaptoethanol, and 5% heat-inactivated FCS. IgG mAbs were purified on a protein A Sepharose column (Amersham Biosciences) and IgE on a Sepharose column coupled with monoclonal rat anti--mouse κ 187.1.10 as described ([@bib17]). Abs were concentrated by Microsep^®^ 10K concentrator (Pall Filtration Corp.) and the storage buffer was changed to PBS using a PD10 column (Amersham Biosciences). Protein concentrations were determined by absorbance at 280 nm, assuming that an absorbance of 1.5 equals 1 mg/ml of Ab. The subclasses of each IgG preparation were confirmed by subclass-specific ELISA. mAbs were sterile filtered and IgG2a and IgE stored at --20°C whereas IgG3 was used immediately or stored in liquid nitrogen. Mice. ----- BALB/c, CBA/J, and DBA/1 were from Bommice. H-2^b^ mice have an I-A^b^-linked low responsiveness to IgE/BSA-TNP and IgG/BSA-TNP complexes ([@bib28], [@bib32]) and the knockout mice used in the present study were backcrossed to responder strains. FcRγ^−/−^ mice ([@bib18]) were backcrossed/intercrossed to DBA/1 (H-2^q^) for five generations and offspring from homozygous mutant FcRγ^−/−^/ H-2^q^ and wild-type FcRγ^+/+^/H-2^q^ animals were used in experiments. FcγRIIB^−/−^ mice ([@bib33]) were backcrossed to CBA/J mice (H-2^k^). The fifth generation was intercrossed and offspring from homozygous mutant FcγRIIB^−/−^/H-2^k^ and wild-type FcγRIIB^+/+^/H-2^k^ mice were used in experiments. Cr2^−/−^ mice ([@bib34]), first backcrossed to H-2^k^ mice ([@bib17]), were further backcrossed to DBA/1. Mice from the second generation were intercrossed and offspring from homozygous mutant Cr2^−/−^/H-2^q^ and wild-type Cr2^+/+^/H-2^q^ animals, identified by PCR analysis (described below), were used in experiments. Mice were bred and maintained at the Department of Genetics and Pathology, the Department of Animal Development and Genetics or at the Biomedical Center, Uppsala University. PCR Reactions. -------------- The FcRγ genotype was analyzed according to ([@bib18]), FcγRIIB as described ([@bib35]), and H-2^k^, H-2^b^, and the Cr2 genotype according to ([@bib17]). H-2^q^ was analyzed in a PCR reaction using two primers: αK1:2 (5′ TAT CAG TCT CCT GGA GAC ATT G 3′) and q2 (5′ GTC AAA GCT TGT CAA TTG GC 3′) resulting in a 128 bp band. Gene amplification was done in 20 μl 10 mM Tris-HCl, pH 8.3, 50 mM KCl, 5 mM MgCl~2~, 0.2 mM dNTPs, 0.22 μM of primers, and 2.5 U AmpliTaq DNA polymerase (PerkinElmer) for 35 cycles (30 s, 94°C; 40 s, 54°C; 50 s, 72°C). Immunizations. -------------- Mice were immunized in the tail vein with Ag alone or Ab/Ag complexes in 0.2 ml PBS. Complexes were formed by incubating TNP-conjugated Ag with TNP-specific mAb for 1 h at 37°C, immediately before the immunization. Non-crossreacting Ag (unconjugated OVA, BSA, or KLH) was included in the Ag mixture as a specificity control. Cobra Venom Factor Treatment. ----------------------------- Mice were injected intraperitoneally with four doses of 0.1 ml of 100 U/ml cobra venom factor (CVF) from *Naja haje* (Cordis Laboratories Inc.) during 24 h. Control groups received PBS in the same regimen. All mice were bled individually from the tail 7 d before the first and 2 h after the last CVF injection. C3 levels in sera were assayed by radial immunodiffusion using a polyclonal goat anti-mouse C3 antiserum (Cooper Biomedical, Inc.). Titers are expressed as the reciprocal of the highest dilution giving a precipitation line (e. g. dilution 1:27 = 27). ELISA. ------ Blood was collected from tail veins and sera were tested using IgG anti-BSA-, IgG anti-KLH, or IgG anti-OVA- specific ELISAs ([@bib36]). Statistical differences were determined by Student\'s *t* test. P values are presented as: not significant, NS; P \< 0.05, \*; P \< 0.01, \*\*; P \< 0.001, \*\*\*. Stimulation indices (SI) were calculated as the geometrical mean of the experimental group divided by the geometrical mean of the control group. Hemolysis. ---------- Hemolytic titers are defined as the highest antibody dilution able to lyse a 0.25% suspension of SRBC-TNP~5~ (prepared as described \[[@bib30]\] but with a fivefold lower concentration of picryl sulfonic acid) in the presence of a 1:160 dilution of guinea pig serum in veronal-buffered saline (VBS). Alternative pathway activation was assayed in VBS with Mg-EGTA ([@bib37]). Results ======= Monoclonal TNP-specific IgG3 Enhances Ab Responses to BSA-TNP and OVA-TNP. -------------------------------------------------------------------------- To assess the ability of IgG3 to augment Ab production, mAbs IM-F10 and IM-H11 were administered to CBA/J mice together with BSA-TNP and OVA. Both mAbs were able to enhance the IgG anti-BSA responses (51- and 13-fold respectively) compared with control groups immunized with Ag alone ([Table I](#tbl1){ref-type="table"} , experiments 1 and 2). The response to OVA, included as a specificity control, was not affected by IgG3. Ab responses to BSA in two other strains of mice, BALB/c and DBA/1, were also efficiently enhanced by IgG3 (1344- and 316-fold, respectively; [Table I](#tbl1){ref-type="table"}, experiments 3 and 4). IM-F10 administered to BALB/c mice together with another Ag, OVA-TNP, induced an 81-fold enhancement of the OVA-specific response (unpublished data). Thus, two out of two TNP-specific IgG3 mAbs were able to specifically enhance Ab responses to BSA-TNP or OVA-TNP in three different mouse strains. ###### Enhancement of Ab Responses by Monoclonal IgG3 Ab ---------------------------------------------------------------------------------------------------- IgG anti-BSA IgG anti-OVA --- -------- --------------------- -------------- -------------- --------- -------------- ----- ---- 1 CBA/J BSA-TNP + OVA 2.25 ± 0.35\ 1 c 1.64 ± 0.08\ 1 c (178) (44) BSA-TNP + OVA +\ 3.96 ± 0.26\ 51 \<0.001 1.54 ± 0.11\ 0.8 NS 50 μg IgG3 (IM-F10) (9,076) (35) 2 CBA/J BSA-TNP + OVA 2.20 ± 0.15\ 1 c 2.92 ± 0.19\ 1 c (160) (830) BSA-TNP + OVA +\ 3.30 ± 0.52\ 13 \<0.005 2.81 ± 0.11\ 0.8 NS 50 μg IgG3 (IM-H11) (2,010) (650) 3 BALB/c BSA-TNP + OVA 2.46 ± 0.40\ 1 c 1.98 ± 0.14\ 1 c (290) (97) BSA-TNP + OVA +\ 5.59 ± 0.15\ 1,344 \<0.001 1.74 ± 0.21\ 0.6 NS 50 μg IgG3 (IM-F10) (389,814) (54) 4 DBA/1 BSA-TNP + OVA 2.41 ± 0.05\ 1 c 2.21 ± 0.12\ 1 c (259) (162) BSA-TNP + OVA +\ 4.91 ± 0.43\ 316 \<0.001 2.38 ± 0.07\ 1.5 NS 50 μg IgG3 (IM-F10) (81,835) (240) ---------------------------------------------------------------------------------------------------- Groups of five mice were immunized intravenously with 20 μg BSA-TNP + 20 μg OVA, alone or together with 50 μg TNP-specific mAb IgG3, IM-F10 or IM-H11. 14 d after immunization, mice were bled and sera tested in ELISA. Mean of log~10~ ng/ml for IgG anti-BSA or IgG anti-OVA. Figures within parentheses represent geometrical mean (anti-log). SI, stimulation index, geometrical mean of the experimental group divided by the geometrical mean of the control group. P value vs. control value (c) as determined by Student\'s *t* test; NS, not significant (P \> 0.05). Impaired Ab Responses to IgG3/Ag Complexes in C3-depleted and Cr2^−/−^ Mice. ---------------------------------------------------------------------------- The hemolytic titer of purified IgG3 (1.8 mg/ml) in the presence of Ca^2+^ and Mg^2+^ (both required for C activation via the classical pathway) was 1:256 whereas the titer in the absence of Ca^2+^ (allowing only alternative pathway activation) was reduced to \<1:4. This established that IM-F10 is an efficient activator of the classical pathway, confirming previous data ([@bib6]). We next examined whether IgG3-mediated enhancement was C dependent. Mice where the MHC-II I-A region is of the b haplotype are low-responders to IgE/Ag ([@bib28]), IgG2a/Ag ([@bib32]), and IgG3/Ag (unpublished data). Available C3 and C4-deficient mice are on C57BL/6 and/or 129/Sv (H-2^b^) backgrounds. Since the C4 locus is located within the MHC region, backcrossing to a responder MHC is impossible. The C3 locus is located outside, but close to, the MHC region, and backcrossing to a responder MHC is feasible, albeit complicated. An alternative approach is to deplete mice of C3 using CVF which acts by replacing C3b in the formation of alternative pathway C3 convertase resulting in CVFBb instead of C3bBb complexes. Whereas C3bBb is relatively labile, CVFBb has a half-life of several hours, resulting in transient C3-depletion (production is not affected; reference [@bib38]). Normal CBA/J mice were treated with CVF or sham-treated with PBS. C3 levels in CVF-treated animals were \<5% of the titers in sham-treated mice (C3 titers ± SEM: 2.3 ± 0.25 vs. 49 ± 9.5, respectively). Both groups were immunized with BSA-TNP alone or in complex with 50 μg IgG3 (IM-F10) and tested for BSA-specific IgG. C3-depletion resulted in a significant reduction of responses to IgG3/BSA-TNP complexes ([Fig. 1, A and B](#fig1){ref-type="fig"}) . In contrast, C3-depletion had no significant effect on responses to IgE/BSA-TNP, included as a control ([Fig. 1, C and D](#fig1){ref-type="fig"}). IgE-mediated enhancement is exclusively dependent on the low affinity receptor for IgE, CD23 ([@bib15], [@bib19], [@bib20]) and therefore operates independently of C. Although IgG3-mediated enhancement was significantly impaired in CVF-treated mice, it was not completely absent ([Fig. 1](#fig1){ref-type="fig"} B). One reason for this could be the residual levels of C3. ![IgG3-, but not IgE-, mediated enhancement is impaired in CVF-treated mice. Groups of five FcRγ^+/+^ mice, treated with CVF or sham-treated with PBS, were immunized intravenously with 20 μg BSA-TNP and 20 μg OVA alone or in combination with 50 μg TNP-specific IgG3 (A and B) or IgE (C and D). On the indicated days, mice were bled and the IgG anti-BSA and anti-OVA titers were measured by ELISA. OVA-specific responses were not enhanced by IgG3 or IgE (unpublished data). Asterisks indicate the statistical differences between experimental and control groups within the same strain; asterisks within parentheses indicate the statistical differences between corresponding not-C3-depleted and C3-depleted groups. \*, P \< 0.05; \*\*, P \< 0.01; \*\*\*, P \< 0.001; NS, not significant.](20022232f1){#fig1} Cr2^−/−^ mice respond normally to complexes consisting of IgE/Ag and IgG2a/Ag whereas responses to IgM/Ag are very low ([@bib17]). To further test the C dependence of IgG3-mediated enhancement, Cr2^−/−^ and wild-type mice were immunized with OVA-TNP alone or in complex with 50 μg IM-F10 ([Fig. 2](#fig2){ref-type="fig"}) . IgG3-mediated enhancement was severely impaired in Cr2^−/−^ animals at all times tested. To verify that the impaired responses to IgG3/OVA-TNP were not just an effect of a general low-responsiveness, Cr2^−/−^ mice were immunized also with IgG2a/Ag ([Fig. 3](#fig3){ref-type="fig"}) . Whereas IgG3-mediated enhancement decreased markedly (SI = 16 in wild-type mice and 5.6 in Cr2^−/−^ mice), IgG2a-mediated enhancement was stronger in Cr2^−/−^ mice (SI = 17 in wild-type mice and 32 in Cr2^−/−^), thus confirming earlier studies ([@bib17]). The results show that IgG3, but not IgG2a, loses most of its enhancing capacity in mice lacking CD21/CD35. Unlike another Cr2^−/−^ line, which expresses a hypomorphic variant of CD21/CD35 ([@bib39]), the Cr2^−/−^ line used here completely lacks expression of CD21/CD31 ([@bib40]). Therefore, the residual enhancement seen in Cr2^−/−^ mice ([Fig. 2](#fig2){ref-type="fig"} B) cannot result from enhancement via a hypomorphic receptor. ![IgG3-mediated enhancement is impaired in Cr2^−/−^ mice. Groups of five Cr2^+/+^ (A) and Cr2^−/−^ (B) mice were immunized intravenously with 20 μg OVA-TNP and 20 μg KLH alone or in combination with 50 μg TNP-specific IgG3. On the indicated days, mice were bled and the IgG anti-OVA and anti-KLH titers were measured by ELISA. KLH-specific responses were not enhanced by IgG3 (unpublished data). Asterisks indicate the statistical differences between experimental and control groups within the same strain; asterisks within parentheses indicate the statistical differences between the corresponding Cr2^+/+^ and Cr2^−/−^ groups. \*, P \< 0.05; \*\*, P \< 0.01; \*\*\*, P \< 0.001; NS, not significant.](20022232f2){#fig2} ![IgG2a-mediated enhancement is normal in Cr2^−/−^ mice. Groups of five Cr2^+/+^ (A) and Cr2^−/−^ (B) mice were immunized intravenously with 20 μg OVA-TNP and 20 μg KLH alone or in combination with 50 μg TNP-specific IgG3 or IgG2a. Mice were bled 14 d after immunization and the IgG anti-OVA and anti-KLH titers were measured by ELISA. KLH-specific responses were not enhanced by IgG3. Asterisks indicate the statistical differences between experimental and control groups. \*\*\*, P \< 0.001.](20022232f3){#fig3} Normal Ab Responses to IgG3/Ag Complexes in FcRγ^−/−^ Mice. ----------------------------------------------------------- Since a small enhancement by IgG3 could be detected both in C3-depleted and Cr2^−/−^ mice ([Figs. 1](#fig1){ref-type="fig"}--[3](#fig3){ref-type="fig"}), we wanted to test whether FcγRs may also be involved. FcRγ^+/+^ and FcRγ^−/−^ mice were immunized with OVA-TNP alone or in complex with IgG3 (IM-10). IgG3 enhanced the OVA-specific Ab response equally efficiently in both strains ([Fig. 4](#fig4){ref-type="fig"}) . These experiments were repeated using BSA-TNP as the Ag and yielded similar results (unpublished data). Thus, IgG3 enhances well in mice lacking expression of FcγRIII and with reduced expression of FcγRI. ![IgG3-mediated enhancement is normal in FcRγ^−/−^ mice. Groups of four FcRγ^+/+^ and FcRγ^−/−^ mice were immunized intravenously with 20 μg OVA-TNP and 20 μg KLH alone or in combination with 50 μg TNP-specific IgG3. On the indicated days mice were bled and the IgG anti-OVA and anti-KLH titers were measured by ELISA. Anti-KLH responses were not enhanced by IgG3 (unpublished data). Asterisks indicate the statistical differences between experimental and control groups within the same strain; asterisks within parentheses indicate the statistical differences between the corresponding FcRγ^+/+^ and FcRγ^−/−^ groups. \* P \< 0.05; \*\*, P \< 0.01; \*\*\*, P \< 0.001; NS, not significant.](20022232f4){#fig4} Normal Ab Responses to IgG3/Ag Complexes in FcγRIIB^−/−^ Mice. -------------------------------------------------------------- Enhancement by TNP-specific IgG1, IgG2a, and IgG2b mAbs administered with BSA-TNP increases dramatically in FcγRIIB^−/−^ mice compared with wild-type controls ([@bib14]). IgG3 is the only IgG subclass reported not to bind to FcγRIIB and it was of interest to test whether IgG3-mediated enhancement was indeed independent on this receptor. Wild-type and FcγRIIB^−/−^ mice were immunized with BSA-TNP alone or in complex with 50 μg IgG3 (IM-F10) and their sera tested for BSA-specific IgG. The Ab responses were enhanced both in FcγRII^+/+^ (11--16-fold of controls) and FcγRIIB^−/−^ mice (16--25-fold of controls; [Fig. 5](#fig5){ref-type="fig"}) . Although IgG3 induced a twofold higher Ab response in FcγRIIB^−/−^ compared with wild-type mice, this difference was not significant and was far less pronounced than the 20--100-fold increased enhancement previously reported with IgG1-, IgG2a-, and IgG2b-complexes ([@bib14]). The response to uncomplexed Ag is similar in FcγRIIB^−/−^ and wild-type mice ([Fig. 5](#fig5){ref-type="fig"}). In light of the fact that immunization with proteins without adjuvant induces very little production of IgG, which is a prerequisite for ligation of FcγRIIB and initiation of its negative regulation, this is not surprising. Thus, IgG3-mediated enhancement takes place in the absence of FcγRIIB and this receptor does not exert a significant inhibitory influence on responses to IgG3-complexed Ags. ![IgG3-mediated enhancement is normal in FcγRIIB^−/−^ mice. Groups of five FcγRIIB^+/+^ and FcγRIIB^−/−^ mice were immunized intravenously with 20 μg BSA-TNP and 20 μg OVA alone or in combination with 50 μg TNP-specific IgG3. On the indicated days mice were bled and the IgG anti-BSA and anti-OVA titers were measured by ELISA. OVA-specific responses were not enhanced (unpublished data). Asterisks indicate the statistical differences between experimental and control groups within the same strain; asterisks within parentheses indicate the statistical differences between the corresponding FcγRIIB^+/+^ and FcγRIIB^−/−^ groups. \*, P \< 0.05; \*\*, P \< 0.01; \*\*\*, P \< 0.001; NS, not significant.](20022232f5){#fig5} Discussion ========== Here we provide the first evidence that IgG3 can positively feedback-regulate Ab production. The augmentation is impressive, frequently yielding several-hundred-fold increases in Ab titers, and is severely impaired in mice lacking CD21/CD35 or in mice with reduced C3 levels. It is well known that C plays an important role for primary as well as secondary Ab responses, and animals lacking C1q, C2, C4, C3, as well as CD21/CD35 have severely impaired Ab responses (for reviews, see references [@bib23] and [@bib24]). In contrast, factor B--deficient mice have normal Ab responses ([@bib41]; unpublished data) suggesting that the alternative pathway is not required for up-regulation of Ab responses and that classical pathway activation (via immune complexes) plays a major role. One explanation for the role of C in Ab responses is that immune complexes, containing C factors, cocrosslink BCR and the CD21/CD19-receptor complex on the B cell surface and thereby lowers the threshold for B cell activation, as shown to take place in vitro ([@bib25]). A mutually not exclusive hypothesis is that Ab/Ag/C complexes are captured by follicular dendritic cells in the spleen and lymph nodes, increasing the effective concentration of Ag ([@bib22], [@bib42], [@bib43]). Our present data suggest that not only IgM ([@bib17], [@bib21], [@bib22]), but also IgG3, uses the C system to initiate feedback "help" for early Ab production. Since classical pathway C activation is important for normal primary Ab responses in animals immunized with Ag alone, an interesting question is how specific Abs, able to recognize Ag and form immune complexes, can be available in naive mice. Mice lacking secretory IgM have impaired primary Ab responses to noncomplexed Ags ([@bib44]--[@bib46]) and a normal response could be reconstituted by transfer of IgM from naive mice. These animals may have several abnormalities in their immune system, secondary to the lack of secretory IgM, and were also reported to have developmental defects in their B cell compartment ([@bib45], [@bib47]). The underlying reason for the impaired IgG responses observed ([@bib44]--[@bib46]) is not known. However, one intriguing explanation would be that "natural" IgM, present without prior (deliberate) immunizations, initiates positive feedback of early responses. Should the enhancing effect of natural IgM be caused by its ability to activate C, which has not been formally proven, it is possible that recognition of Ag by natural IgM is the first step in the C-dependent chain of events leading to efficient early Ab responses to suboptimal doses of Ag. This would explain how classical C activation can play a role already for primary Ab responses. Our present data raises the question whether "natural" IgG3 has a similar role as IgM in enhancing early Ab responses. IgM has only been reported to enhance responses to large Ags such as erythrocytes ([@bib21], [@bib48]), malaria parasites ([@bib49]), and KLH ([@bib22]), whereas responses to small Ags, e.g. BSA-TNP, have not been reported to be enhanced (unpublished data). An explanation for this would be that IgM must bind to an Ag large enough to permit binding of several of its arms in order to achieve the conformation change necessary to bind C1q. IgG3, bound to the surface of e g group A streptococci, is able to facilitate the binding of other IgG3 molecules to the same Ag ([@bib50], [@bib51]). This so called cooperative binding is probably mediated by Fc--Fc interactions and increases the functional affinity of IgG3. The interaction between IgG3 molecules is also evidenced by their tendency to self-aggregate ([@bib52]) and to act as cryoglobulins, i.e. to precipitate in the cold ([@bib53]). Cooperative binding of IgG3 would increase the chances that two or more IgG3 molecules end up close together (and thereby can bind C1q) also on Ags which are too small for IgM to bind with all five arms. This may explain why IgG3, but not IgM, can utilize C to enhance responses to Ags like BSA and OVA. The probability that two IgG2a or IgG2b molecules, subclasses which do not show cooperative binding, bind to the same Ag close enough to be able to fix C1q is smaller and could be the reason that these subclasses preferentially utilize FcγRs for feedback enhancement. Unlike enhancement mediated by IgG1 and IgG2a, IgG3-mediated enhancement was unperturbed in FcRγ^−/−^ mice. Although FcγRI in these animals has lost its signaling function, 20% of the receptor is still expressed ([@bib11]). As FcγRI was also reported to bind IgG3 ([@bib10], [@bib11]), we cannot at this point exclude that FcγRI, or another yet unidentified IgG3-binding receptor, acts redundantly to C in IgG3-mediated enhancement. This would explain the small residual enhancement seen in C-depleted and Cr2^−/−^ mice. Direct experiments to prove this point will have to await the availability of FcγRI^−/−^ mice on a responder background, as H-2^b^ mice, commonly used to produce knockout mice, are nonresponders to soluble IgE- and IgG-immune complexes ([@bib28], [@bib32]). Mice lacking FcγRIIB have augmented humoral, anaphylactic, and inflammatory immune responses (for a review, see reference [@bib54]). This receptor contains a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM), which upon cocrosslinking to receptors containing immunoreceptor tyrosine-based activation motifs (ITAMs), such as the BCR, FcγRI, FcγRIII, and FcɛRI, inhibits activation of the ITAM receptor. Ab production after immunization with IgG1/Ag, IgG2a/Ag, or IgG2b/Ag complexes is considerably higher in FcγRIIB^−/−^ mice than in wild-type controls, implying that FcγRIIB negatively regulates the response to Ag complexed to these isotypes ([@bib14]). IgG3 does not bind FcγRIIB and we here show that enhancement by IgG3 is similar in FcγRIIB^−/−^ and wild-type mice. Therefore, IgG3/Ag complexes have the for IgG isotypes unique possibility to enhance Ab responses without inducing simultaneous negative feedback via cocrosslinking of BCR and FcγRIIB. This feature may be useful to quickly generate a potent primary Ab response to e g bacterial Ags. IgG3 is an isotype frequently involved in autoimmunity ([@bib55]--[@bib58]). In addition to its ability to initiate inflammation via C-activation, the ability of IgG3 to enhance autoantibody production without negative feedback via FcγRIIB may play a role in its pathogenicity. We thank Ms. I. Brogren and Ms. T. Wahlström for skillful technical assistance, Dr. M. Wabl for IgE, and Dr. P. Coulie for IgG2a hybridomas, Dr. H. Molina for Cr2^−/−^, Dr. J.V. Ravetch for FcRγ^−/−^ and FcγRIIB^−/−^, and Dr. S. Kleinau for FcRγ^+/+^ and FcRγ^−/−^ (H2^q^) founder animals. This work was supported by Agnes and Mac Rudberg\'s Foundation; Ellen, Walter and Lennart Hesselman\'s Foundation; Hans von Kantzow\'s Foundation; King Gustaf V:s 80 Years Foundation; Lilly and Ragnar Åkerhams\'s Foundation; The Swedish Foundation for Health Care Science and Allergy Research; The Swedish Medical Research Council; The Swedish Association against Rheumatism; and Ollie and Elof Ericsson\'s Foundation. *Abbreviations used in this paper:* BCR, B cell receptor; CVF, cobra venom factor; FcR, Fc-receptor. [^1]: Address correspondence to Birgitta Heyman, Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden. Phone: 46-18-6113868; Fax: 46-18-55-89-31; E-mail: <[email protected]>
{ "pile_set_name": "PubMed Central" }
Kynan stop being an idiot. You're accusing random people of hacking just because they got a random good score, or their playcount is lower than yours. "Oh there isn't any proof that he is legit, so that's proof that he cheats!" and gayz' top ranks are STREAM MAPS over anything else, so makes sense My accusations or not random AT ALL, and dude, stream maps or not, the guy doesn't even have 30k PC, with that much playcount, you shouldn't even be able to FC 5 star maps, you should realize that before calling me an idiot.
