Two-dimensional stretched flow of Jeffrey fluid in view of Cattaneo-Christov heat flux is addressed. Effects of homogeneous-heterogeneous reactions are also considered. Suitable transformations are used to form ordinary differential equations. Convergent series solutions are computed. Impact of significant parameters on the velocity, temperature, concentration and skin friction coefficient is addressed. Analysis of thermal relaxation is made. The obtained results show that ratio of relaxation to retardation times and Deborah number have inverse relation for velocity profile. Temperature distribution has decreasing behavior for Prandtl number and thermal relaxation time. Also concentration decreases for larger values of strength of homogeneous reaction parameter while it increases for strength of heterogeneous reaction parameter. Importance of non-Newtonian fluids in boundary layer flow has increased. It is because of their extensive industrial and technological applications. The usual Navier-Stokes equation fails to describe the behavior of these kinds of flows. Mathematical formulation for such flows is in general complex. Such fluids cannot be examined by a single constitutive relationship between shear stress and rate of strain. The non-Newtonian materials are employed in applications related to biological sciences, geophysics and chemical and petroleum processes. Materials such as drilling muds, apple sauce, foams, soaps, sugar solution pastes, clay coating, ketchup, lubricant, certain oils, colloidal and suspension solutions are the non-Newtonian fluids. There are three types of non-Newtonian fluids e.g. differential, integral and rate types. Rate type fluids depicts the impact of relaxation and retardation time. Jeffrey fluid is one of the rate type materials. It shows the linear viscoelastic effect of fluid which has many applications in polymer industries. There are many examples of Jeffrey fluid including dilute polymer solution. Hayat et al.  analyzedHomogeneous and heterogeneous reactions are involved in many chemically reacting systems. Some of the reactions progress slowly or absolutely not, except in the presence of catalyst. The correlation between homogeneous and heterogeneous reactions is very difficult involving the production and consumption of reactant species at different rates both within the fluid and on the catalytic surfaces. Especially the chemical reaction effect is quite significant in food processing, hydrometallurgical industry, manufacturing of ceramics and polymer production, fog formation and dispersion, chemical processing equipment design, crops damage via freezing and groves of fruit trees. Merkin  analyzedIn industrial and engineering processes the heat transfer mechanism is very useful including nuclear reactor for cooling, energy production space cooling, biomedical applications such as heat conduction in tissues and magnetic drug targeting etc. Mechanism of heat transfer has been extensively described by classical Fourier heat conduction law . HoweverThe main purpose of present paper is to investigate the steady two-dimensional flow of Jeffrey fluid over a linearly stretching sheet. Effects of Cattaneo-Christov heat flux and homogeneous-heterogeneous reaction are clearly focused. Here we develop series solutions using homotopy analysis method –33. ConvTw and temperature far away from the sheet is T∞ (i.e Tw ≥ T∞) Flow analysis is carried out subject to homogeneous—heterogeneous reactions. Homogeneous reaction for cubic autocatalysis can be expressed as follows:We consider steady two-dimensional flow of Jeffrey fluid in the presence of Cattaneo-Christov heat flux. Fluid flow is induced by a linear stretching sheet. Sheet is at constant temperature a and b are the concentrations of the chemical species A and B and kc and ks are the rate constants. We assume that both reaction processes are isothermal. The conservation laws of mass, momentum, energy and concentration governing the present flow can be written below:u, v) are the velocities along  directions respectively, ν for kinematic viscosity, T for temperature, cp for specific heat, ρ for fluid density, α for ratio of relaxation to retardation times, λ1 for retardation time and q the heat flux satisfying the relationλ2 is the thermal relaxation time and k the fluid thermal conductivity. Following Christov 31]f(η)So Eqs  and 19)19) takesci (i = 1 − 4) are the constants.Since exact solution for velocity is given in Eqs  and 24)24). Howeq ∈  indicates the embedding parameter and ℏθ and ℏg are the non-zero auxiliary parameters then the zeroth order deformation problems areNg and Nθ are given byIf th order deformation equations areRθ,m(η) and Rg,m(η) have the following forms:The mθm, gm) comprising the special solutions (ci (i = 1 − 4) through the boundary conditions (38) have the valuesThe general solutions (θ and ℏg have much importance for the series solution convergence. For that purpose the ℏ – curves at 10th order of approximations are plotted (see θ ≤ −0.5 and −2 ≤ ℏg ≤ −0.5. Also the HAM solutions converge in the full range of η (0 ≤ η ≤ ∞) where ℏθ = −1 and ℏg = −1.5.The method of homotopy analysis gives us opportunity and a simpler way to adjust and control the convergence of the series solutions. The auxiliary parameters ℏtted see . Admissiθ′(0) and g′(0).In this section Figs –14 and Tf′(η) for several values of ratio of relaxation to retardation times α and Deborah number β. It is noted that momentum boundary layer decreases via larger α. Since α is inversely proportional to the retardation time of the non-Newtonian fluid so by increasing α there is reduction in retardation time and consequently the fluid flow reduces (β on dimensionless velocity f′(η) when α = 0.2. Here larger Deborah number leads to an increase in momentum boundary layer. It is due to the fact that β and stretching rate of sheet are proportional to each other (i.e. β = λ1c).Figs  reduces . Fig 3 rγ, ratio of relaxation to retardation times α and Deborah number β on dimensionless temperature θ(η). γ is shown in α. By increasing α we noted that there is increase in relaxation time and decrease in retardation time. Temperature enhances since increase in relaxation time is more than the retardation time. Temperature decreases for larger value of Deborah number . Effect of k1 on concentration profile is shown in k1 there is a decrease in concentration profile . k2 on concentration profile g. For increasing value of k2 the diffusion coefficient reduces and less diffused particles enhance the concentration. Effect of Schmidt number Sc on g(η) is shown in Sc. In fact Schmidt number is the ratio of momentum diffusivity to mass diffusivity. Therefore higher value of Schmidt number correspond to higher momentum diffusivity which in turn enhances the concentration profile. Behavior of ratio of relaxation to retardation times α on concentration distribution is analyzed in α there is decrease in g. β.Figs k1 on surface concentration g(0). One can see from the Fig that by increasing k1 there is a decrease in g(0). Variation of dimensionless wall concentration g(0) for different values of Schmidt number Sc is shown in Sc is increasing function of g(0).α the skin friction coefficient decreases while there is increase in skin friction coefficient via larger β. The values of shear stress at the surface are compared with previous published results in Cattaneo-Christov heat flux model is used to study the flow of Jeffrey fluid over a stretching sheet. Effects of homogeneous-heterogeneous are taken into account. Key points are as follows:Velocity profile is increasing function of Deborah number and decreasing function of ratio of relaxation to retardation times.Temperature decreases when Prandtl number and thermal relaxation time are increased.Effects of strength of homogeneous and heterogeneous reactions are opposite for concentration distribution.Concentration is more via larger Schmidt number.Surface drag force reduces when ratio of relaxation to retardation times is increased.Present results of surface shear stress agree well with previous published work.