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"A MAN LOSES BOTH LIMBS AND GETS ROBOTIC ONES" "THAT HE CAN POWER WITH HIS MIND." "A GAGGLE OF BABY GEESE ACCEPTS A ZOOLOGIST AS THEIR MOTHER." "AND LEWICKI, HAVING A HARD TIME FINDING ROMANCE," "TURNS TO A VIRTUAL SEX SIMULATOR" "CREATED BY AN ADULT-TOY COMPANY IN JAPAN." "[ LAUGHTER ]" "PROSTHETIC LIMBS, FILIAL IMPRINTING," "JAPANESE SEX ROBOTS." "WHAT DO THEY ALL HAVE IN COMMON?" "THEY'RE ALL REPLACEMENTS." "FROM LIMBS MADE OF STEEL AND WIRES" "TO MOTHERS THAT AREN'T EVEN OF THE SAME SPECIES" "TO HIGHLY EVOLVED SELF-PLEASURE DEVICES " "AS FAR AS THE BRAIN IS CONCERNED, IF IT GETS THE JOB DONE," "DOES IT REALLY MATTER IF IT AIN'T THE REAL THING?" "I ALWAYS KNEW YOU WERE A PERFECT 10," "BUT WHO KNEW YOU WERE A 780?" "EXCUSE ME?" "YOUR CREDIT SCORE." "OKAY, I KNOW MY CREDIT RATING." "WHAT I DON'T KNOW IS WHY YOU'RE RATING ME." "I GAVE YOU A 10." "BENEVOLENT SEXISM, DON." "LOOK IT UP." "[ SIGHS ] CAN I START OVER?" "PLEASE." "I..." "FOUND OUR DREAM HOUSE." "WHOA." "PRETTY AMAZING, RIGHT?" "OKAY, REMIND ME." "WHEN DID WE DECIDE TO START HOUSE HUNTING?" "I'VE JUST BEEN POKING AROUND ON SOME REAL-ESTATE SITES" "JUST TO GET A SENSE OF THE MARKET." "I JUST FEEL LIKE WE'VE GOT ENOUGH ON OUR PLATES WITHOUT BUYING A HOUSE." "I'M NOT SAYING WE SHOULD BUY IT." "JUST TAKE A LOOK." "[ TELEPHONE RINGING ]" "MORETTI." "OKAY." "I'M ON MY WAY." "WE'RE GONNA HAVE TO TALK REAL ESTATE LATER." "WHY?" "WHAT'S GOING ON?" "BABY'S JUST BEEN KIDNAPPED." "[ POLICE RADIO CHATTER ]" "HE'S " " HE'S BEEN SO FUSSY LATELY" "THAT I DIDN'T WANT TO WAKE HIM," "SO I DECIDED I WOULD UNLOAD THE GROCERIES" "BEFORE I TOOK HIM OUT OF HIS CAR SEAT." "[ SNIFFLES ] OH, MY GOD." "HOW COULD I HAVE BEEN SO STUPID?" "LUCY, DON'T BLAME YOURSELF." "WE NEED TO FOCUS ON FINDING YOUR BABY." "NOW, HOW LONG WAS HE OUT OF YOUR SIGHT?" "A MINUTE." "TWO AT THE MOST." "BY THE TIME I SAT THE BAGS DOWN AND CAME BACK," "THE WINDOW WAS SMASHED AND HE WAS GONE!" "HANG IN THERE, OKAY?" "YOU'RE DOING GREAT." "NOW, EXACTLY HOW OLD IS OWEN?" "EIGHT WEEKS." "HE HAS BLUE EYES." "OH, HERE." "I HAVE A PICTURE OF HIM ON MY PHONE." "HE'S BEAUTIFUL." "OKAY, I'M E-MAILING THIS TO MYSELF NOW," "AND WE'RE GONNA CIRCULATE THIS" "TO ALL OF THE LOCAL LAW-ENFORCEMENT AGENCIES." "ANY KNOWN MEDICAL ISSUES?" "HE'S A LITTLE COLICKY." "OKAY." "AND WHO ELSE LIVES IN THE HOUSE?" "JUST ME AND OWEN." "AND THE BABY'S FATHER?" "HIS NAME'S ANDREW O'LEARY." "AND HAVE YOU BEEN IN CONTACT SINCE OWEN'S DISAPPEARANCE?" "I'M NOT SURE HOW TO GET AHOLD OF HIM." "HE'S NOT REALLY IN OUR LIVES ANYMORE." "I-I THOUGHT HE WANTED TO BE A F-FATHER, BUT HE WALKED OUT." "ANY IDEA WHERE HE MIGHT BE?" "HE'S " " HE'S A HUMVEE MECHANIC IN THE ARMY, IF THAT HELPS." "DON'T WORRY." "WE'LL FIND HIM." "NOW, WHEN YOU WERE OUTSIDE UNLOADING THE GROCERIES," "DID YOU SEE ANYONE?" "A GARBAGE COLLECTOR, MAIL CARRIER," "NEIGHBOR, ANYONE AT ALL?" "[ Voice breaking ] GOD, I DON'T KNOW." "THERE COULD HAVE BEEN SOMEONE," "BUT I WASN'T PAYING ATTENTION." "I'M SO STUPID!" "HAVE YOU SEEN ANY SUSPICIOUS PEOPLE" "OR VEHICLES IN THE NEIGHBORHOOD RECENTLY?" "WELL, I SAW A STRANGE CAR YESTERDAY." "IT WAS PARKED OUT IN FRONT." "AND THEN I SAW THAT SAME CAR" "SPEEDING UP THE STREET JUST A FEW HOURS AGO." "COULD YOU DESCRIBE THE CAR OR THE DRIVER?" "NO, I DIDN'T SEE THE DRIVER," "AND I'M NOT REALLY GOOD WITH CARS." "BUT I DID WRITE DOWN THE LICENSE-PLATE NUMBER" "JUST IN CASE." "HANG ON." "THANK YOU." "PUT OUT AN AMBER ALERT." "RIGHT AWAY." "SO, HOW WELL DO YOU KNOW LUCY HALPERN?" "WELL, SHE'S KIND OF THE QUIET, SHY TYPE." "STAYS TO HERSELF MOSTLY." "DO YOU EVER SEE HER WITH THE BABY?" "OH, YEAH." "SHE'S ALWAYS STROLLING HIM UP AND DOWN THE STREET HERE," "BUT SHE ALWAYS LOOKS SO EXHAUSTED." "I HALF WORRY SHE'S GONNA WANDER INTO TRAFFIC." "BOY, I'LL TELL YOU," "MOTHERHOOD IS NO PICNIC FOR THAT ONE, THAT'S FOR SURE." "OWENISONLY EIGHTWEEKSOLD." "PLEASE, IFTHEREIS ANYONEOUT THERE" "WHOHASANYINFORMATION ABOUTHISDISAPPEARANCE," "PLEASE,PLEASE HELPTHEPOLICEFINDHIM." "HENEEDSHISMOTHER." "IF THE PERSON WHO TOOK HIM IS WATCHING," "IDON'TCAREWHO YOU ARE ORWHYYOUDID IT." "[ Voice breaking ] I-IJUSTWANTHIM BACK!" "[ SOBS ]" "[ TELEPHONE RINGS ]" "LEWICKI, GET THAT." "DR. PIERCE'S RESIDENCE." "YEAH, RIGHT HERE." "IT'S KATE." "HEY." "HEY." "TURN ON CHANNEL 9?" "YEAH, WE'RE WATCHING IT." "COULD YOU COME OVER, TALK TO HER?" "FOR EMOTIONAL SUPPORT OR 'CAUSE YOU THINK" "SHE DID SOMETHING TO HER BABY?" "I DON'T KNOW, BUT IT WOULD BE HELPFUL" "IF YOU COULD..." "EVALUATE HER MENTAL HEALTH, DISCREETLY." "Daniel:" "YOU'VE GOT NOBODY TO -- TO HELP YOU," "NO FAMILY OR FRIENDS?" "NO, THERE'S JUST ME." "I CAN'T IMAGINE HOW HARD THAT MUST BE" "WITH ALL THE DIAPER CHANGES AND THE FEEDINGS AND THE CRYING." "YEAH." "DO YOU HAVE KIDS?" "NO." "NO." "SO, WHEN'S THE LAST TIME YOU HAD A FULL NIGHT'S REST?" "I DON'T KNOW." "PROBABLY NOT SINCE I BECAME A MOM." "CHRONIC SLEEP DEPRIVATION CAN WREAK HAVOC ON YOUR MOOD." "HAVE YOU BEEN FEELING IRRITATED OR ANGRY LATELY?" "WELL, YEAH, I GUESS A LITTLE." "YEAH, BUT WHO WOULDN'T FEEL A LITTLE FRUSTRATED" "TAKING CARE OF A SICK BABY ALL ALONE?" "OF COURSE." "WHAT DO YOU DO WHEN YOU FEEL FRUSTRATED?" "DO YOU THINK THAT I HURT MY OWN BABY?" "IS THAT WHAT THIS IS ABOUT?" "I'M NOT MAKING ANY ALLEGATIONS." "I'M JUST HERE TO HELP." "I WOULD NEVER HURT OWEN." "NEVER." "I WANT EVERYONE TO LAY BACK WHEN WE GET THERE." "LET ME MAKE THE FIRST APPROACH." "WE DON'T WANT TO SPOOK THE PERP." "ANY QUESTIONS?" "LET'S MOVE." "HEY, WHAT'S -- WHAT'S GOING ON?" "THE CAR THE NEIGHBOR I.D.'d WAS SPOTTED AT HEISE PARK." "HOW'D IT GO WITH LUCY?" "NOT GOOD." "TALK TO YOU WHEN I GET BACK." "EXCUSE ME, MISS?" "FBI." "I NEED TO SEE SOME IDENTIFICATION FROM YOU." "Woman:" "WHAT'S THIS ABOUT?" "MA'AM?" "Kate:" "MISS?" "STOP!" "FBI!" "[ INDISTINCT SHOUTING ]" "[ TIRES SCREECH ]" "[ PEOPLE SCREAM ]" "Woman:" "IS THE BABY ALL RIGHT?" "!" "SOMEBODY CALL AN AMBULANCE!" "SIR, IT'S OKAY." "WE DON'T NEED THE PARAMEDICS." "IT'S JUST A DOLL." "IT'S AMAZING HOW REAL THIS THING LOOKS." "HERE." "YOU WANT TO PRACTICE?" "OKAY, I DON'T KNOW WHAT'S CREEPING ME OUT MORE " "YOU OR THE DOLL." "ARE WE EVEN SURE THAT THIS IS LUCY'S BABY?" "YEAH." "SAME FACE." "LUCY'S GOT SOME 'SPLAININ' TO DO." "I HAVE AN AGENT BRINGING HER IN." "WHAT ABOUT THE DOLLNAPPER?" "FIGURED I'D CALL C.P.D., HAND HER OVER FOR LARCENY." "WELL, HANG ON A SEC." "IF BETSY WAS FOOLED BY THE DOLL LIKE WE ALL WERE" "AND HER ORIGINAL INTENT WAS TO STEAL A CHILD," "I COULD STILL PROSECUTE HER FOR KIDNAPPING." "I KNEW IT WAS A DOLL ALL ALONG." "I KNOW HOW CRAZY I MUST SEEM, BUT I COULDN'T HELP IT." "I HAD TO TAKE HIM." "WHY?" "SIX MONTHS AGO..." "I HAD A BABY." "CODY." "[ SNIFFLES ]" "HE WAS A BORN WITH A CONGENITAL HEART DEFECT." "HE ONLY SURVIVED SEVEN WEEKS." "I'M SO SORRY FOR YOUR LOSS." "I'VE BEEN HAVING A REALLY HARD TIME" "FIGURING OUT WHAT TO DO WITH MYSELF." "ITOLDMY THERAPIST THAT I'M ALWAYS FEELING" "THIS OVERWHELMING NEED TO JUST HOLD HIM AGAIN." "SHE SUGGESTED I GET A REBORN." "THEY'RE CRAFTED TO LOOK AS LIFELIKE AS POSSIBLE." "SOME WOMEN GET REALLY INTO THEM." "IN WHAT WAY?" "BUY THEM CLOTHES AND TOYS" "AND [SNIFFLES] HAVE BABY SHOWERS." "THEY TREAT THE DOLLS LIKE THEY'RE REAL?" "BUT FOR ME, IT WAS " "IT WAS JUST SUPPOSED TO BE A GRIEVING TOOL." "MYTHERAPISTSAID THATIFIHELDONE" "FOR A FEW MINUTES EACH DAY, ITMIGHTHELP." "AND AS..." "BIZARRE AS THAT SOUNDS," "I WAS WILLING TO TRY ANYTHING." "SO THAT'S WHY YOU STOLE LUCY'S DOLL?" "WELL, IT'S -- IT'S NOT HERS." "IT'S MINE." "I'D HEARD ABOUT THIS DOLLMAKER." "ASGAR SVENSDEN." "HE'S THE BEST REBORN ARTIST IN THE STATE." "I ASKED HIM IF HE COULD MAKE ONE TO LOOK LIKE MY SON." "HE SAID IT WOULD COST $4,500." "I HAD TO PUT DOWN A NON-REFUNDABLE DEPOSIT." "BUT I HAD A HARD TIME COMING UP WITH THE REST." "AND BY THE TIME I DID," "ASGAR HAD ALREADY SOLD MY DOLL TO SOMEONE ELSE." "I COULDN'T BELIEVE IT." "I MEAN, HOW CAN HE GIVE MY BABY TO ANOTHER WOMAN?" "IT'S NOT YOUR BABY." "IT'S MY DOLL." "I MADE IT." "I OWN IT." "I CAN SELL IT." "I REALIZED THAT IT WAS POINTLESS TO ARGUE WITH HIM," "SO I JUST ASKED HIM FOR THE BUYER'S NAME AND ADDRESS." "AND HE GAVE IT TO YOU?" "IT TOOK SOME CONVINCING," "BUT, YEAH, I FINALLY GOT IT." "I JUST WANTED TO TALK TO HER, TRY TO EXPLAIN." "BUT I SAW CODY STRAPPED IN THE CAR." "ASGAR SAID YOU'RE NOT SUPPOSED" "TO LEAVE THE DOLLS IN HOT CARS" "BECAUSE THE PAINT CAN WARP AND THE VINYL CAN MELT." "AND AS CRAZY AS IT SOUNDS, I COULDN'T STAND IT." "I HAD TO RESCUE HIM." "[ CAR DOOR UNLOCKS ]" "[ SCOFFS ]" "NEVER OCCURRED TO ME THAT LUCY MIGHT CALL THE FBI." "HOW MUCH TROUBLE AM I IN?" "I'M NOT GOING TO PROSECUTE A GRIEVING MOTHER," "BUT THAT WOMAN'S THERAPIST IS A WACKO." "WHO TELLS SOMEONE TO USE A DOLL" "TO GET OVER THEIR DEAD BABY?" "WELL, SOMETIMES PEOPLE HAVE TO DO" "WHATEVER GETS THEM THROUGH THE NIGHT." "SURE, BUT IT SOUNDS LIKE SOME OF THESE WOMEN" "ARE TAKING THIS STUFF TOO FAR." "YEAH, LIKE SOMEONE WHO REPORTS A KIDNAPPING" "BECAUSE HER DOLL WAS STOLEN?" "NOW, LUCY OBVIOUSLY KNEW IT WASN'T REAL," "BUT SINCE THE FBI DOESN'T FIND TOYS," "SHE LIED AND SAID THAT HER BABY WAS MISSING." "I'M GONNA CHARGE HER FOR KNOWINGLY FILING A FALSE REPORT." "WAIT." "T-THERE MIGHT BE MORE TO IT THAN THAT." "LET ME -- LET ME TALK TO HER." "[ GASPS ] OH, MY GOD!" "[ LAUGHS ]" "OH, MOMMY'S SO SORRY!" "[ SNIFFLES ]" "I'LL NEVER LEAVE YOU ALONE AGAIN." "JUST GLAD THE FBI WAS ABLE TO HELP." "WOULD YOU LIKE TO SIT DOWN FORA MINUTE?" "GETYOURBEARINGS?" "YEAH." "SURE." "[ SIGHS ]" "HI, BABY." "YOU'RE GOOD WITH HIM." "OH." "I DO MY BEST." "LUCY, DO YOU KNOW SOMEONE NAMED ASGAR SVENSDEN?" "YEAH, HE'S SUCH A NICE MAN." "WHAT IS YOUR RELATIONSHIP WITH HIM?" "HE ARRANGED THE ADOPTION." "I DIDN'T REALIZE THAT OWEN WAS ADOPTED." "IT WAS THE ONLY WAY I COULD BE A MOTHER." "OH." "UH-OH." "[ CHUCKLES, SNIFFLES ] SOMEBODY MADE A POOPY." "DOYOUMINDIFI CHANGEHIM WHILEWETALK?" "NOTATALL." "LUCY IS SUFFERING FROM DELUSIONAL DISORDER." "IT'S A PSYCHIATRIC CONDITION" "IN WHICH A PATIENT HOLDS A FIXED DELUSION," "BUT HAS NO OTHER OBVIOUS PROBLEMS WITH THOUGHT OR MOOD." "I DECIDED TO DROP THE CASE DURING THE DIAPER CHANGE." "ARE YOU SURE WE'RE DOING THE RIGHT THING" "BY GIVING THE DOLL BACK TO HER?" "TAKING IT AWAY NOW WOULD ONLY WORSEN HER MENTAL STATE." "HOPEFULLY OVER TIME SHE'LL RESPOND" "TO A COMBINATION OF DRUGS AND PSYCHOTHERAPY." "SHOULD WE CALL THE HOSPITAL, TRY AND GET HER ADMITTED?" "NO, NO, NO." "LISTEN, SHE'S GOT A SINGLE FIXED DELUSION," "BUT IT'S NOT HAMPERING HER ABILITY TO FUNCTION." "SENDING HER TO A HOSPITAL WOULD ONLY MAKE THINGS WORSE." "AND, AS YOU KNOW, WE HAVE NO AUTHORITY TO COMMIT HER." "WE JUST SEND HER HOME?" "I'LL MAKE SURE SHE SEES A DOCTOR FIRST THING IN THE MORNING." "Natalie:" "I NEED A PICKLE." "WHAT THE HELL?" "I WAS THINKING HARPER IF IT'S A GIRL AND KEITH IF IT'S A BOY." "WHAT DO YOU THINK?" "I THINK THE SIGHT OF YOU EXPECTING IS..." "VERY UNEXPECTED." "WELL, YOU OBVIOUSLY HAVE BABIES ON THE MIND." "AFTER TODAY'S CASE, HOW COULD I NOT?" "DANIEL, WE BOTH KNOW THERE'S ANOTHER REASON" "WHY YOU'RE SEEING ME THIS WAY." "WHICH IS?" "YOU WANT A BABY." "WHAT?" "!" "ARE YOU OUT OF YOUR MIND?" "[ Laughing ] I DON'T WANT A BABY." "WELL, CONSIDERING MY CURRENT STATE," "I FIND IT HARD TO BELIEVE." "THE CRYING AND THE DIRTY DIAPERS" "AND " " AND " " AND THE COMPLETE HAVOC" "BABIES WREAK ON ANY SEMBLANCE OF A SCHEDULE?" "NO, THANK YOU." "WELL, WHAT ABOUT THE GOOD STUFF?" "THE FEELING OF A BABY SLEEPING IN YOUR ARMS," "THE WAY THEY LAUGH." "IT'S OUT OF THE QUESTION." "WHY?" "YOU KNOW WHY." "I WOULD NEVER RISK PASSING THIS ON TO A CHILD." "IT'S BETTER NOT TO BE BORN THAN TO BE BORN WITH SCHIZOPHRENIA?" "THERE IS NO WAY YOU ARE DRAGGING ME" "INTO THAT PHILOSOPHICAL QUAGMIRE." "OOH." "WHAT?" "THE BABY'S KICKING." "YOU WANT TO FEEL?" "THIS IS TOO CRAZY, EVEN FOR ME." "IT'S NOT CRAZY" "TO CONSIDER WHAT LIFE WOULD BE LIKE WITH A BABY." "IT'S PERFECTLY NORMAL." "SAID THE PREGNANT HALLUCINATION." "YOU'RE NO FUN." "GO EAT A PICKLE." "Donnie:" "BAKERS MARBLE COUNTERTOPS, ABUNDANT NATURAL LIGHT." "WHAT'S NOT TO LOVE?" "WHAT WOULD WE DO WITH FOUR BEDROOMS ANYWAY?" "WELL, THE MASTER IS FOR US, A NURSERY, A GUEST ROOM," "AND THE FOURTH GIVES US ROOM TO GROW." "HERE." "LOOK." "LOOK AT THAT YARD." "HOW PERFECT IS THAT FOR KIDS?" "PUT A BIG SWING SET IN," "BIRTHDAY PARTIES, EASTER-EGG HUNTS." "PLUS IT'S IN A GREAT SCHOOL DISTRICT," "SO I THINK IT'S GONNA GO REALLY FAST." "YOU DID RESEARCH ON THE SCHOOL DISTRICT?" "YEAH." "GUESS MY BIOLOGICAL CLOCK IS TICKING." "ISN'T YOURS?" "WELL, YEAH." "I MEAN, I GUESS WE ARE AT THAT AGE." "SLOW DOWN, SAILOR." "IT'S GONNA BE A LONG VOYAGE." "I MEAN, REALLY, WE ARE HAVING A TRADITIONAL CATHOLIC WEDDING." "I'M NOT WALKING DOWN THE AISLE WITH A BABY BUMP, OKAY?" "[ CELLPHONE RINGS ]" "HELLO?" "I'LL BE RIGHT THERE." "WHAT'S WRONG?" "I JUST WANTED TO SEE HOW SHE WAS DOING." "OH." "[ POLICE RADIO CHATTER ]" "WHERE IS SHE?" "[ CAMERA SHUTTER CLICKING ]" "WHAT DO YOU GOT?" "MURDER WEAPON." "WELL, THAT'S A NEW ONE." "WHAT THE HELL HAPPENED?" "WHO DID THIS?" "I DON'T KNOW, BUT THE DOLL IS MISSING." "[ SIGHS ]" "WELL, WHAT'S HER NAME, BETSY, SHE " " SHE STOLE IT ONCE." "MAYBE -- NO, IT WASN'T HER." "SHE LEFT TOWN FOR HER SISTER'S AS SOON AS WE CUT HER LOOSE." "ANY SIGNS OF FORCED ENTRY?" "NO, BUT I MIGHT HAVE ANOTHER LEAD." "WHAT'S THAT?" "LUCY'S BABY DADDY." "SHE SAID THAT HE WALKED OUT ON HER." "WE TRACKED HIM DOWN TO A MILITARY BASE" "ABOUT THREE HOURS AWAY." "HE JUST GOT BACK FROM AFGHANISTAN." "I MET LUCY ABOUT SIX MONTHS BEFORE I GOT DEPLOYED." "I WAS AT A GAS STATION IN MY DRESS BLUES." "SHE CAME OVER TO THANK ME FOR MY SERVICE." "[ CHUCKLES ]" "I TOLD HER I'D NEVER BEEN THANKED BY A WOMAN SO PRETTY BEFORE." "HER WHOLE FACE WENT RED." "I ASKED HER OUT RIGHT THEN." "AND HOW LONG WERE YOU TOGETHER?" "ABOUT A YEAR AND A HALF." "I WAS CRAZY ABOUT HER." "SHE'D BEEN WITH A LOT OF JERKS WHO TREATED HER LIKE DIRT." "BUT I TREATED HER THE WAY SHE DESERVED." "HOW SERIOUS DID THINGS GET?" "I POPPED THE QUESTION BEFORE I GOT DEPLOYED." "SHE SAID YES?" "SHE SAID SHE'D BE COUNTING THE DAYS" "UNTIL I CAME HOME." "I TOLD HER WE'D BUY A HOUSE," "MAKE BEAUTIFUL BABIES TOGETHER." "ONLY A MONTH INTO MY DEPLOYMENT," "SHE SKYPED ME AND TOLD ME SHE WAS ALREADY PREGNANT." "HOW'D YOU TAKE THE NEWS?" "GUYS!" "I'M GONNA BE A DAD!" "[ MEN CHEERING ]" "I SENT HER MONEY OUT OF MY PAY FOR DOCTOR BILLS," "NURSERY STUFF." "I WAS IN LOVE WITH THAT KID BEFORE I EVEN MET HIM." "I WAS BUMMED WHEN I MISSED HIS BIRTH." "SO MY FRIENDS, THEY THREW ME A PARTY." "AND THE BEST GIFT CAME FROM MY C.O." "TRANSFERRED ME BACK STATESIDE" "SO I COULD GO HOME AND SEE MY SON." "I DIDN'T TELL LUCY THAT I WAS COMING" "BECAUSE I WANTED TO SURPRISE HER." "HEY." "WHAT THE HELL?" "ANDREW." "WHERE'S OWEN?" "I CAN EXPLAIN." "EXPLAIN WHAT?" "THAT YOU LIED TO ME?" "LOOK, NO." "OH, MY GOD." "TELL ME THIS IS NOT HAPPENING!" "TELL ME THIS IS SOME SORT OF A JOKE!" "PLEASE." "DON'T TOUCH ME!" "I WAS SUCH AN IDIOT." "ALL THAT BULLSHIT" "ABOUT THE DOCTOR BILLS, THE NURSERY STUFF." "SHE WAS JUST SCAMMING ME FOR MONEY THE WHOLE TIME." "IT WASN'T ABOUT THE MONEY, SERGEANT." "LUCY WAS A PSYCHOLOGICALLY FRAGILE WOMAN." "SHE TOLD ME SHE COULDN'T HAVE CHILDREN." "MAYBE SHE LIED ABOUT THE PREGNANCY" "BECAUSE SHE WAS AFRAID OF LOSING YOU." "I JUST DON'T UNDERSTAND HOW SHE COULD TAKE IT SO FAR." "IT'S ONE THING TO LIE ABOUT BEING PREGNANT," "BUT TO TRY TO FAKE ME OUT WITH A DOLL?" "I THINK SHE USED THE DOLL TO PERPETUATE THE LIE," "BUT AT SOME POINT, IT BECAME REAL FOR HER." "BUT THAT DOESN'T EXPLAIN" "WHY SHE WOULD HAVE TOLD ANDREW THAT SHE WAS PREGNANT" "AND TELL US THAT OWEN WAS ADOPTED." "WAIT." "ADOPTED?" "WHEN YOU WALKED OUT, SHE WAS PROBABLY DEVASTATED" "AND " " AND TURNED TO THE ONLY SOURCE OF COMFORT" "THAT SHE HAD AVAILABLE TO HER." "THE DOLL." "YES." "THAT'S WHEN HER FANTASY OF BEING A MOTHER" "BECAME A FULL-BLOWN DELUSION." "SHE GRABBED ON TO THE IDEA OF ADOPTION BECAUSE IT WAS LESS PAINFUL" "THAN THINKING OF YOU AS THE BIOLOGICAL FATHER." "IT'S ALL MY FAULT." "IF I'D HAVE GOTTEN HER HELP, MAYBE SHE'D STILL BE ALIVE." "NO, SERGEANT." "LUCY'S MENTAL ILLNESS MOST LIKELY BEGAN" "LONG BEFORE SHE MET YOU." "WHAT DO YOU KNOW ABOUT HER CHILDHOOD?" "LUCY DIDN'T LIKE TO TALK ABOUT HER CHILDHOOD MUCH." "BUT I KNOW HER MOTHER BEAT THE HELL OUT OF HER GROWING UP." "WHEN WAS THE LAST TIME YOU SAW YOUR DAUGHTER?" "TWO MONTHS AGO." "IF I'D KNOWN I'D NEVER SEE HER AGAIN," "I WOULD HAVE TOLD HER I LOVED HER." "WHAT HAPPENED THE LAST TIME YOU SPOKE?" "[ SIGHS ]" "SHE WASN'T EXPECTING ME." "SHE CAME TO THE DOOR HOLDING A BABY." "I ASKED WAS SHE BABYSITTING OR SOMETHING." "AND SHE SAID, NO, THE KID WAS HERS." "I COULDN'T BELIEVE IT." "I DIDN'T EVEN KNOW SHE WAS PREGNANT." "SO THEN WHAT HAPPENED?" "WELL, SHE WAS LOOKING KIND OF RUN-DOWN." "I TOLD HER TO GO DO SOMETHING NICE FOR HERSELF, YOU KNOW?" "TAKE A BREAK." "I'D WATCH THE LITTLE STINKER." "SHE SAID SHE COULDN'T TRUST ME." "WITH A DOLL?" "WHAT DO YOU MEAN, A DOLL?" "WE'RE TALKING ABOUT MY GRANDBABY, OWEN." "WAIT A MINUTE." "ARE YOU SAYING YOUR DAUGHTER HAD A REAL BABY?" "OF COURSE SHE HAD A REAL BABY." "THE DAMN THING PUKED ALL OVER ME." "THANK YOU." "WELL, THE M.E. CONFIRMED" "LUCY RECENTLY GAVE BIRTH." "SO SHE AND SERGEANT WHAT'S-HIS-NAME" "REALLY DID HAVE A CHILD TOGETHER." "BUT AT SOME POINT," "SHE SWITCHED OUT THE REAL INFANT FOR A DOLL." "WHY?" "[ SIGHS ]" "[ BABY CRYING ]" "DID -- DID YOU HEAR THAT?" "HEAR WHAT?" "NEVER MIND." "I CAN'T WATCH THIS ANYMORE." "I'LL BE INSIDE." "[ BABY CRYING ]" "[ LID CLATTERS ]" "THEY SWEPT THE WHOLE HOUSE AND THE YARD." "BODY'S NOT HERE." "LOOK AT THIS." "IT'S A TREASURE BOX." "SOUVENIRS." "ALWAYS TURNS MY STOMACH" "WHEN KILLERS KEEP THOSE." "I DON'T KNOW." "[ STAMMERS ]" "LOOK AROUND." "L-LOOK AT THIS NURSERY." "LOOK HOW WELL IT'S KEPT." "I " "EVERYTHING I'M SEEING TELLS ME SHE LOVED HER BABY." "I'M SURE SHE DID." "NO, NO, WHAT I MEAN IS I DON'T THINK SHE KILLED HIM." "LOOK, WE -- WE KNOW HER MOM WAS ABUSIVE." "THAT DOESN'T MEAN SHE BECAME ABUSIVE." "YOU KNOW, MAYBE SHE " "MAYBE SHE WAS AFRAID OF BEING A MOTHER" "AND SH-- AND SHE GAVE THE BABY AWAY." "LOOK, I'M NOT CALLING THE DOGS OFF YET " " LITERALLY " "BUT YOU'RE RIGHT." "WE SHOULD CHECK IN WITH SOCIAL SERVICES," "SEE IF THEY KNOW ANYTHING." "Woman:" "MALE INFANT, NEWBORN CAUCASIAN," "WAS RELINQUISHED AT A LOCAL FIRE STATION ABOUT A MONTH AGO." "GREAT." "SO WHERE " " WHERE IS HE?" "IN FOSTER CARE?" "SAYS HERE A CASE WORKER RESPONDED" "BUT WAS TOLD IT WAS A FALSE ALARM." "WHAT DOES THAT MEAN?" "THAT'S ALL I HAVE." "SO NOBODY ASKED ANY QUESTIONS?" "THE WHOLE POINT TO THE SAFE HAVEN LAW" "IS SO THAT PARENTS CAN GIVE UP A NEWBORN" "WITHOUT ANY QUESTIONS ASKED." "IF THEY HAD TO GIVE UP THEIR NAME, RANK," "AND SERIAL NUMBER, NO ONE WOULD DO IT." "CAN YOU TELL US WHAT FIRE STATION?" "YEAH, THAT'S HER." "CAN YOU EXPLAIN EXACTLY WHAT HAPPENED WHEN SHE CAME IN?" "IT WAS LATE, MAYBE 2:00 A.M." "EVERYONE ELSE HAD GONE OUT ON CALL," "SO I WAS THE ONLY ONE HERE." "SHE WAS PRETTY SHAKEN UP WHEN SHE CAME IN." "LOOKED LIKE SHE'D BEEN CRYING AWHILE." "I MEAN, SHE JUST HANDED ME THE BABY AND LEFT." "SO YOU CALLED DCFS?" "YEAH." "BUT TOOK AWHILE FOR THE SOCIAL WORKER TO GET HERE." "SO I JUST HELD THE BABY, TRIED TO KEEP HIM CALM." "CUTEST LITTLE BUGGER I EVER SAW." "SO THEN WHAT HAPPENED?" "WELL, NEXT THING I KNOW," "HIS MOM COMES WALKING BACK THROUGH THE DOOR." "WHAT DID SHE SAY?" "THAT SHE MADE A MISTAKE," "THAT SHE'D GIVEN HIM TO ME" "BECAUSE SHE WAS FEELING OVERWHELMED." "SHE TALKED TO HER FAMILY, AND THEY WERE GONNA HELP HER OUT." "SO WHAT DID YOU DO?" "WHAT COULD I DO?" "I FELT SORRY FOR HER." "SHE WAS OBVIOUSLY GOING THROUGH A HARD TIME." "AND I KNEW THAT ONCE HER KID WAS IN THE SYSTEM," "SHE'S GONNA HAVE A HELL OF A TIME GETTING HIM BACK." "SO I GAVE HIM BACK." "BUT YOU HAD ALREADY CALLED DCFS." "I MEAN -- I KNOW." "I KNOW." "I SCREWED UP." "I SHOULD HAVE STALLED HER" "TILL THE SOCIAL WORKER GOT HERE." "I JUST DIDN'T WANT TO MAKE THINGS HARDER ON HER." "DID SOMETHING BAD HAPPEN TO THAT BABY?" "IF LUCY HAD SOME SORT OF A SCARE" "THAT PROMPTED HER TO GIVE UP HER BABY," "BUT THEN SHE CAME BACK" "SAYING THAT FAMILY PROMISED TO HELP, THEN MAYBE " "MAYBE SHE WAS TALKING ABOUT HER MOM." "MAYBE SHE DID AGREE TO LET HER BABYSIT." "I MEAN, IT'S NOT INCONCEIVABLE" "THAT SHE KILLED HER OWN GRANDCHILD." "WHICH WOULD HAVE TRIGGERED LUCY'S PSYCHOSIS." "BUT THEN WHAT?" "MOTHER KILLS DAUGHTER?" "WHY?" "WELL, EITHER SHE WAS NERVOUS THAT LUCY" "WOULD TELL THE COPS SHE KILLED OWEN" "OR IT WAS ABOUT THE DOLL." "OKAY, YOU LOST ME THERE." "WELL, DON'T FORGET, IT'S MISSING." "AND IT'S WORTH A LOT OF MONEY." "I'LL SCOUR THE INTERNET AND THE LOCAL PAWNSHOPS," "SEE IF MOMMY DEAREST MIGHT BE TRYING TO SELL IT." "[ DOORBELL RINGS ]" "LEWICKI!" "[ DOORBELL RINGS ]" "LEWICKI!" "[ BABY COOING ]" "LEWICKI!" "[ BABY CRYING ]" "LEWICKI!" "YOU " " YOU -- YOU CALLING FOR ME, DOC?" "YES, I'M CALLING YOU." "I NEED SOME HELP HERE WITH THIS BABY." "WHAT BABY, DOC?" "NOTHING." "GO " " GO BACK TO BED, LEWICKI." "YOU'RE HAVING A NIGHTMARE." "OR I AM." "[ SCOFFS ]" "[ SIGHS ]" "[ BABY COOING ]" "[ NATALIE HUMMING ]" "IT'S NOT GONNA BITE." "WHO KNOWS WHERE MY SCHIZOPHRENIC BRAIN" "IS GONNA TAKE THIS." "OH, PLEASE." "ON SOME LEVEL, YOU WANT TO BE A FATHER," "OR YOU WOULDN'T BE HALLUCINATING A BABY." "THE VERY FACT THAT I AM" "IS EXACTLY WHY IT'S NOT SAFE FOR ME TO BE A PARENT." "IS THAT WHY YOU DON'T WANT KIDS?" "BECAUSE YOU DON'T THINK IT'S SAFE?" "I COULD NEVER FORGIVE MYSELF IF " "IF WHAT?" "I HAVE TO SPELL IT OUT FOR YOU?" "M-M-ME AND JUNIOR ARE PLAYING CATCH IN THE YARD ONE DAY" "AND " " AND SUDDENLY I START TALKING" "TO A FIGMENT OF MY IMAGINATION" "WHILE MY CHILD CHASES A BALL INTO THE STREET." "OR " " OR I-I LEAVE MY KID WITH A BABYSITTER" "AND SOMETHING HORRIBLE HAPPENS" "BECAUSE THE SITTER I HIRED WAS ALL IN MY HEAD." "DANIEL, YOU'VE DONE A GREAT JOB" "AT DEVELOPING COPING STRATEGIES TO KEEP YOURSELF SAFE." "IF YOU REALLY WANT TO BE A DAD, MAYBE YOU CAN ADOPT." "YEAH. [ CHUCKLES ] THAT'S A GREAT IDEA." "PSYCHOTIC SINGLE PROFESSOR IN HIS LATE 40s LOOKING TO ADOPT." "I THINK YOU'RE BEING HARD ON YOURSELF." "AND YOU ARE BEING UNREALISTIC." "A BABY IS OUT OF THE QUESTION." "THEN WHY ARE YOU HALLUCINATING ONE?" "MAYBE MY BRAIN'S JUST TRYING TO TELL ME SOMETHING." "WHAT?" "WHAT ARE YOU TRYING TO TELL ME?" "YEAH, YEAH, YOU'RE VERY GOOD AT BEING CUTE," "BUT I'M GONNA NEED MORE HELP THAN THAT." "[ CHUCKLES ] I KNOW WHAT YOU'RE DOING." "I KNOW WHAT YOU'RE DOING." "YOU'RE A VERY CUTE BABY" "WITH A HEAD AND EYES TOO LARGE FOR YOUR BODY," "AND RIGHT NOW, I CAN'T HELP BUT FEEL ATTACHED" "BECAUSE YOU'RE CAUSING DOPAMINE TO FLOOD MY NUCLEUS ACCUMBENS." "I KNOW ALL ABOUT THE SCIENCE OF CUTENESS," "YOU MANIPULATIVE, LITTLE RUNT." "THE VERY ESSENCE OF YOUR SURVIVAL" "LIES IN YOUR ABILITY TO STIMULATE" "THE GENETICALLY PROGRAMMED PROTECTIVE MECHANISMS" "OF THOSE AROUND YOU." "WELL, IT'S NOT GONNA WORK." "[ BABY COOS ]" "[ POLICE RADIO CHATTER ]" "WHAT'S GOING ON?" "PLEASE STEP OUTSIDE." "NO." "NOT UNTIL YOU TELL ME " "DO NOT MAKE THIS ANY HARDER THAN IT NEEDS TO BE." "STEP OUTSIDE." "[ BABY COOING ]" "[ EMMA SOBS ]" "OH, MY GOD." "PLEASE STOP THEM." "PLEASE." "PLEASE DON'T TAKE OUR BABY." "IT'S NOT YOUR BABY." "[ SOBBING ]" "Scott:" "EMMA AND I TRIED FOR YEARS TO GET PREGNANT." "IVF, FERTILITY DRUGS." "WE EVEN CONSIDERED A SURROGATE AT ONE POINT." "THEN LUCY COMES WALKING UP TO THE STATION." "SHE TOLD ME THAT SHE NEVER THOUGHT" "SHE'D BE CAPABLE OF HARMING HER OWN BABY," "BUT AN HOUR EARLIER," "SHE FOUND HERSELF ON THE VERGE OF SHAKING HIM." "AND I TOLD HER SHE DIDN'T HAVE TO GIVE UP THE BABY," "THAT SHE COULD GET HELP," "THAT THE IMPORTANT PART HERE WAS THAT SHE DIDN'T HARM HER BABY." "SHE SAID THAT SHE -- SHE COULDN'T TAKE ANY CHANCES." "SHE JUST TOOK OFF." "I CALLED DCFS AS SOON AS SHE LEFT." "THEN YOU SAT THERE WAITING, STARING AT OWEN," "THINKING ABOUT THE LIFE THAT HE'D HAVE IN FOSTER CARE." "WHAT'D YOU SAY?" "THE CUTEST, LITTLE BUGGER YOU EVER SAW?" "I COULDN'T TAKE IT." "HE DESERVES STABILITY" "AND A MOTHER AND FATHER WHO LOVE HIM." "SO WHEN THE SOCIAL WORKER SHOWED UP," "YOU LIED AND SAID THAT THE MOTHER HAD COME BACK." "LOOK, I KNOW I DIDN'T HANDLE EVERYTHING PERFECTLY," "BUT I SAVED THAT BABY." "NO, LUCY SAVED HER BABY." "SHE WAS AFRAID SHE WAS GONNA BECOME LIKE HER MOTHER," "AND SOMEHOW SHE FOUND THE STRENGTH TO DO THE RIGHT THING." "YOU, ON THE OTHER HAND," "TOOK SOMETHING THAT DIDN'T BELONG TO YOU." "I BELIEVE IT'S CALLED KIDNAPPING." "BUT YOU DID A WHOLE LOT MORE THAN THAT, DIDN'T YOU?" "WHAT?" "WHAT " " WHAT ARE YOU -- WHAT ARE YOU TALKING ABOUT?" "OH, COME ON, SCOTT." "YOU STOLE HER BABY," "AND THEN YOU KILLED HER TO COVER IT UP." "WHAT?" "YOU SAW LUCY ON THE NEWS" "SAYING THAT HER BABY HAD BEEN ABDUCTED." "YOU WERE AFRAID THAT SHE WAS GONNA TELL THE COPS" "THAT OWEN WAS WITH YOU." "NO." "NO, I WILL ADMIT THAT ME AND EMMA GOT SCARED" "WHEN WE SAW HER ON THE NEWS." "THE NEXT THING WE KNOW, SHE'S DEAD." "AND WE JUST FIGURED THAT THE SECRET DIED WITH HER." "YOU BUYING IT?" "I DON'T KNOW." "ME NEITHER." "I MEAN, IF HE DID WANT TO KILL LUCY" "TO KEEP HER FROM TALKING, WHY USE A TOY TRUCK?" "IT'S AN ODD CHOICE FOR A MURDER WEAPON." "WELL, MAYBE HE DIDN'T GO OVER THERE TO KILL HER." "MAYBE HE WENT TO TALK TO HER, THINGS GOT HEATED," "HE GRABBED THE CLOSEST THING TO HIM," "AND HE HIT HER WITH IT." "[ BABY CRYING ]" "DANIEL?" "WHAT'S GOING ON?" "MAYBE THIS ISN'T ABOUT THE BABY." "MAYBE IT'S ABOUT THE DOLL." "WE'RE HERE TO MAKE A BABY." "YOU'VE COME TO THE RIGHT PLACE." "I SPEND HUNDREDS OF HOURS ON EACH OF MY CREATIONS." "IT SEPARATES ME FROM OTHER REBORN ARTISTS." "EVERY TINY VEIN AND BIRTHMARK AND MILK SPOT" "IS HAND-PAINTED WITH EXQUISITE ATTENTION TO DETAIL." ""CONGRATULATIONS ON BECOMING A PROUD PARENT" ""OF AN ADOPTED REBORN." ""YOUR CHILD IS NOT A TOY BUT A DELICATE HEIRLOOM" ""THAT WILL BRING DECADES OF JOY" "TO YOU AND YOUR FAMILY IF PROPERLY MAINTAINED."" "HON?" "HMM?" "GET A LOAD OF ALL THESE RULES." ""DON'T SMOKE AROUND THE BABY." SURE." ""DON'T BATHE IT, DON'T PULL TOO HARD ON ITS LIMBS," ""DON'T WEAR LOTION WHEN HANDLING IT," ""DON'T LEAVE DOGS ALONE WITH IT" "LEST THEY MISTAKE IT FOR A CHEW TOY."" "WOW." "THIS MIGHT BE HARDER THAN TAKING CARE OF AN ACTUAL BABY." "NO, NO, NO." "KEEP IN MIND THAT EACH OF MY CREATIONS" "IS A ONE-OF-A-KIND COLLECTORS ITEM" "THAT REQUIRES PROTECTIVE CARE." "SO, YES, THERE ARE SOME RESPONSIBILITIES INVOLVED." ""JUST LIKE A REAL NEWBORN," ""YOUR BABY SHOULD BE KEPT SAFE FROM EXTREME HEAT AND COLD." ""NEVER LEAVE YOUR BABY IN A HOT CAR." ""IF YOU EVER FIND YOURSELF IN NEED OF REPAIRS," ""PLEASE DO NOT HESITATE TO CONTACT ME." ""AS YOUR BABY'S MAKER," "I CONSIDER MYSELF A COMMITTED GODPARENT."" "CAREFUL." "[ CHUCKLES ]" "RIGHT." "I DON'T KNOW, HON." "THESE THINGS JUST KIND OF SEEM LIKE A PAIN IN THE ASS." "MAYBE WE SHOULD JUST GET A DOG." "AAH!" "NO, NO, NO!" "YOU MUSTN'T HANDLE THE DOLL SO ROUGHLY." "THEY'RE WEIGHTED LIKE REAL INFANTS." "YOU CAN BREAK THE NECK HOLDING IT SO THOUGHTLESSLY." "TAKE A PILL, MAN." "IT'S JUST A DOLL." "GET OUT." "YOU DON'T DESERVE ONE OF MY CREATIONS." "AND IS THAT HOW YOU FELT ABOUT LUCY HALPERN?" "THAT SHE DIDN'T DESERVE ONE OF YOUR CREATIONS?" "WHAT IS THIS?" "SPECIAL AGENT KATE MORETTI, FBI." "THIS IS A MURDER INVESTIGATION." "WE DUSTED THE CRIME SCENE FOR PRINTS." "WE GOT SOME PRETTY CLEAN REMNANTS ON THAT TOY TRUCK." "UNLESS YOU HAVE A WARRANT, I WOULD LIKE YOU TO LEAVE." "LUCY DIDN'T TAKE CARE OF THAT DOLL, DID SHE?" "HOW WOULD I KNOW?" "YOU PUT YOUR WHOLE BEING INTO THAT DOLL." "YOU BREATHED LIFE INTO IT." "YOU COULDN'T HAVE FELT MORE CONNECTED" "IF IT REALLY WAS YOUR OWN CHILD." "AND LUCY WAS AN UNFIT MOTHER, WASN'T SHE?" "WHEN I SAW HER ON THE NEWS, I REALIZED SHE'D LOST HER MIND." "AND IF SHE WAS STUPIDLY TREATING THE DOLL LIKE A REAL INFANT," "THEN SHE WAS SURELY RUINING IT!" "SO I DECIDED TO PAY HER A HOUSE CALL." "THE PAINT JOB WAS SUFFERING FROM TOO MUCH SUNLIGHT." "I ALSO NOTICED A CRACK AT THE BASE OF THE HEAD" "AND MILDEW ON THE TORSO." "SHE'D OBVIOUSLY BEEN BATHING THE DOLL." "GOD KNOWS WHAT ELSE WITH IT." "I WAS INCENSED TO FIND THE DOLL IN SUCH POOR CONDITION." "I TOLD HER I SHOULD NEVER HAVE SOLD IT TO HER" "IN THE FIRST PLACE." "I WAS GOING TO GIVE HER MONEY BACK." "PLEASE." "PLEASE DON'T TAKE MY BABY." "I WARNED HER THAT SHE WAS GOING TO DESTROY IT" "IF SHE KEPT PULLING, BUT SHE WOULDN'T STOP!" "I WAS UP ALL NIGHT TRYING TO REPAIR THE DAMAGE." "BUT NOW..." "OH." "IT'S PERFECT." "YOU KILLED A WOMAN..." "OVER A DOLL." "IT'S -- IT'S MORE THAN A DOLL." "IT'S A WORK OF ART." "Andrew:" "HI." "THERE YOU GO." "AM I DOING THIS RIGHT?" "YEP." "YOU'RE DOING GREAT." "JUST MAKE SURE YOU SUPPORT HIS HEAD." "OH, MY GOSH." "THIS IS AWESOME." "CAN YOU IMAGINE?" "THE " " THE DIAPER CHANGING, THE CRYING, THE LACK OF SLEEP." "I MEAN, THAT POOR GUY HAS NO IDEA WHAT HE'S IN FOR." "I DON'T KNOW." "IT WOULDN'T BE THAT BAD." "YOU TOO?" "HUH?" "[ SIGHS ]" "DONNIE WANTS TO HAVE A WHOLE LITTER OF KIDS." "HE'S ON A MISSION TO BUY A GIGANTIC HOUSE" "SO I CAN START POPPING THEM OUT NOW." "WOW." "I HAD NO IDEA YOU GUYS WERE..." "[ CHUCKLES ] CONGRATULATIONS." "WELL, IT'S JUST " "I'M NOT SURE I'M READY FOR KIDS JUST YET." "YOU'VE GOT TIME." "WHAT IF TIME WASN'T THE ISSUE?" "YOU AFRAID YOU WON'T BE ABLE TO..." "NO, IT ISN'T THAT." "IT'S..." "I THINK WHAT I'M GETTING AT IS..." "I DON'T THINK I WANT KIDS AT ALL." "DID YOU TELL DONNIE THIS?" "I'M JUST WORRIED ABOUT DISAPPOINTING HIM." "OR WORSE." "WELL, YOU'RE GONNA HAVE TO BE HONEST WITH HIM, KATE." "Kate:" "SO, UM, WE'RE GETTING MARRIED AGAIN." "AND YOU'RE SHOWING ME PHOTOS OF A BIG HOUSE IN THE 'BURBS," "AND YOU'RE TALKING ABOUT YARDS AND SCHOOL DISTRICTS." "I KNEW IT." "I KNEW IT." "I KNEW IT." "YOU DON'T WANT TO LIVE IN THE SUBURBS, DO YOU?" "YOU KNOW WHAT?" "FORGET THE HOUSE." "YOU'RE RIGHT." "IT'S WAY TOO BIG FOR US," "AND THE COMMUTE WOULD PROBABLY BE HELL ANYWAY." "WE'RE CITY PEOPLE." "I'LL START LOOKING FOR AN AWESOME THREE-BEDROOM HERE." "MAYBE SOMETHING NEAR THE PARK." "AND WE'LL TAKE OUR KIDS TO MUSEUMS" "AND DINNER AT FANCY RESTAURANTS." "I MEAN, CULTURE IS REALLY GOOD FOR KIDS, RIGHT?" "I LOVE YOU." "[ CHUCKLES ]" "[ SIGHS ]" "Daniel:" "HOW MANY OF YOU HAVE HEARD THE TERM "MOMMY BRAIN"?" "FOR GENERATIONS, WOMEN HAVE BEEN TOLD" "THAT HAVING CHILDREN WILL TURN THEIR BRAINS TO MUSH," "THAT THE DEMANDS OF MOTHERHOOD" "WILL CAUSE THEM TO SPIRAL INTO MINDLESS BEHAVIOR," "LIKE PUTTING THE KEYS IN THE REFRIGERATOR" "OR THE MILK IN THE CLOSET." "BUT IN FACT, RECENT STUDIES SHOW" "THAT NEW MOTHERS DEVELOP CERTAIN COGNITIVE ENHANCEMENTS." "THE HYPOTHALAMUS, THE AMYGDALA, AND THE PREFRONTAL CORTEX" "ACTUALLY GROW POSTPARTUM." "THESE AREAS MOTIVATE A MOM TO, UH " " TO CARE FOR HER INFANT," "TO ENJOY THE SIMPLE INTERACTIONS," "AND TO BE MORE EFFECTIVE" "AT SKILLS LIKE REASONING, PLANNING, AND JUDGMENT." "PUT ANOTHER WAY, LOVE GROWS A MOTHER'S BRAIN." "LITERALLY." "BUT WHAT ABOUT DADS?" "MEN'S TESTOSTERONE LEVELS DROP BY ABOUT A THIRD" "IN THE WEEKS FOLLOWING THEIR CHILD'S ARRIVAL," "MAKING THEM MORE NURTURING, LESS AGGRESSIVE." "BUT BEFORE YOU GUYS START PANICKING" "ABOUT THE OTHER SIDE EFFECT OF LOW "T,"" "JUST KEEP IN MIND THAT YOUR WIFE WILL PROBABLY" "BE MORE INTERESTED IN THE BABY THAN IN YOUR BABY MAKER." "[ LAUGHTER ]" "AS AMAZING AS THESE BRAIN MAKEOVERS ARE," "ALL THE NEUROBIOLOGY IN THE WORLD" "CAN'T EXPLAIN THE JOY THAT COMES FROM HOLDING A NEWBORN." "OR FROM WITNESSING THE MIRACLE OF NEW LIFE." "OR SO I'M TOLD."
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Q: Typescript style guide for interfaces this is a question that may not have a single correct answer, as I do realise coding styles are quite varied, especially between different languages, eg camel case function names in javascript vs pascal casing methods in C#. I can quite accept that. Maybe I am over worrying about this, but I am just starting to look into typescript, really like the looks of it and plan to use it along with Angular2, and want to establish a good style guide. What I really don't get is point 2 here, not to use I prefix for interfaces. Until this, I thought that was almost universal. I have a class Car, so a natural name if the interface is just to add an I in front... ICar. As soon as you see the I prefix you know you have an interface. I want to follow any suggested practice, but this one I really do not know which why to go. Does none know why, what I thought was an almost universal convention, is being discouraged here? I know you can use whatever conventions you like, just wondering if there is some reason for this common convention not to be used in Typescript. Thanks in advance for any opinions/info! A: I as prefix was big at some time for Java and C# (probably also others) but I don't think this is still considered a good idea but how can one change something that is used by the majority of developers and existing code base. It's similar to hungarian notation which is universally considered bad practice. Just give it a meaningful name. If you have different kinds of Cars than make Car the universal interface and class FancyCar implements Car is much more natural. Things like prefixes just prevent people from thinking about what they really want to express. See also http://c2.com/cgi/wiki?IntentionRevealingNames There are also languages like Dart (probably many others I don't know) where there is not such a clear distinction between interface and class. In Dart you can implement any class. The class' interface just acts as an interface. update I don't say naming is easy. In fact I think it's the most or at least among the most difficult parts of software development. It's just that the general consesus of "the elite" is that prefixes for technical reasons are not the best approach. This doesn't mean there are alternative that have only advantages and no drawbacks. It seems in this case naming like UserService, UserServiceImpl, MockUserService is used instead. This way in most parts of your code the most natural way UserService is used and the derivates only in prividers. Otherwise, as mentioned above, consistency is way more important. If some style is more common in the language you use, I suggest to use this in your code as well. A: Similar question is asked here Confused about the Interface and Class coding guidelines for TypeScript My answer on it: https://stackoverflow.com/a/41967120/586609 Reasons: The times of the Hungarian notation have passed I-prefix violates encapsulation principle Protection from bad naming Properly chosen names vaccinate you against API Design Myth: Interface as Contract.
{ "pile_set_name": "StackExchange" }
Common variants in RB1 gene and risk of invasive ovarian cancer. Somatic alteration of the RB1 gene is common in several types of cancer, and germ-line variants are implicated in others. We have used a single nucleotide polymorphism (SNP) tagging approach to evaluate the association between common variants (SNP) in RB1 and risks of invasive ovarian cancer. We genotyped 11 tagging SNPs in three ovarian case-control studies from the United Kingdom, United States, and Denmark, comprising >1500 cases and 4,800 controls. Two SNPs showed significant association with ovarian cancer risk: carriers of the minor allele of rs2854344 were at reduced risk compared with the common homozygotes [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.61-0.89; P = 0.0009 dominant model]. Similarly, the minor allele of rs4151620 was found to be associated with reduced risk (rare versus common homozygote; OR, 0.19; 95% CI, 0.07-0.53; P = 0.00005 recessive model). After adjusting for multiple testing, the most significant association (rs4151620) was P = 0.001. A global test comparing common haplotype frequencies in cases and controls was of borderline significance (P(8df) = 0.04). There are no common coding SNPs in the RB1 gene. However, intron 17 of RB1 contains the open reading frame for the P2RY5 gene, and rs4151620 is perfectly correlated with rs2227311, which is located in the 5'-untranslated region of P2RY5 and is predicted to affect P2RY5 transcription. rs2854344 has been reported previously to be associated with breast cancer risk. The possible associations of rs2854344 and rs4151620 with ovarian cancer risk warrant confirmation in independent case-control studies before studies on their biological mode of action.
{ "pile_set_name": "PubMed Abstracts" }
The data underlying the results presented in the study are available from the John Hopkins Coronavirus resource center. URL: <https://coronavirus.jhu.edu/map.html>. Introduction {#sec001} ============ The first reported case of the novel coronavirus (SARS-CoV-2) in South Africa was announced on 5 March 2020, following the initial manifestation of the virus in Wuhan China in December 2019 \[[@pone.0237126.ref001]--[@pone.0237126.ref003]\]. Due to its further spread and the severity of its associated clinical outcomes, the disease was subsequently declared a pandemic by the World Health Organisation (WHO) on 11 March 2020 \[[@pone.0237126.ref001], [@pone.0237126.ref002]\]. In South Africa, by 26 April 2020, 4546 people had been confirmed to have been infected by the coronavirus with 87 fatalities \[[@pone.0237126.ref004]\]. Numerous states have attempted to minimise the growth in number of COVID-19 infections \[[@pone.0237126.ref001], [@pone.0237126.ref005], [@pone.0237126.ref006]\]. These attempts are largely based on non-pharmaceutical interventions (NPIs) aimed at separating the infectious population from the susceptible population \[[@pone.0237126.ref001]\]. These initiatives aim to strategically reduce the increase in infections to a level where their healthcare systems stand a chance of minimising the number of fatalities \[[@pone.0237126.ref001]\]. Some of the critical indicators for policymaker response planning include projections of the infected population, estimates of health care service demand and whether current containment measures are effective \[[@pone.0237126.ref001]\]. As the pandemic develops in a rapid and varied manner in most countries, calibration of epidemiological models based on available data can prove to be \[[@pone.0237126.ref007]\]. This difficulty is further escalated by the high number of asymptomatic cases and the limited testing capacity \[[@pone.0237126.ref001], [@pone.0237126.ref002]\]. A fundamental issue when calibrating localised models is inferring parameters of compartmental models such as susceptible-infectious-recovered (SIR) and the susceptible-exposed-infectious-recovered (SEIR) that are widely used in infectious disease projections. In the view of public health policymakers, a critical aspect of projecting infections is the inference of parameters that align with the underlying trajectories in their jurisdictions. The spreading rate is a parameter of particular interest which is subject to changes due to voluntary social distancing measures and government-imposed contact bans. The uncertainty in utilising these models is compounded by the limited data in the initial phases and the rapidly changing dynamics due to rapid public policy changes. To address these complexities, we utilise the Bayesian Framework for the inference of epidemiological model parameters in South Africa. The Bayesian framework allows for both incorporation of prior knowledge and principled embedding of uncertainty in parameter estimation. In this work we combine Bayesian inference with the compartmental SEIR and SIR models to infer time varying spreading rates that allow for quantification of the impact of government interventions in South Africa. Methods {#sec002} ======= Epidemiological modelling {#sec003} ------------------------- Compartmental models are a class of models that is widely used in epidemiology to model transitions between various stages of disease \[[@pone.0237126.ref001], [@pone.0237126.ref008], [@pone.0237126.ref009]\]. We now introduce the Susceptible-Exposed-Infectious-Recovered (SEIR) and the related Susceptible-Infectious-Recovered (SIR) compartmental models that have been dominant in COVID-19 modelling literature \[[@pone.0237126.ref001], [@pone.0237126.ref005], [@pone.0237126.ref006], [@pone.0237126.ref010]\]. ### The Susceptible-Exposed-Infectious-Recovered Model {#sec004} The SEIR is an established epidemiological model for the projection of infectious diseases. The SEIR models the transition of individuals between four stages of a condition, namely: - being susceptible to the condition, - being infected and in incubation - having the condition and being infectious to others and - having recovered and built immunity for the disease. The SEIR can be interpreted as a four-state Markov chain which is illustrated diagrammatically in [Fig 1](#pone.0237126.g001){ref-type="fig"}. The SEIR relies on solving the system of ordinary differential equations below representing the analytic trajectory of the infectious disease \[[@pone.0237126.ref001]\]. $$\begin{array}{rc} \frac{dS}{dt} & {= - \frac{\lambda SI}{N}} \\ \end{array}$$ $$\begin{array}{rc} \frac{dE}{dt} & {= \frac{\lambda SI}{N} - \sigma E} \\ \end{array}$$ $$\begin{array}{rc} \frac{dI}{dt} & {= \sigma E - \mu I} \\ \end{array}$$ $$\begin{array}{rc} \frac{dR}{dt} & {= \mu I} \\ \end{array}$$ Where S is the susceptible population, I is the infected population, R is the recovered population and N is the total population where *N* = *S* + *E* + *I* + *R*. λ is the transmission rate, *σ* is the rate at which individuals in incubation become infectious, and *μ* is the recovery rate. 1/*σ* and 1/*μ* therefore, become the incubation period and contagious period respectively. ![An Illustration of the underlying states of the Susceptible-Exposed-Infectious-Recovered Model(SEIR).](pone.0237126.g001){#pone.0237126.g001} We also consider the Susceptible-Infectious-Recovered (SIR) model which is a subclass of the SEIR model that assumes direct transition from the susceptible compartment to the infected (and infectious) compartment. The SIR is represented by three coupled ordinary differential equations rather than the four in the SEIR. [Fig 2](#pone.0237126.g002){ref-type="fig"} depicts the three states of the SIR model. ![An Illustration of the underlying states of the Susceptible-Infectious-Recovered Model(SIR).](pone.0237126.g002){#pone.0237126.g002} ### The basic reproductive number *R*~0~ {#sec005} The basic reproductive number (*R*~0~) represents the mean number of additional infections created by one infectious individual in a susceptible population. According to the latest available literature, without accounting for any social distancing policies the *R*~0~ for COVID-19 is between 2 and 3.5 \[[@pone.0237126.ref002], [@pone.0237126.ref006], [@pone.0237126.ref010], [@pone.0237126.ref011]\]. *R*~0~ can be expressed in terms of λ and *μ* as: $$\begin{array}{r} {R_{0} = \frac{\lambda}{\mu}} \\ \end{array}$$ ### Extensions to the SEIR and SIR models {#sec006} We use an extended version of the SEIR and SIR models of \[[@pone.0237126.ref006]\] that incorporates some of the observed phenomena relating to COVID-19. First we include a delay *D* in becoming infected (*I*^new^) and being reported in the confirmed case statistics, such that the confirmed reported cases CR~*t*~ at some time *t* are in the form \[[@pone.0237126.ref006]\]: $$\begin{array}{r} {\text{CR}_{t} = I_{t - D}^{\text{new}}} \\ \end{array}$$ We further assume that the spreading rate λ is time-varying rather than constant with change points that are affected by government interventions and voluntary social distancing measures. Bayesian parameter inference {#sec007} ---------------------------- We follow the framework of \[[@pone.0237126.ref006]\] to perform Bayesian inference for model parameters on the South African COVID-19 data. The Bayesian framework allows for the posterior inference of parameters which updates prior beliefs based on a data-driven likelihood. The posterior inference is governed by Bayes theorem as follows: $$\begin{array}{r} {P\left( W \middle| D,M \right) = \frac{P\left( D \middle| W,M \right)P\left( W \right)}{P\left( D \right)}} \\ \end{array}$$ Where *P*(*W*\|*D*, *M*) is the posterior distribution of a vector of model parameters (*W*) given the model(M) and observed data(D), *P*(*D*\|*W*, *M*) is the data likelihood and *P*(*D*) is the evidence. ### The likelihood {#sec008} The Likelihood indicates the probability of observing the reported case data given the assumed model. In our study, we adopt the Student-T distribution as the Likelihood as suggested by \[[@pone.0237126.ref006]\]. Similar to a Gaussian likelihood, the Student-T likelihood allows for parameter updates that minimise discrepancies between the predicted and observed reported cases. ### Priors {#sec009} Parameter prior distributions encode some prior subject matter knowledge into parameter estimation. In the case of epidemiological model parameters, priors incorporate literature based expected values of parameters such as recovery rate(*μ*), spreading rate(λ), change points based on policy interventions etc. The prior settings for the model parameters are listed in [Table 1](#pone.0237126.t001){ref-type="table"}. We follow \[[@pone.0237126.ref006]\] by selecting LogNormal distributions for λ and *σ* such that the initial mean basic reproductive number is 3.2 which is consistent with literature \[[@pone.0237126.ref002], [@pone.0237126.ref005], [@pone.0237126.ref006], [@pone.0237126.ref010], [@pone.0237126.ref012]\]. We set a LogNormal prior for the *σ* such that the mean incubation period is five days. We use the history of government interventions to set priors on change points in the spreading rate. The priors on change-points include 19/03/2020 when a travel ban and school closures were announced, and 28/03/2020 when a national lockdown was enforced. We keep the priors for the Lognormal distributions of the spreading rates after the change points weakly-informative by setting the same mean as λ~0~ and higher variances across all change points. This has the effect of placing greater weight on the data driven likelihood. Similar to \[[@pone.0237126.ref006]\] we adopt weakly-informative Half-Cauchy priors for the initial conditions for the infected and exposed populations. 10.1371/journal.pone.0237126.t001 ###### Prior distribution settings for SEIR and SIR model parameters. ![](pone.0237126.t001){#pone.0237126.t001g} Parameter Prior Distribution ----------------------------------- ------------------------- Spreading rate λ~0~ LogNormal(log(0.4),0.5) Spreading rate λ~1~ LogNormal(log(0.4),0.7) Spreading rate λ~2~ LogNormal(log(0.4),0.7) Incubation to infectious rate *σ* LogNormal(log(1/5),0.5) Recovery rate *μ* LogNormal(log(1/8),0.2) Reporting Delay *D* LogNormal(log(8),0.2) Initial Infectious *I*~0~ Half-Cauchy(20) Initial Exposed *E*~0~ Half-Cauchy(20) Change Point *t*~1~ Normal(2020/03/18,1) Change Point *t*~2~ Normal(2020/03/28,1) ### Markov Chain Monte Carlo (MCMC) {#sec010} Given that the closed-form inference of the posterior distributions on the parameters listed in [Table 1](#pone.0237126.t001){ref-type="table"} is infeasible, we make use of Markov Chain Monte Carlo to sample from the posterior. Monte Carlo methods approximate solutions to complex numerical problems by simulating a random process. MCMC uses a Markov Chain to sample from the posterior distribution, where a Markov Chain is a sequence of random variables *W*~*t*~ such that: $$P\left( W_{t + 1} \middle| W_{1},...,W_{t} \right) = P\left( W_{t + 1} \middle| W_{t} \right)$$ MCMC techniques have been widely used in COVID-19 parameter inference \[[@pone.0237126.ref006], [@pone.0237126.ref010]\]. In this work, we explore inference using Metropolis-Hastings (MH), Slice Sampling and No-U-Turn Sampler (NUTS). ### Metropolis Hastings (MH) {#sec011} MH is one of the simplest algorithms for generating a Markov Chain which converges to the correct stationary distribution. The MH generates proposed samples using a proposal distribution. A new parameter state *W*~*t*\*~ is accepted or rejected probabilistically based on the posterior likelihood ratio: $$\begin{array}{r} {P\left( accept\left( W_{t*} \right) \right) = min\left( 1,\frac{P\left( W_{t*} \middle| D,M \right)}{P\left( W^{t - 1} \middle| D,M \right)} \right)} \\ \end{array}$$ A common proposal distribution is a symmetric random walk obtained by adding Gaussian noise to a previously accepted parameter state. Random walk behaviour of such a proposal typically results in low sample acceptance rates. ### Slice sampling {#sec012} Slice sampling facilitates sampling from the posterior distribution *P*(*W*\|*D*, *M*) by adding an auxiliary variable *u* such that the joint posterior distribution becomes: $$\begin{array}{r} {P\left( W,u \middle| D,M \right) = \left\{ \begin{array}{ll} \frac{1}{Z} & {\mspace{720mu}{0 \leq U \leq P\left( W \middle| D,M \right)}} \\ 0 & \text{Otherwise} \\ \end{array}\operatorname{} \right.} \\ \end{array}$$ Where *Z* = ∫*P*(*W*\|*D*, *M*)*dW* which is a normalisation constant. Marginal samples for the parameters W can then be obtained by ignoring *u* samples from the joint samples. This process corresponds to sampling above the slice of the posterior density function around a predefined window. [Fig 3](#pone.0237126.g003){ref-type="fig"} shows an illustration of slice sampling. ![An illustration of slice sampling, moving from a parameter sample w(i) to w(i + 1) via auxiliary variable sample u(i + 1).](pone.0237126.g003){#pone.0237126.g003} While sample acceptance is guaranteed with slice sampling, a large slice window can lead to computationally inefficient sampling while a small window can lead to poor mixing. ### Hybrid Monte Carlo (HMC) and the No-U-Turn Sampler (NUTS) {#sec013} Metropolis-Hastings (MH) and slice sampling tend to exhibit excessive random walk behaviour---where the next state of the Markov Chain is randomly proposed from a proposal distribution \[[@pone.0237126.ref013]--[@pone.0237126.ref015]\]. This results in low proposal acceptance rates and small effective sample sizes. HMC proposed by \[[@pone.0237126.ref016]\] reduces random walk behaviour by adding auxiliary momentum variables to the parameter space \[[@pone.0237126.ref015]\]. HMC creates a vector field around the current state using gradient information, which assigns the current state a trajectory towards a high probability next state \[[@pone.0237126.ref015]\]. The dynamical system formed by the model parameters *W* and the auxiliary momentum variables *p* is represented by the Hamiltonian *H*(*W*, *p*) written as follows \[[@pone.0237126.ref015], [@pone.0237126.ref016]\]: $$\begin{array}{r} {H\left( W,p \right) = M\left( W \right) + K\left( p \right)} \\ \end{array}$$ Where *M*(*W*) is the negative log-likelihood of the posterior distribution in [Eq 7](#pone.0237126.e007){ref-type="disp-formula"}, also referred to as the potential energy. *K*(*p*) is the kinetic energy defined by the kernel of a Gaussian with a covariance matrix *M* \[[@pone.0237126.ref017]\]: $$\begin{array}{r} {K\left( p \right) = \frac{p^{T}M^{- 1}p}{2}.} \\ \end{array}$$ The trajectory vector field is defined by considering the parameter space as a physical system that follows Hamiltonian Dynamics \[[@pone.0237126.ref015]\]. The dynamical equations governing the trajectory of the chain are then defined by Hamiltonian equations at a fictitious time *t* as follows \[[@pone.0237126.ref016]\]: $$\begin{array}{r} {\frac{\partial w_{i}}{\partial t} = \frac{\partial H}{\partial p_{i}}} \\ \end{array}$$ $$\begin{array}{r} {\frac{\partial p_{i}}{\partial t} = - \frac{\partial H}{\partial w_{i}}} \\ \end{array}$$ In practical terms, the dynamical trajectory is discretised using the leapfrog integrator. In the leapfrog integrator to reach the next point in the path, we take half a step in the momentum direction, followed by a full step in the direction of the model parameters---then ending with another half step in the momentum direction. Due to the discretising errors arising from leapfrog integration a Metropolis acceptance step is then performed in order to accept or reject the new sample proposed by the trajectory \[[@pone.0237126.ref015], [@pone.0237126.ref018]\]. In the Metropolis step the parameters proposed by the HMC trajectory *w*\* are accepted with the probability \[[@pone.0237126.ref016]\]: $$\begin{array}{r} {P\left( accept \right) = \min\left( 1,\frac{P\left( w^{*} \middle| D,\alpha,\beta,H \right)}{P\left( w \middle| D,\alpha,\beta,H \right)} \right)} \\ \end{array}$$ Algorithm 1 shows the pseudo-code for the HMC where *ϵ* is a discretisation stepsize. The leapfrog steps are repeated until the maximum trajectory length *L* is reached. **Algorithm 1**: Hybrid Monte Carlo Algorithm **Data**: Confirmed Cases dataset {**C**^(*t*)^} **Result**: *N* Samples of model parameters **W** **for** *n* ← 1 **to** *N* **do**  *w*~0~ ← *w*~init~  *sample the auxiliary momentum variables p*   $\text{p} \sim \mathcal{N}\left( 0,\mathbf{M} \right)$  Use leapfrog steps to generate proposals for *w*  **for** *t* ← 1 **to** *L* **do**    $$\left. p\left( t + \epsilon/2 \right)\leftarrow p\left( t \right) + \left( \epsilon/2 \right)\frac{\partial H}{\partial w}\left( w\left( t \right) \right) \right.$$    $$\left. w\left( t + \epsilon \right)\leftarrow w\left( t \right) + \epsilon\frac{p\left( t + \epsilon/2 \right)}{M} \right.$$    $$\left. p\left( t + \epsilon \right)\leftarrow p\left( t + \epsilon/2 \right) + \left( \epsilon/2 \right)\frac{\partial H}{\partial w}\left( w\left( t + \epsilon \right) \right) \right.$$  **end**  *Metropolis Update step*:  (*p*, *w*)~*n*~ ← (*p*(*L*), *w*(*L*)) with probability:   $$min\left( 1,\frac{P\left( w_{t*} \middle| D,M \right)}{P\left( w \middle| D,M \right)} \right)$$ **end** The HMC algorithm has multiple parameters that require tuning for efficient sampling, such as the step size and the trajectory length. In terms of trajectory length, a trajectory length that is too short leads to random walk behaviour similar to MH. While a trajectory length that is too long results in a trajectory that inefficiently traces back. The stepsize is also a critical parameter for sampling, small stepsizes are computationally inefficient leading to correlated samples and poor mixing while large stepsizes compound discretisation errors leading to low acceptance rates. Tuning these parameters requires multiple time consuming trial runs. NUTS automates the tuning of the leapfrog stepsize and trajectory length. In NUTS the stepsize is tuned during an initial burn-in phase by targeting particular levels of sample acceptance. The trajectory length is tuned by iteratively adding steps until either the chain starts to trace back (U-turn) or the Hamiltonian explodes (becomes infinite). We use the samplers described above to calibrate the SEIR and SIR models on daily new cases and cumulative cases data for South Africa up to and including 20 April 2020 provided by Johns Hopkins University's Center for Systems Science and Engineering(CSSE) \[[@pone.0237126.ref003]\]. Results {#sec014} ======= SIR and SEIR model parameter inference was performed using confirmed cases data up to and including 20 April 2020 and MCMC samplers described in the methodology section. Each of the samplers are run such that 5000 samples are drawn with 1000 burn-in and tuning steps. We use leave-one-out(LOO) cross-validation error of \[[@pone.0237126.ref019]\] to evaluate the goodness of fit of each model. [Table 2](#pone.0237126.t002){ref-type="table"} shows the LOO validation errors of the various models. It can be seen that the SIR model with two change points as the best model fit with the lowest mean LOO of 448.00. The SEIR model with two change points showed a mean LOO of 459.94. We note that \[[@pone.0237126.ref006]\] similarly finds that the SIR model displayed superior goodness of fit to the SEIR on German data. 10.1371/journal.pone.0237126.t002 ###### Leave-one out (LOO) statistics comparing SEIR and SIR models with different number of change points. ![](pone.0237126.t002){#pone.0237126.t002g} Model Change Points LOO Effective Parameters ------- --------------- -------- ---------------------- SIR 2 448.00 10.27 SEIR 1 457.77 11.60 SEIR 2 459.94 12.00 SIR 1 463.03 8.51 SEIR 0 464.69 16.14 SIR 0 517.72 4.72 We now further present detailed results of the SIR and SEIR models with inference using NUTS, the trace plots from these models indicating stationarity in the sampling chains are provided in [S2](#pone.0237126.s002){ref-type="supplementary-material"} and [S5](#pone.0237126.s005){ref-type="supplementary-material"} Figs. The trace plots for the SIR and SEIR models using MH are provided in [S3](#pone.0237126.s003){ref-type="supplementary-material"} and [S6](#pone.0237126.s006){ref-type="supplementary-material"} Figs, while similar trace plots for slice sampling are provided in [S4](#pone.0237126.s004){ref-type="supplementary-material"} and [S7](#pone.0237126.s007){ref-type="supplementary-material"} Figs. The trace plots largely indicate that the NUTS sampler displays greater agreement between parallel chains thus lower rhat values. Posterior parameter distributions {#sec015} --------------------------------- [Fig 4](#pone.0237126.g004){ref-type="fig"} shows the posterior distributions of the SIR model parameters. The parameter estimates are λ~0~ ≈ 0.495 (CI\[0.41, 0.564\]), λ~1~ ≈ 0.099 (CI\[0.065, 0.145\]), λ~2~ ≈ 0.197 (CI\[0.134, 0.264\]), *μ* ≈ 0.151 (CI\[0.09, 0.205\]) and reporting delay (*D*) ≈ 6.848 (CI\[5.178, 8.165\]). This corresponds to *R*~0~ values of 3.278 (CI\[2.715, 3.73\]), 0.655 (CI\[0.430, 0.960\]) and 1.304 (CI\[0.887, 1.7748\]) at the respective change points. [S1 Fig](#pone.0237126.s001){ref-type="supplementary-material"} further shows the joint posterior distributions of λ~*t*~ and *μ* at each of the change points. ![Posterior parameter distributions for the SIR model with two change points.](pone.0237126.g004){#pone.0237126.g004} Time-varying spread rates allow for inference of the impact of various state and societal interventions on the spreading rate. [Fig 5](#pone.0237126.g005){ref-type="fig"} shows the fit and projections based on SIR models with zero, one and two change points. As can be seen from the plot the two change point model best captures the trajectory in the development of new cases relative to the zero and one change point models. The superior goodness of fit of the two change point model is also illustrated in [Table 2](#pone.0237126.t002){ref-type="table"}. The fit and projections showing similar behaviour on the SEIR model with various change points are shown in [Fig 6](#pone.0237126.g006){ref-type="fig"}. ![Predictions and actual data(until 20 April 2020) based on SIR models with various change points.\ The top plot indicates the actual and projected new cases while the bottom plot shows the actual and projected cumulative cases.](pone.0237126.g005){#pone.0237126.g005} ![Predictions and actual data(until 20 April 2020) based on SEIR models with various change points.\ The top plot indicates the actual and projected new cases while the bottom plot shows the actual and projected cumulative cases.](pone.0237126.g006){#pone.0237126.g006} Reporting delays, incubation and infectious period {#sec016} -------------------------------------------------- The mean reporting delay time in days was found to be 6.848 (CI\[5.178, 8.165\]), literature suggests this delay includes both the incubation period and the test reporting lags. The posterior distribution incubation period from the SEIR model in [Fig 7](#pone.0237126.g007){ref-type="fig"} yields a median incubation period of 4.537 days (CI\[2.499, 6.787\]). Thus suggesting a mean laboratory reporting delay of approximately 2.311 days. A mean recovery rate *μ* ≈ 0.151 implies mean infectious period of 6.620 days which is in line with related literature \[[@pone.0237126.ref002], [@pone.0237126.ref006], [@pone.0237126.ref010]\]. ![Posterior parameter distributions under SEIR model with two change points.](pone.0237126.g007){#pone.0237126.g007} Timing and impact of interventions {#sec017} ---------------------------------- [Fig 8](#pone.0237126.g008){ref-type="fig"} depicts the posterior distributions of the spreading rates and times corresponding to each change point. We observe that the first change point is on a mean date of 18 March 2020 (CI:\[16/03/2020, 20/03/2020\]). This date is consistent with the travel ban, school closures and social distancing recommendations. This change point resulted in a substantial decrease in the spreading rate (80%) primarily due to the reduction in imported infections. ![Posterior distributions of the spreading rates(λ~*t*~) and the corresponding distributions of the time points.](pone.0237126.g008){#pone.0237126.g008} The second change point is observed on 28 March 2020 (CI:\[26/03/2020, 30/03/2020\]). This time point coincides with the announcement of mass screening and testing by the government on 30 March 2020. The resulting mean *R*~0~ of 1.304 implies a 60% decrease from the initial value. The inference of parameters is dependent on the underlying testing processes that generate the confirmed case data. The effect of the mass screening and testing campaign was to change the underlying confirmed case data generating process by widening the criteria of those eligible for testing. While initial testing focused on individuals that either had exposure to known cases or travelled to known COVID-19 affected countries, mass screening and testing further introduced detection of community level transmissions which may contain undocumented contact and exposure to COVID-19 positive individuals. Discussion {#sec018} ========== We have performed Bayesian parameter inference of the SIR and SEIR models using MCMC and publicly available data as at 20 April 2020. The resulting parameter estimates fall in-line with the existing literature in-terms of mean baseline *R*~0~ (before government action), mean incubation time and mean infectious period \[[@pone.0237126.ref002], [@pone.0237126.ref005], [@pone.0237126.ref006], [@pone.0237126.ref010]\]. We find that initial government action that mainly included a travel ban, school closures and stay-home orders resulted in a mean decline of 80% in the spreading rate. Further government action through mass screening and testing campaigns resulted in a second trajectory change point. This latter change point is mainly driven by the widening of the population eligible for testing, from travellers (and their known contacts) to include the generalised community who would have probably not afforded private lab testing which dominated the initial data. This resulted in an increase of *R*~0~ to 1.304. The effect of mass screening and testing can also be seen in [Fig 9](#pone.0237126.g009){ref-type="fig"} indicating a mean increase in daily tests preformed from 1639 to 4374. ![Daily COVID-19 tests performed in South Africa.\ The orange line indicates the segmented mean number of tests per day before and after the 28 March 2020 change point.](pone.0237126.g009){#pone.0237126.g009} The second change point illustrates the possible existence of multiple pandemics, as suggested by \[[@pone.0237126.ref020]\]. Thus testing after 28 March is more indicative of community-level transmissions that were possibly not as well documented in-terms of contact tracing and isolation relative to the initial imported infection driven pandemic. This is also supported by the documented increase in public laboratory testing (relative to private) past this change point, suggesting health care access might also play a role in the detection of community-level infections \[[@pone.0237126.ref021]\]. Conclusion {#sec019} ========== We have utilised a Bayesian inference framework to infer time-varying spreading rates of COVID-19 in South Africa. The time-varying spreading rates allow us to estimate the effects of government actions on the dynamics of the pandemic. The results indicate a decrease in the mean spreading rate of 60%, which mainly coincides with the containment of imported infections, school closures and stay at home orders. The results also indicate the emergence of community-level infections which are increasingly being highlighted by the mass screening and testing campaign. The development of the community level transmissions (*R*~0~ ≈ 1.3041 (CI\[0.887, 1.7748\])) of the pandemic at the time of publication appears to be slower than that of the initial traveller based pandemic (*R*~0~ ≈ 3.278 (CI\[2.715, 3.73\])). A future improvement to this work could include extensions to regional and provincial studies as current data suggests varied spreading rates both regionally and provincially. As more government interventions come to play priors on more change points might also be necessary. Supporting information {#sec020} ====================== ###### Two dimensional heat maps of the joint posterior distributions of the spreading rate(λ) and the recovery rate(*μ*) at various change points of the SIR model. The high joint density areas (in yellow) indicate likely values of *R*~0~. The baseline mean *R*~0~ estimate in S1 Fig (a) is 3.278, the first change point estimate in Fig S1 Fig (b) is 0.655 while the second change point in S1 Fig (c) has resulted in a mean *R*~0~ estimate of 1.304. (TIFF) ###### Click here for additional data file. ###### Shows diagnostic trace plots for the SIR model inferred using NUTS. (TIFF) ###### Click here for additional data file. ###### Shows diagnostic trace plots for the SIR model inferred using MH. (TIFF) ###### Click here for additional data file. ###### Shows diagnostic trace plots for the SIR model inferred using slice sampling. (TIFF) ###### Click here for additional data file. ###### Shows diagnostic trace plots for the SEIR model inferred using NUTS. (TIFF) ###### Click here for additional data file. ###### Shows diagnostic trace plots for the SEIR model inferred using MH. (TIFF) ###### Click here for additional data file. ###### Shows diagnostic trace plots for the SEIR model inferred using slice sampling. (TIFF) ###### Click here for additional data file. 10.1371/journal.pone.0237126.r001 Decision Letter 0 Shaman Jeffrey Academic Editor © 2020 Jeffrey Shaman 2020 Jeffrey Shaman This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 11 Jun 2020 PONE-D-20-12397 Bayesian Inference of COVID-19 Spreading Rates in South Africa PLOS ONE Dear Dr. Mbuvha, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE's publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please respond to the reviewer comments on a point-by-point basis and revise the manuscript accordingly. 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The PLOS ONE style templates can be found at <https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf> and <https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf> 2.We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: \- arXiv:1906.06382v1 \-<https://www.medrxiv.org/content/10.1101/2020.04.07.20057133v2> In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. Please also ensure you have described the source of your data in the methods section, including a link or citation which can be used to access the data. 3\. Please ensure that you refer to Figures 10,11 & 12 in your text as, if accepted, production will need this reference to link the reader to the figure. 4\. Please upload a copy of Supporting Information Appendix S1 which you refer to in your text on page 11. \[Note: HTML markup is below. Please do not edit.\] Reviewers\' comments: Reviewer\'s Responses to Questions **Comments to the Author** 1\. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer \#1: Yes \*\*\*\*\*\*\*\*\*\* 2\. Has the statistical analysis been performed appropriately and rigorously? Reviewer \#1: Yes \*\*\*\*\*\*\*\*\*\* 3\. Have the authors made all data underlying the findings in their manuscript fully available? The [PLOS Data policy](http://www.plosone.org/static/policies.action#sharing) requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data---e.g. participant privacy or use of data from a third party---those must be specified. Reviewer \#1: Yes \*\*\*\*\*\*\*\*\*\* 4\. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer \#1: Yes \*\*\*\*\*\*\*\*\*\* 5\. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer \#1: In their paper the authors analyse with Bayesian methods the increase of COVID-19 case numbers in South Africa. They find two change points in the propagation that they link to respectively to travel bans/containment of infections and onset of massive testing. They conclude that the governmental interventions linked to the first change point were effective. I recommend this paper for publication because of its timeliness and well described methods and would suggest a few minor revisions: \- In table 2 the authors list compare different sampling methods by their LOO statistic. As far as I understand it this is not useful and misleading. The LOO statistic was developed to compare different models (which are also correctly shown in this table). The lower LOO statistic of the MH sampling probably arises from a incomplete sampling of the posterior which could potentially be fixed letting the chains run longer and/or with a longer burn-in period. A useful statistic to check convergence is the Rhat statistic (<https://docs.pymc.io/api/stats.html#pymc3.stats.rhat>). \- The scale of the lambda_2 prior in the table 1 doesn\'t seem to match the prior distribution plotted in Fig. 4. The authors could also think about whether the lambda 1 and 2 priors are well motivated, and eventually make them wider/more uninformative. The posterior of the Lambda 1 prior is in the tail of the prior distribution (Fig. 4). \- In the algorithm of the HMC, in the third line of the leapfrog loop, the closing bracket after \"p(t\" should be removed. \*\*\*\*\*\*\*\*\*\* 6\. PLOS authors have the option to publish the peer review history of their article ([what does this mean?](https://journals.plos.org/plosone/s/editorial-and-peer-review-process#loc-peer-review-history)). If published, this will include your full peer review and any attached files. If you choose "no", your identity will remain anonymous but your review may still be made public. **Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our [Privacy Policy](https://www.plos.org/privacy-policy). Reviewer \#1: Yes: Jonas Dehning \[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link \"View Attachments\". If this link does not appear, there are no attachment files.\] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, <https://pacev2.apexcovantage.com/>. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at <[email protected]>. Please note that Supporting Information files do not need this step. 10.1371/journal.pone.0237126.r002 Author response to Decision Letter 0 7 Jul 2020 Dear Editor Kindly find our responses to reviews below. Best, Rendani Mbuvha \-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-- Responses to Academic Editor 1\. Please ensure that your manuscript meets PLOS ONE\'s style requirements, including those for file naming. The PLOS ONE style templates can be found at <https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf> and <https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf> Response We have made changes in line with the formatting guidelines, including: Changing the affiliation of one author from \'office of the vice-chancellor(his office)\' to the institute that he is affiliated to at the university Changing \'figure\' references to \'fig\' Moving supporting information to an appropriately named appendix Changing subsection headings accordingly 2.We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: \- arXiv:1906.06382v1 \-<https://www.medrxiv.org/content/10.1101/2020.04.07.20057133v2> In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. Response: We have made changes in terms of rewriting, rephrasing(with referencing) and inserting quotations in areas where there was previous overlapping text with our earlier preprints outside the methods section. Please see highlighted changes. Please also ensure you have described the source of your data in the methods section, including a link or citation which can be used to access the data. Response: We have added a description of our data source, including the necessary citation. 3\. Please ensure that you refer to Figures 10,11 & 12 in your text as, if accepted, production will need this reference to link the reader to the figure. Response: These figures have now been moved to the supporting information files with the relevant references included in the main text. 4\. Please upload a copy of Supporting Information Appendix S1 which you refer to in your text on page 11. Response: Now included as separate files - ( this mainly consists of the previous 'figures' 10-12 and other diagnostic plots) \-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-- Responses to Reviewer 1 I recommend this paper for publication because of its timeliness and well described methods and would suggest a few minor revisions: \- In table 2 the authors list compare different sampling methods by their LOO statistic. As far as I understand it this is not useful and misleading. The LOO statistic was developed to compare different models (which are also correctly shown in this table). The lower LOO statistic of the MH sampling probably arises from a incomplete sampling of the posterior which could potentially be fixed letting the chains run longer and/or with a longer burn-in period. A useful statistic to check convergence is the Rhat statistic (<https://docs.pymc.io/api/stats.html#pymc3.stats.rhat>). Response: We agree with the reviewer. We have revised table 2 to only refer to the comparison between models rather than include samplers. We have also increased the number of chain runs to 5000 and increased burn-in to 1000 runs with ten concurrent chains rather than four to increase the likelihood of convergence. \- The scale of the lambda_2 prior in the table 1 doesn\'t seem to match the prior distribution plotted in Fig. 4. The authors could also think about whether the lambda 1 and 2 priors are well motivated, and eventually make them wider/more uninformative. The posterior of the Lambda 1 prior is in the tail of the prior distribution (Fig. 4). Response: We have now changed both priors for lambda 1 and lambda 2 to a wider and relatively less informative LogNormal(log(0.4),0.7). The change in priors and running the chains for longer marginally changes mean estimates of posterior parameters \-- this does not seem to change the overall findings in a material way. \- In the algorithm of the HMC, in the third line of the leapfrog loop, the closing bracket after \"p(t\" should be removed. Response: We have amended the formula typo accordingly. ###### Submitted filename: Response to Reviewers.pdf ###### Click here for additional data file. 10.1371/journal.pone.0237126.r003 Decision Letter 1 Shaman Jeffrey Academic Editor © 2020 Jeffrey Shaman 2020 Jeffrey Shaman This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 22 Jul 2020 Bayesian Inference of COVID-19 Spreading Rates in South Africa PONE-D-20-12397R1 Dear Dr. Mbuvha, We're pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you'll receive an e-mail detailing the required amendments. 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For more information, please contact <[email protected]>. Kind regards, Jeffrey Shaman Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers\' comments: Reviewer\'s Responses to Questions **Comments to the Author** 1\. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the "Comments to the Author" section, enter your conflict of interest statement in the "Confidential to Editor" section, and submit your \"Accept\" recommendation. Reviewer \#1: All comments have been addressed \*\*\*\*\*\*\*\*\*\* 2\. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer \#1: Yes \*\*\*\*\*\*\*\*\*\* 3\. Has the statistical analysis been performed appropriately and rigorously? Reviewer \#1: Yes \*\*\*\*\*\*\*\*\*\* 4\. Have the authors made all data underlying the findings in their manuscript fully available? The [PLOS Data policy](http://www.plosone.org/static/policies.action#sharing) requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data---e.g. participant privacy or use of data from a third party---those must be specified. Reviewer \#1: Yes \*\*\*\*\*\*\*\*\*\* 5\. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer \#1: Yes \*\*\*\*\*\*\*\*\*\* 6\. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer \#1: The concerns have been fully addressed and in my opinion the manuscript is now acceptable for publication. \*\*\*\*\*\*\*\*\*\* 7\. PLOS authors have the option to publish the peer review history of their article ([what does this mean?](https://journals.plos.org/plosone/s/editorial-and-peer-review-process#loc-peer-review-history)). If published, this will include your full peer review and any attached files. If you choose "no", your identity will remain anonymous but your review may still be made public. **Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our [Privacy Policy](https://www.plos.org/privacy-policy). Reviewer \#1: **Yes: **Jonas Dehning [^1]: **Competing Interests:**The authors have declared that no competing interests exist.
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latest news Meaning Of Iowa Straw Poll Is That There Isn't One August 13, 2011 8:00 PM ET Frank James What was the meaning of the Ames Straw Poll in Iowa Saturday? In terms of the big picture, essentially nothing. The presumptive frontrunner for the Republican presidential nomination and winner of the 2007 straw poll, Mitt Romney, didn't even compete. Meanwhile, Texas Gov. Rick Perry, who entered the race Saturday and had polling numbers near Romney's even before entering the race, also didn't compete in the straw poll. That doesn't mean that the win won't help to further energize Rep. Michele Bachmann who came in first. But her charisma, her fundamentalist Christianity, her Iowa connection (she spent part of her early life there) and being from neighboring Minnesota all conspired to give her certain advantages with the social conservatives who powered her to victory. So she was expected to do well and did. It's still difficult to see how she gets past Romney and Perry to the nomination. The Iowa caucuses in February will be a different matter since, presumably, Romney and Perry will make a full push to win that contest. Also, while the Ames Straw Poll has occasionally aligned with the eventual winner of the nomination, it hasn't always. George H.W. Bush won it in 1979 but Ronald Reagan won the nomination. Preacher Pat Robertson won it it 1987 and also didn't win the nomination. Same for Romney in 2007. So it's definitely not a reliable predictor. The Latest On Pawlenty's Campaign The straw poll results actually did likely have serious consequences for Tim Pawlenty. The former Minnesota governor reportedly spent big to make a statement in the straw poll, about $1 million according to some reports. Despite all that, he still came in behind Paul and not by a little. He's also been far back in national polls. With Perry now in the race with his strong appeal to fiscal and social conservatives as well as Tea Party voters, Pawlenty will likely find himself even further back in the pack. It leaves Pawlenty in a difficult spot, having to ask himself just how much further he can go. Money-raising is likely to be an even bigger problem now for him. Pawlenty's campaign issued a message congratulating Bachmann and saying his campaign was headed to the next phase, including visits to New Hampshire and South Carolina, early primary states: "I need your support to continue the journey," was his message to voters. It was a brave message. But presidential nominations aren't won on courage alone. It takes money and a credible path to victory and Saturday's Iowa results hurt him in reaching either of those two goals.
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Det statliga forskningsbolaget VTT i Finland har börjat utveckla en liten kärnreaktor som ska ge fjärrvärme. Syftet är att skapa en ny inhemsk industri kring tekniken. Den finska fjärrvärmen produceras i dag från flera olika källor. Ungefär hälften kommer från koldioxidneutrala källor, det vill säga biomassa (42 procent) och värmeåtervinning (10 procent). Den andra halvan produceras av kol (18 procent), torv (14 procent), naturgas (11 procent) och en mindre del olja (2 procent). Enligt forskningsbolaget VTT gav den finska fjärrvärmen upphov till över fyra miljoner ton i koldioxidutsläpp förra året. I många städer blir värmeproduktionen en av de största klimatutmaningarna eftersom Finland har bestämt sig för att sluta använda kol 2029. – Tidplanen är utmanande och det finns få billiga alternativ. För att åstadkomma detta behövs nya innovationer och introduktion av ny teknik. Kärnkraft som ger fjärrvärme kan åstadkomma riktigt stora utsläppsminskningar, säger Ville Tulkki, forskningschef på VTT, i ett pressmeddelande. Värma vatten till 100 grader Celsius Men reaktorkonceptet behöver inte vara färdigt och förverkligat till kolförbudet 2029, anser han. Även efter det årtalet kommer fjärrvärmen att använda sig av många andra bränslen som kan ersättas av kärnkraft. – Vi försöker så klart se om vi kan hinna till 2029. Men om du frågar när vi kan ha en anläggning i drift så kan det bli när som helst mellan 2029 och 2035, säger Ville Tulkki till Ny Teknik. Koncept för små och modulära kärnreaktorer utvecklas världen över som ett svar på kostsamma förseningar i byggen av nya stora kärnkraftverk. Tanken är att små reaktorer ska kunna tillverkas snabbt och billigt i fabrik och transporteras i moduler till rätt plats, där de monteras. Enligt VTT avser de flesta av dessa koncept reaktorer som ska producera el eller värme med hög temperatur för olika industriprocesser. VTT:s plan är i stället att fokusera på en reaktor som kan värma vatten till ungefär 100 grader Celsius för fjärrvärme. Då blir det möjligt att nå ännu enklare och billigare lösningar, menar forskningsföretaget. "Trycksättning i nivå med däcken på en buss" Just nu tänker sig VTT att det blir en tryckvattenreaktor som antingen placeras i en 25 meter djup vattenbassäng eller i en reaktortank ovan eller under mark. Oavsett vilket spår som bolaget väljer är en reaktor för fjärrvärme betydligt enklare än en som ska ge el, enligt Ville Tulkki. – Vid elproduktion vill man ha högsta möjliga temperatur på ångan som driver turbinerna. Temperaturen är runt 350 grader Celsius och trycket blir runt 15 megapascal. För fjärrvärme behöver man en del trycksättning, men inte så mycket som 15 megapascals, mer i nivå med vad däcken på en buss har. Och väggarna i ett vanligt kärnkraftverk måste vara 20-25 centimeter tjocka men för fjärrvärme behöver de bara vara omkring en centimeter, säger Ville Tulkki. Genom att använda kärnkraft för att producera fjärrvärme behöver inte biomassa eldas upp för att ge värme. Det är en fördel, påtalar VTT, eftersom biomassa i framtiden kan bli en värdefull råvara som till exempel kan ersätta olja i industrin eller användas för att framställa transportbränslen. Kärnkraftverk i Schweiz värmer bostäder I dag är det relativt ovanligt att kärnkraftverk producerar fjärrvärme. Men Sveriges första kommersiella kärnkraftverk, som drevs på 1960- och 1970-talen i Ågesta söder om Stockholm, levererade faktiskt både fjärrvärme och el. Det var en liten reaktor som kunde ge som mest 68 MW fjärrvärme och 12 MW el. Ågesta kärnkraftverk drevs under 1960- och 1970-talen. Här syns kontrollrummet. Foto: Lennart Ström I Östeuropa är det dock betydligt vanligare att kärnkraftverk levererar både fjärrvärme och el. Ryssland har till exempel flera sådana kärnkraftverk. Även i Schweiz nyttjas kärnkraftverket Beznau för att värma omkring 2 400 bostäder. VTT:s reaktorkoncept ska tas fram genom avancerad modellering som blivit möjlig tack vare utvecklingen av processorkraft och parallellberäkningar. Målet med projektet är att skapa en ny industri runt tekniken där merparten av komponenterna kan tillverkas i Finland. Kärnenergilagen ses över Omkring 200 forskare på VTT ägnar sig åt kärnkraft. Under de senaste fem åren har företaget drivit flera projekt som rör små reaktorer. På Europanivå koordinerar VTT projektet Elsmor, som handlar om tillståndsprocesser för små modulära reaktorer. Dagens regelverk för kärnkraft är anpassat för stora anläggningar som ligger långt ifrån städerna. Men i Finland lanserades nyligen ett arbete för att göra om kärnenergilagen så att den bättre lämpar sig för prövning av små kärnkraftverk. Den finska strålskyddsmyndigheten, Stuk, förbereder också prövning av sådana reaktorer, rapporterar World Nuclear News.
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Comparison of BTA stat and NMP22 tests in the detection of bladder cancer. This study aimed to compare the BTA (bladder tumour antigen) stat and urinary nuclear matrix protein (NMP22) tests in the detection of bladder cancer. The office-based qualitative BTA stat and the laboratory-based quantitative NMP22 tests were studied in the same urine samples obtained from 49 patients with a high suspicion of bladder cancer and 20 healthy subjects. A tumour was identified in 36 patients after the cystoscopy. BTA stat demonstrated a sensitivity of 89%, which was superior to the sensitivity of 66.6% with the NMP22 test in detecting the bladder cancer (p < 0.02). The sensitivities for grade I tumours with BTA stat and NMP22 were 55.5% and 33.3%, respectively. The sensitivity of BTA stat was 100% for tumour categories except for the pTa and grade I tumours. No positive result was observed with both tests among the healthy subjects. The specificities for BTA stat and NMP22 were 78.7% and 69.6%, respectively. The BTA stat test was significantly more sensitive than the NMP22 test in the detection of bladder cancer. Although the sensitivity of BTA stat was not sufficient to replace cystoscopy, its ease and low cost may play a role in reducing the number of control cystoscopies, especially in patients with low risk of progression.
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Tissue fusion, a new opportunity for sutureless bypass surgery. Microsurgical suturing is the standard for cerebral bypass surgery, a technique where temporary occlusion is usually necessary. Non-occlusive techniques such as excimer laser-assisted non-occlusive anastomosis (ELANA) have certainly widened the spectrum of treatment of complex cerebrovascular situations, such as giant cerebral aneurysms, that were otherwise non-treatable. Nevertheless, the reduction of surgical risks while widening the spectrum of indications, such as a prophylactic cerebral bypass, is still a main aim, that we would like to pursue with our sutureless tissue fusion research. The primary concern in sutureless tissue fusion- and especially in tissue fusion of cerebral vessels- is the lack of reproducibility, often caused by variations in the thermal damage of the vessel. This has prevented this novel fusion technique from being applicable in daily surgical use. In this overview, we present three ways to further improve the laser tissue soldering technique.In the first section entitled "Laser Tissue Soldering Using a Biodegradable Polymer," a porous polymer scaffold doped with albumin (BSA) and indocyanine green (ICG) is presented, leading to strong and reproducible tensile strengths in tissue soldering. Histologies and future developments are discussed.In the section "Numerical Simulation for Improvement of Laser Tissue Soldering," a powerful theoretical simulation model is used to calculate temperature distribution during soldering. The goal of this research is to have a tool in hand that allows us to determine laser irradiation parameters that guarantee strong vessel fusion without thermally damaging the inner structures such as the intima and endothelium.In a third section, "Nanoparticles in Laser Tissue Soldering," we demonstrate that nanoparticles can be used to produce a stable and well-defined spatial absorption profile in the scaffold, which is an important step towards increasing the reproducibility. The risks of implanting nanoparticles into a biodegradable scaffold are discussed.Step by step, these developments in sutureless tissue fusion have improved the tensile strength and the reproducibility, and are constantly evolving towards a clinically applicable anastomosis technique.
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Hydraulically actuated boat hoists are shown in U.S. Pat. No. 6,823,809 to Hey, U.S. Pat. No. 6,976,442 to Hey U.S. Pat. No. 7,246,970 to Hey, U.S. Pat. No. 7,413,378 to Way and U.S. Pat. No. 8,267,621 to Way, all of which are incorporated herein by reference in their entirety. Southern U.S. States and coastal regions commonly use one of these three methods to store/moor boats: (1) Moor the boat to a fixed or floating pier using ropes. In this case, the boat remains in the water, (2) lift the boat using a platform or sling type lift mounted to a set of pilings or roof structure mounted on pilings, or (3) lift the boat using a floating lift system. The most common method used depends on the region and regulations governing the body of water. Many reservoirs do not allow private ownership of waterfront property. In these lakes, there tends to be large marinas or “dockominum” structures. In these structures in-water mooring is the most common. A small percentage of the boats are lifted using a floating lift. Floating lifts are usually the only type allowed on a large dock structure. Marina managers discourage any structure being fixed to these floating systems. Many lakes and waterways allow private waterfront ownership. In these cases, a permanent, fixed pier can be installed. Often a permanent roof structure is built over the slip intended for the boat commonly called a “boat house”. When these structures are present, a large percentage will have a mounted lift system. Some permanent docks do not have a roof structure. A lift is usually mounted on the top of large pilings when no roof is present. Pile and roof mounted lift systems have been around for decades. The lift designs are basically the same. Galvanized poles are mounted in bearings hanging from a beam in the roof or a beam mounted along the pilings. A “plate-gear” motor is connected to the end of the pole that causes the entire pole to turn. Cables are attached to the pole and wind as the pole turns. In lower capacity, roof-mount applications, one pole can be used, but in pile mount applications and higher capacity roof-mounts, two poles and motors are used. Some differentiation exists in the pole winding products. Some have improved on the motor and controls to included wireless operation. Some have added machined cable grooves to improve cable winding. There is even one company that uses a “level cable” technique to make a single motor/pole piling application. They also have some variation on the platform, bunks, and load guide features. Low-cost kits use a sling instead of a platform. Pole-winders have many weaknesses that present opportunities. Cable fatigue, motor synchronization, slow speed, poor corrosion resistance, and power supply issues are a short list of issues with current products. Cable fatigue is in a guaranteed failure mode if cables are not replaced every 2-3 years, depending on frequency of use. All of the designs on the market use wire rope. The galvanized poles used in these designs cause rapid fatigue of the cables because of the small winding diameter. Compounding the issue is the large lift height requirement for most installations. It is common to lift the boat 6-10′ to accommodate the fluctuating water heights. This requires many winds on the pole and in most cases, the cable winds over itself. This not only fatigues the cable, but also damages the individual wires with the wire rope. Cable failure modes are severe and cause the boat to fall in one direction endangering people and equipment. The most common approach to avoiding this failure is to replace cables often. Motor synchronization is also an issue in multi-pole/motor setups. Piling mount systems have at least two motors because there is no overhead structure to route cables to a single pipe. The speed of the motors will vary causing one to lift faster or slower than the other. Most systems require the user to use a switch to momentarily shut off one of the motors to allow the slower motor(s) to catch up. This requires constant user attention when lifting or lowering the boat. Compounding this issue is the slow speed of the pole winding systems. Some lifts can take over 6 minutes to lift the boat to the needed elevation above the water. The galvanized construction of the pole winding systems is adequate for most environments, but they eventually rust as the wound areas of the poles lose their zinc coating. The bearing locations are generally welded components. Aluminum or other naturally corrosion resistant materials are avoided because of the high stresses in these areas. Cable materials are often galvanized also due to the high replacement rate. The cable will be replaced due to fatigue before corrosion becomes an issue. Pole-winding systems are predominately A/C power systems. Piling mount systems require a long supply from the dock to the opposite motor. This can often be a 40-50′ length of cord to run down from the dock, tinder the water, and back up to the opposite motor. This length is too long for a DC (12-24V) power supply to run without extremely heavy wire. The length of the circuit from the supplying A/C panel to the motors is also very long. This often creates a large voltage drop along the circuit. The voltage drop can cause the system to malfunction and reduce the life of the motor(s) in the system. Often new installations require new circuits to be installed with heavier cable. A/C power can be dangerous system in wet environments. GFCI (ground fault circuit interrupts) are and absolute requirement on docks. Many lives have been lost due to damaged A/C circuits causing stray A/C currents in lakes and waterfronts with inadequate circuit protection. Pole winding systems are commonly used primarily because they can be easily installed in most existing structures with little modification and they are inexpensive when compared to floating or free-standing lift designs. The vast majority of floating lift systems are called “Air Displacement” systems. Air displacement systems raise and lower a lift structure using floats. The floats are filled with air that is evacuated to allow the structure to sink. The floats are then filled using vacuum pumps to raise the structure with the boat on it. Floating systems such as U.S. Pat. No. 6,823,809 to Hey have a few advantages over free standing and mounted lift structures. They can be used in very deep water where pile mounted systems are not an option. They can also be used in dockominium structures where a very limited structural connection is available. U.S. Pat. No. 6,823,809 to Hey shows a boat lift that mechanically lifts the boat using a unique linkage to lift the boat without requiring air evacuation. This hydraulic system is innovative, but expensive. The system also places critical hydraulic components at the waterline. This jeopardizes the durability of the system. Those boat hoists do not require any structural connection to the pier and can be moored similarly to the boat. But air displacement lifts require a mounted structure on the dock. As air is evacuated from the floats gravity will cause the structured to sink to the lakebed unless a structure is in place to limit the travel. This lift style does not work well in shallow areas because of the size of the floating structure. Lift capacity of floating lift systems is determined by the amount of flotation. The float structure is also designed to allow the structure to lift the boat sufficiently above the water. As the lift capacity increases, the number of air chambers increases. Larger structures require the user to evacuate the chambers at different rates to ensure a balanced movement. Users often complain about this requirement and the difficulty controlling it. U.S. Pat. No. 6,976,442 to Hey and U.S. Pat. No. 7,246,970 to Hey show boat lifts that use a cantilever method to lift the platform. The lift will be in the elevated position most of the time, so that in these systems, the rod surface spends most of its life exposed to the harsh marine environment. This can cause corrosion and pitting of the rod surface which will cause leaking of the hydraulic seals. Accordingly, there is a need for a boat lift for pilings and boat houses that will overcome the aforementioned problems.
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Q: Java day counter for discounts I am programming a card that allows you to pay bus tickets,it has a special discount for "Students"(80% off) in the first two tickets you pay in the day. I placed a variable that counts the amount of times you travel and then it discounts according if you haven't exceeded the 2 discounts that you are granted, but i cant find i way to make the variables value back to 0 when a day has passed. I must specify that the code i will pas you is an extension(inheritance) of the object TravelCard and there are several variables as priceXtravel, and balance that where inherited from it. public class StudentTravelCard { private double discount; private int discountCounter; public StudentTravelCard(int cardiD){ super(cardiD); discount = 0.8; } public void newTravel() { if(discountCounter < 2) { super.newTravel(); balance += (priceXtravel*discount); discountCounter ++; } else { super.newTravel; //discountCounter = 0;? what if they continue to travel on that day? } } } A: In your newTravel() you can just remove the commented line and add another method resetDay() to reset the back to 0 discounts in a new day. Of course resetDay() will have to be called by something that knows about the current time, etc. public class StudentTravelCard { private double discount; private int discountCounter; public StudentTravelCard(int cardiD){ super(cardiD); discount = 0.8; } public void newTravel() { if(discountCounter < 2) { super.newTravel(); balance += (priceXtravel*discount); discountCounter ++; } else { super.newTravel(); } } public void resetDay() { discountCounter = 0; } }
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India is truly a land of events and festivals! Such is the charm and grandeur of theirs that people from all across the world visit India to witness these events and festivals. Be it a Hindu or a Muslim, a Sikh or a Christian, in India there is something for everyone. After all, it is not for nothing that the country is known as the melting pot of all the cultures. In India, over 100 festivals are celebrated but out of them all, a few are celebrated pan India with much zeal and great fervour. So, without any ado, we would discuss a few popular festivals in India that you ought to witness, at least once in your lifetime. Here we go! 1. Holi Known as a festival that is all about colours, Holi is a very popular festival wherein people forget all their grudges and cover each other in different vibrant colours, making way for love and strong bonds. Before the day of the festival, on Holi eve, Holika Dahan takes place which is a bonfire around which people dance and have a whale of a time. On the day of Holi, people play with dry colours, wet colours, pichkari (water guns), water/colour filled balloons and whatnot. They end their day with some lip-smacking food. 2. Diwali This is undeniably one of the best events and festivals in India which is celebrated by one and all, no matter what religion, community or caste they belong to. Diwali is observed with much pomp and show wherein earthen lamps and candles are lit, the houses are decorated with lights and Rangoli. Apart from that, friends and families also exchange sweets, dry fruits, and other expensive gifts. People get in the festive mood by getting all decked up in new ethnic outfits ahead of the evening puja of Goddess Lakshmi and Lord Ganesha. 3. Janmashtami Another important religious festival of India, Janmashtami is a beautiful festival to witness, especially when you are on a pilgrimage tour in India in Vrindavan or Mathura. This day marks the birthday of the eighth avatar of Vishnu, Krishna. People, on this day, observe fast and, in the evening, celebrate the birthday pf bal gopal with much pomp and show. While some do just the evening puja, others cut the cake, dress Krishna up in new clothes as well as seat him in a palanquin, decorate their homes and prepare scrumptious dishes to treat the family. 4. Eid-ul-Fitr This one is the biggest Muslim festival that is, again, celebrated pan India. Eid-ul-Fitr marks the end of the religious month of Ramzan. People don the best of their outfits on this day. While the morning is dedicated to special community prayer, in the evening people visit their friends and relatives to exchange sweets. Elders give children or those younger to them Eidi which can either be money or gifts. 5. Dussehra Also known as Vijayadashami, Dussehra is celebrated a day after Navratri, a religious festival of 9 days, concludes. On this day and a few days ahead of this festival, Ramlila takes place which is enacting the popular scenes and stories of Ramayana. This enactment concludes with Ravana Dahan, a ritual wherein the effigies of Ravana, Kumbhkaran, and Meghnath are put on fire. This festival celebrates the death of Ravana, who was killed by Rama. 6. Independence Day It is nothing but the celebration of freedom, as it is on this day, in 1947, that India got freedom from the shackles of the British rule. The highlights of this day are tableaus, parades, 21 gunshots, the speech of the Prime Minister from the Red Fort and Indian flag hoisting. 7. Republic Day Apart from Independence Day, Republic day, one of the noted holidays in India, also evokes the feeling of patriotism in people. For the unversed, 3 years post-independence, in 1950, on this day, the Constitution of India came into being and India became a republic, after being under the British Raj for ages. This annual event is observed with great pride and much excitement, annually. To celebrate this day, grand parades are held that start from Rashtrapati Bhavan and end at Red Fort, via India Gate. 8. Rath Yatra Millions of people gather from all over the world everyday, especially in the month of July to see Rath Yatra. 9. Christmas While this festival is celebrated across India, Christmas is celebrated the best in one of the most popular travel destinations in India, that is, Goa. This day is quite significant in Christianity as it marks the birthday of Jesus Christ. Christmas is so much fun that children and adults are equally excited about this festival. On this day, families get to do everything together – preparing food, decorating home, the Christmas tree, and whatnot! Now, that you have all the details about these festivals, experience the same as well as the culture and heritage of India in all its essence during your stay in the country. For all the information on these festivals, events, Indian destinations, and cities, visit Adotrip, a one-stop solution to all your travel queries. Author Bio: Stella Wilson is an avid travel blogger currently working with Adotrip. She loves to write first-hand accounts of her travels. Apart from writing, her hobbies include reading and travelling. She has travelled extensively in India and her favourite destinations are Jaipur, Goa and Manali.
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From Rambles to Rants to Reviews Archive for September, 2008 The American Heritage Dictionary of the English Language defines a voyeur as 1. A person who derives sexual gratification from observing the naked bodies or sexual acts of others, especially from a secret vantage point. Voyeur is also a very hot and stylish story of romance and obsession by Jon Michaelsen, a wonderful new author. The story can be found in the MEN anthology on the Loveyoudivine His and His Kisses imprint from loveyoudivine Alterotica. The story follows Kevin, a gay accountant, who lives a rather mundane life before discovering a man in an adjacent high-rise that could well be his dream man. But what begins as an entertaining diversion, and a rather harmless fantasy soon spirals out of control to become a full-blown obsession. Along the way there is romance and steamy love to be found and enough Hitchcockian twists to make the master proud. (For fear of spoiling some of the suspense I am keeping the details rather vague). Voyeur is set in modern day Atlanta and Jon does a splendid job of evoking one of the most wonderful cities in America. Jon’s descriptive pictures make one feel as if they are truly there, cruising down Peachtree Street on a warm spring afternoon, the peach blossoms turning everything pink. (Having lived there for several years in the 1990s I was reminded of such diverse things as kudzu vines, the Allman Brothers Band at the Fox Theater, the Underground, MARTA, and going up to Seeger’s in Buckhead for one of the best meals ever!) Jon Michaelsen is one of the exciting new voices in the all male romance genre, and will next year have his first gay detective novel published by loveyoudivine. I am predicting that Jon is poised to break out as one of the premier romance writers in the field of gay fiction, as well as the author of suspense novels that will not only keep readers in suspense, but will keep them anxiously awaiting his next book. I can highly recommend Voyeur along with the rest of the MEN anthology that I have read (which is admitedly only two other stories). It is certainly hard for me to believe that The Angel Singers is the twelfth book in the Dick Hardesty mystery series. It doesn’t seem that long ago that The Butcher’s Son kicked off this wonderful series with a tale of arson and mayhem, and introduced us to one of the most endearing, not to mention enduring gay investigators, Dick Hardesty. The Angel Singers takes us into the world of a gay men’s chorus (and by the way gives quite good information and insight into that particularly fascinating world) and introduces us to a particulary nasty man named Grant Jefferson who happens to be sponsored by one of the choral group’s benefactors. It is not long however until Grant is scattered far and wide by a car bomb which lets the reader know there was some serious dislike for Mister Jefferson. Due to his nastiness there is no shortage of suspects for Dick to sift through on the way to revealing the somewhat surprising solution of this murder. However as entertaining as the solving of the crime is, it is in making the characters come to life that Grey really shines. Just like an elegant merlot chablais, this series has gotten better with time and age, each novel seeming to improve on the last to create a rich tapestry of not only Hardesty’s professional life, but also his home life. Dick, Jonathan and the adorable Joshua are characters we have come to love and to really care about, and I find the home and family life is every bit as entertaining as the mystery. Grey is a master at writing tongue-in-cheek wit, and there is plenty of that to be found in The Angel Singers. If you already love the Dick Hardesty series, as I do, you will love this one too, and if you have never read a Dick Hardesty book (and shame on you if you have not) this is as good as any of them as a place to start. As Robbie Burns wrote in his poem regarding the mouse turned up by the plough (To A Mouse, on Turning Her Up in Her Nest, With The Plough), “the best-laid schemes o’ mice an’ men aft gang agley”. Many years ago (i.e. the mid 1970s) as a very young writer, armed with a B.A. in Journalism, I began what I hoped would be a career in writing. And while there were early successes such as a volume of short stories published and two volumes of poetry published in addition to short-stories placed in various publications, the writing career was diverted by the intervention of life. The particular “plough” that disturbed my sod was a chance at careers in both music, and in the corporate business world, neither of which I can honestly say I regret. However a devastating and debilitating illness intervened to put an end to the music career as the hands upon the instrument would no longer cooperate with what the brain was coaxing them to do, and through a set of circumstances the Multiple Schlerosis also put an end to the business career. There followed many years of searching for direction, and the feeling that somehow my particular muse had taken permanent flight, before somehow arriving at the place where I made the decision that it is (past) time to jumpstart the writing career again. It came to me that after the ploughing comes the planting. So applying the seed of ideas to the fertile soil of the imagination, I found the ideas were indeed still there. To that end, I have at least three projects in various stages of completion which I will talk about soon, two being novels and one a short-story I am working on for an anthology. Now if the hands will only cooperate to tell the story my imagination is growing. At any rate this blog will be a place where I will not only discuss my own writing projects, but it will serve as a place to discuss the works of some of my writer friends and maybe do a fun interview or two of some of the writers I truly admire. (The B.A. in Journalism needs to be used occasionally afterall,) I also want to hear from you good folks that take time out of your busy day and kindly come by to peruse my words. If there is something you think should be here that is not please feel free to let me know, and if you like what you see here let me know that too.
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Backblaze Builds a Data Center It Hopes to Fill with 500 Petabytes of Data Building a data center in the cloud Cloud backup company Backblaze has a secret and it's a big one. How big? Try an exabyte. That's how much data Backblaze hopes to be able to store at its relatively new data center in the Sacramento area. We didn't know about it because Backblaze never revealed any details about the facility until now. It's located just outside of Sacramento and away from any earthquake fault zones and flood plains. It's also considered to be an area that's "very low risk" for tornadoes, so that's one less thing to worry about. Furthermore, the data center has SAS 70 Type II and ISO 9001 certifications and is PCI-DSS compliant, in case you're interested in counting bullet points. Backblaze says it's been a year since the Sacramento data center first began accepting customer data, and by September 2013, all new customer accounts were being serviced there. At the time Backblaze started looking for a new data center (August 2012), it was hosting 40 petabytes of data. "We expect to be able to store about 1/2 an exabyte (500 petabytes) of customer data at our new data center," Backblaze said. "That should last us a little while but just in case the operations folks are already scouting locations in Lake Tahoe for the next data center."
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package(default_visibility = ["//visibility:public"]) load( "@io_bazel_rules_go//go:def.bzl", "go_library", "go_test", ) go_test( name = "go_default_test", srcs = ["streaming_test.go"], embed = [":go_default_library"], deps = [ "//vendor/k8s.io/apimachinery/pkg/runtime:go_default_library", "//vendor/k8s.io/apimachinery/pkg/runtime/schema:go_default_library", "//vendor/k8s.io/apimachinery/pkg/util/framer:go_default_library", ], ) go_library( name = "go_default_library", srcs = ["streaming.go"], importpath = "k8s.io/apimachinery/pkg/runtime/serializer/streaming", deps = [ "//vendor/k8s.io/apimachinery/pkg/runtime:go_default_library", "//vendor/k8s.io/apimachinery/pkg/runtime/schema:go_default_library", ], ) filegroup( name = "package-srcs", srcs = glob(["**"]), tags = ["automanaged"], visibility = ["//visibility:private"], ) filegroup( name = "all-srcs", srcs = [":package-srcs"], tags = ["automanaged"], )
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Monday, 20 August 2012 Featured Photo: Union Flags in Long Acre I’m a great fan of flags and I’ve just loved seeing all of the Union Flags around the United Kingdom in the past 18 months or so. It used to be that the British seemed embarrassed of their flag but the Royal Wedding, Diamond Jubilee and Olympics have seemed to change that. I hope the flags are here to stay because it is such a beautiful flag. Not as pretty as the South African flag, naturally, but still one of the best. Which is your favourite flag and which do you like that are not your national flag? I’m quite fond of the American flag too. This photo was taken in Long Acre near Covent Garden on Saturday. Always look up. i love your flag! when i see it being incorporated into clothing, it reminds me of the mod '60's, like a pair of white go-go boots! but anytime i see the american flag being worn, it looks cheesy to me. i'm not sure why. and even though it's just a state flag, i kind of like that of arizona's. It's great to flag. We do not have so much flagging here but some use a small pennant. The Norwegian is of beautiful with the cross and colors. The Israeli flag is my favorite and great for several reasons and in Israel they have flags everywhere:-)
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1. Field of the Invention The field of invention relates to snow melting apparatus, and more particularly pertains to a new and improved snow melting heater mat apparatus wherein the same is arranged to be positioned adjacent a vehicle permitting ease of access to the vehicle. 2. Description of the Prior Art Snow melting apparatus in mat construction has been utilized in the prior art. The access to vehicles, particularly during snow storms, is awkward, difficult, and even dangerous due to melting and freezing of snow. The instant invention attempts to provide an organization to melt and direct snow through a cellular matrix of the mat structures to provide for a grid construction to permit a relatively non-slip surface, as well as directing melting snow therethrough. The prior art has addressed snow melting mats of various types and such mats are set forth in the U.S. Pat. Nos. 4,976,057; 3,976,855; 4,258,248; and 4,314,772. Accordingly, it may be appreciated that there continues to be a need for a new and improved snow melting heater mat apparatus as set forth by the instant invention which addresses both the problems of ease of use as well as effectiveness in construction and in this respect, the present invention substantially fulfills this need.
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Show Sort By Now it's easy to take along a raincoat for your dog wherever you go! Our Casual Canine® Rainy Day Dog Jackets are great for rainy days. Each jacket zips into a compact pouch for easy transport and storage.
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ZHYTOMYR, UKRAINE - Ukraine's Prosecutor General said on Friday that his office is reviewing all the cases that were closed by his predecessors, including several related to the owner of a gas company where former Vice President Joe Biden's son sat on the board. Ruslan Ryaboshapka's comments came amid an impeachment inquiry against U.S. President Donald Trump that relates to a call he made to the Ukrainian president asking him to investigate the Democratic presidential candidate and his son's work in Ukraine. Ryaboshapka told reporters in Kyiv that prosecutors are auditing all the cases that were closed or dismissed by former prosecutors, including several related to Mykola Zlochevsky, owner of the gas company Burisma that hired Hunter Biden in 2014, at the same time his father was leading the Obama administration's diplomatic dealings with Kyiv. Though the timing raised concerns among anti-corruption advocates, there has been no evidence of wrongdoing by either the former vice president or his son. “We are now reviewing all the cases that were closed or split into several parts or were investigated before, in order to be able to rule to reverse those cases where illegal procedural steps were taken," Ryaboshapka said. The Prosecutor General's Office later said that among the cases they are reviewing, there are 15 where Zlochevsky is mentioned. None of the Zlochevsky-related cases has been revived yet, they said. They did not specify how many, if any, were related to Hunter Biden's work at Burisma. Ryaboshapka was mentioned in the July 25 call between Trump and Ukrainian President Volodymyr Zelenskiy, who assured Trump that Ryaboshapka was “his man" and that he would resume investigations into Burisma. The prosecutor general insisted on Friday that he did not feel any pressure over the Burisma case. “Not a single foreign or Ukrainian official or politician has called me or tried to influence my decisions regarding specific criminal cases," he said. A whistleblower last month revealed that Trump in a phone call asked Zelenskiy to resume the probe into Joe Biden and his son. The July 25 call has since triggered an impeachment inquiry against Trump.
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Pe 28 iunie, reprezentantii societatii civile au sugerat, in cadrul primei dezbaterii referitoare la redefinirea abuzului in servicu, eliminarea pragului prin transformarea infractiunii in una "de pericol", fie stabilirea unui prag minim.Codru Vrabie, reprezentant al Asociatiei Funky Citizens, a sugerat modificarea infractiunii de abuz in serviciu, astfel incat ea sa nu mai fie o infractiune de rezultat, ci sa fie o infractiune de pericol, in acest fel nemaifiind nevoie de prag."Nu credem ca este neaparat nevoie de prag. (...) Parlamentul si dumneavoastra, prin Ministerul Justitiei, aveti posibilitatea sa inaintati o astfel de propunere Parlamentului, pentru ca tine de politica penala a statului roman, de filozofia penala din Codul penal. Va sugeram sa modificati infractiunea de abuz in serviciu din articolul 297, in asa fel incat ea sa nu mai fie o infractiune de rezultat, ci sa fie o infractiune de pericol. In momentul in care face aceasta redefinire, nu mai incape niciun fel de discutie despre vreun prag, pentru ca pragul este indisolubil legat de existenta rezultatului", a propus Codru Vrabie in cadrul dezbaterii.El a explicat ca in istorie a existat o perioada in care abuzul in serviciu era reglementat ca o "infractiune de pericol"."Infractiunea de abuz in serviciu, inca de la Dongoroz (Vintila Dongoroz ¬ n.r.) incoace, pare sa fie o infractiune de rezultat, insa, in Codul lui Cuza din 1865, infractiunea era una de pericol. In filozofia capitolului de infractiuni de serviciu exista si infractiuni de pericol, si infractiuni de rezultat, dar, daca ne uitam la abuzul in serviciu, ne intrebam care este valoarea ocrotita. Noi credem ca valoarea ocrotita este exercitarea atributiilor de serviciu cu respectarea legii. Nu poate sa fie ocrotita valoarea rezultata din incalcarea legii si cauzarea unei vatamari sau unui prejudiciu", a motivat Vrabie.In schimb, Asociatia APADOR-CH a sustinut ca este pentru introducerea unui prag rezonabil.Curtea Constitutionala considera, in motivarea deciziei prin care a fost solutionata exceptia de neconstitutionalitate ridicata de Bombonica Prodana, fosta sotie a presedintelui PSD, Liviu Dragnea, ca dispozitiile penale in vigoare cu privire la infractiunea de abuz in serviciu "sunt formulate in sens larg si in termeni vagi".Conform sursei citate, o astfel de omisiune are relevanta constitutionala, deoarece afecteaza drepturi si libertati fundamentale ale persoanei impotriva careia se formuleaza o acuzatie penala. In aceasta situatie, CCR considera necesara instituirea unui prag al pagubei si circumstantierea vatamarii produse prin comiterea faptei, in functie de care sa se aprecieze daca este sau nu vorba de o infractiune.CCR preciza, totodata, ca nu are competenta de a remedia acest viciu normativ, intrucat ar intra in sfera exclusiva de competenta a legiuitorului primar sau delegat si, astfel, si-ar depasi atributiile legale.
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Q: After Log.d(TAG, "downloadImgsUriArrayList:$downloadImagesUriList ") upload codes excute before for iterator's .addOnCompleteListener After Log.d(TAG, "downloadImgsUriArrayList:$downloadImagesUriList ") upload codes excute before for iterator's .addOnCompleteListener lead to var downloadImagesUriList: MutableList<String> = mutableListOf() is empty. How to solve this problem? var downloadImagesUriList: MutableList<String> = mutableListOf() //Upload images button upload_imgs_button.setOnClickListener { Log.d(TAG, "uploadImgsPath: $uploadImgsPath"); //Upload images to firebase storage if (uploadImgsPath != null) { for (uriForUpload in imagesList) { val imgNameUUID = UUID.randomUUID().toString() val withAppendedPath = Uri.withAppendedPath(uriForUpload, imgNameUUID).toString() var imgFileRef = uploadImgsPath!!.child(withAppendedPath) imgFileRef.putFile(uriForUpload) .continueWithTask { if (!it.isSuccessful) { it.exception?.let { throw it } } imgFileRef.downloadUrl }.addOnCompleteListener { if (it.isSuccessful) { var uriForDownload = it.result.toString() Log.d(TAG, "uriForDownload:$uriForDownload "); downloadImagesUriList.add(uriForDownload) } } } //The process will run here before downloadImagesUriList.add(uriForDownload) was excuted. //How to solve this problem? Log.d(TAG, "downloadImgsUriArrayList:$downloadImagesUriList "); var uploadedImages = UploadedImages( categoryDesignID, user!!.uid, downloadImagesUriList, Timestamp.now() ) //Save uploaded images path info to firestore firestore.collection("uploadedImages").add(uploadedImages) .addOnSuccessListener { Toast.makeText(context, "Upload successful", Toast.LENGTH_LONG) .show() } } else { Toast.makeText(context,"Please choose a category",Toast.LENGTH_LONG).show() } A: Firebase APIs, like most modern cloud APIs, are asynchronous, since they interact with a (potentially time-consuming) server. Instead of blocking your main thread while the cloud interaction happens, the clients allow your main code to continue, and then call back once the cloud API has completed its work. In your code that means that the Log.d(TAG, "downloadImgsUriArrayList:$downloadImagesUriList "); runs before the imgFileRef.downloadUrl. This explains why nothing is written to the database by add(uploadedImages): the download URLs haven't been determined yet, because the upload is still in progress. To solve this problem, all code that requires the download URL of an upload, must be inside the completion listener of that upload. The simplest way to do this, is to add a new URL each time the upload of that file completes: for (uriForUpload in imagesList) { val imgNameUUID = UUID.randomUUID().toString() val withAppendedPath = Uri.withAppendedPath(uriForUpload, imgNameUUID).toString() var imgFileRef = uploadImgsPath!!.child(withAppendedPath) imgFileRef.putFile(uriForUpload) .continueWithTask { if (!it.isSuccessful) { it.exception?.let { throw it } } imgFileRef.downloadUrl }.addOnCompleteListener { if (it.isSuccessful) { var uriForDownload = it.result.toString() Log.d(TAG, "uriForDownload:$uriForDownload "); downloadImagesUriList.add(uriForDownload) Log.d(TAG, "downloadImgsUriArrayList:$downloadImagesUriList "); var uploadedImages = UploadedImages( categoryDesignID, user!!.uid, downloadImagesUriList, Timestamp.now() ) //Save uploaded images path info to firestore firestore.collection("uploadedImages").add(uploadedImages) } } } The above will create a new document each time an upload completes. You'll either want to update the same document after each file completes or wait until the last file has uploaded before creating the document. There are many ways to do either, but a simple way is to simply keep a counter of how many files have completed uploading: var uploadedCount = 0 for (uriForUpload in imagesList) { ... }.addOnCompleteListener { if (it.isSuccessful) { var uriForDownload = it.result.toString() Log.d(TAG, "uriForDownload:$uriForDownload "); downloadImagesUriList.add(uriForDownload) if (uploadedCount++ >= imagesList.size) { Log.d(TAG, "downloadImgsUriArrayList:$downloadImagesUriList "); var uploadedImages = UploadedImages( categoryDesignID, user!!.uid, downloadImagesUriList, Timestamp.now() ) //Save uploaded images path info to firestore firestore.collection("uploadedImages").add(uploadedImages) } ... }
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Glucocorticoid therapy-induced skin atrophy. Glucocorticoids (GCs) are highly effective for the topical treatment of inflammatory skin diseases. Their long-term use, however, is often accompanied by severe and partially irreversible adverse effects, with atrophy being the most prominent limitation. Progress in the understanding of GC-mediated molecular action as well as some advances in technologies to determine the atrophogenic potential of compounds has been made recently. It is likely that the detailed mechanisms of GC-induced skin atrophy will be discovered and in vitro models for the reliable prediction of atrophy will be established in the foreseeable future. This knowledge will not only facilitate safety profiling of established drugs but will also foster further drug discovery by improving compound characterization processes. New insights into GC modes of action will guide optimization strategies aiming at novel GC receptor ligands with improved effect/side effect profile.
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Eiffel I'm in Love Eiffel I'm in Love is a 2003 Indonesian teen romantic comedy film directed by was Nasri Cheppy. The film stars Samuel Rizal and Shandy Aulia as the main characters, the film adaptation of the bestselling novel of the same name by Rachmania Arunita. Other people appearing in the film include Titi Kamal, Helmy Yahya, Didi Petet, and Hilda Arifin. The movie won an award for "Most Favorite Movie" and nomination for "Best Movie" at the 2004 MTV Indonesia Movie Awards. Cast Samuel Rizal as Adit Shandy Aulia as Tita Yogi Finanda as Ergi Titi Kamal as Intan Didi Petet Hilda Arifin Plot Based on the book with the same title, Eiffel I'm in Love tells the story about a teenage girl, Tita (Shandy Aulia), who led a perfect life. She had a lovely family, a patient boyfriend and 2 best friends who are always by her side. However, her mother was overly protective towards her and she is not allowed to go out. Her life completely changes when her parents good friend and his son, Adit (Samuel Rizal), came from France to stay with them. Tita was supposed to pick both of them from the airport. However, she waited at the wrong terminal and only realized that when Adit accidentally bumped into her and asked her whether she was the one who supposed to picked him and his father up. Adit was very cold to Tita from the start, however, her parents saw him as a reliable man and trust him to take care of their daughter. Things became worse when Adit told Tita that their parents were planning to forcibly match them as a couple. Extended version This film has an extended version, to review the story in this film in more depth. Awards and nominations External links Category:2003 films Category:Indonesian films Category:Indonesian-language films Category:2000s romantic comedy films Category:Teen comedy films Category:Films shot in Indonesia Category:Films shot in France
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