STAT3 single-nucleotide polymorphism (SNP) rs4796793 has recently been reported to be associated with IFNα sensitivity in metastatic renal cell carcinoma. To translate this notion to melanoma, we scrutinized the impact of rs4796793 functionally and clinically in this cancer. Interestingly, melanoma cells carrying the minor allele of rs4796793 were the most sensitive to IFNα in vitro. However, we did not detect a correlation between SNP genotype and STAT3 mRNA expression for either melanoma cells or for peripheral blood lymphocytes. Next, we analyzed the impact of rs4796793 on the clinical outcome of 259 stage III melanoma patients of which one-third had received adjuvant IFNα treatment. These analyses did not reveal a significant association between the STAT3 rs4796793 SNP and patients’ progression free or overall survival when IFNα treated and untreated patients were compared. In conclusion, STAT3 rs4796793 SNP is no predictive marker for the efficacy of adjuvant IFNα treatment in melanoma patients.Interferon alpha (IFNα) is approved for adjuvant treatment of stage III melanoma in Europe and the US. Its clinical efficacy, however, is restricted to a subpopulation of patients while side effects occur in most of treated patients. Thus, the identification of predictive biomarkers would be highly beneficial to improve the benefit to risk ratio. In this regard, STAT3 is important for signaling of the IFNα receptor. Moreover, the  Malignant melanoma is an aggressive skin cancer originating from melanocytes. Due to the continuously raising incidence of melanoma among the Caucasian population, it represents an increasing health problem. Indeed, in the US, melanoma is one of the few common cancers with increasing incidence rates over the last decade, i.e., a 2.4% increase per year among white women and 2.1% among white men during 1999–2009 .The prognosis of a melanoma patient is largely dependent on the stage of disease. While early-stage melanoma can be cured in most cases by surgical excision of the tumor, already for patients with loco-regional disease beyond the primary tumor the prognosis is highly impaired. Among patients with nodal metastases, the 5-year survival rates were 78, 59, and 40% for patients with stage IIIA, IIIB, and IIIC melanoma, respectively. The sub-grouping is based on primary tumor characteristics, ulceration of the primary tumor, loco-regional spreading, and number of affected lymph nodes , adjuvant therapy would be indicated. The only currently approved adjuvant therapy – despite a recently reported positive clinical trial for adjuvant ipilimumab therapy of stage III melanoma – is interferon-α (IFNα). In 1995, high-dose IFNα-2b, and in 2011, pegylated IFNα-2b has been approved by the FDA for melanoma patients who are at high risk of recurrence. However, the percentage of patients indeed benefiting from adjuvant IFNα therapy is limited. Consequently, ever since the first reports demonstrating anti-tumor effects of IFNα for melanoma .signal transducer and activator of transcription 3 (STAT3) SNP rs4796793 with clinical response  in 33 candidate genes in metastatic renal cell carcinoma patients receiving IFNα therapy demonstrated a significant association of the response  and the TaqMan allelic discrimination assay for SNP rs4796793 genotyping was purchased from Applied Biosystems . Polymerase chain reaction (PCR) was performed according to the manufactures instructions in 20 μl volume reactions with 1 μl DNA on a 7500 Fast Real time PCR system (Applied Biosystems).STAT3 levels were determined for 35 peripheral blood lymphocytes (PBL) samples as well as 18 melanoma cell lines by real time PCR analyses in TaqMan technology using the comparative ΔΔCT method. PBL samples were obtained from melanoma patients who did not receive therapy at the time point the blood was drawn. Total RNA was isolated from approximately 3 × 106 cells. Samples of total RNA were subjected to reverse transcription. Primers and probe for STAT3 were designed with Primer Express software . The assay  detects all three STAT3 mRNA transcript variants. GAPDH (Applied Biosystems) served as endogenous control. The relative expression levels of STAT3 normalized to GAPDH and relative to the PBL sample pat1 heterozygote for the SNP was calculated as 2ΔΔCT with ΔΔCT =  – . CT is defined as the cycle when the threshold level of fluorescence is reached.Endogeneous Eleven melanoma cell lines were cultured in RPMI 1640 medium supplemented with 10% fetal calf serum. Four of these had the CC genotype , three the both genotype , and the remaining four the GG genotype .Nano . First, with the blank corrected extinctions, the growth of the cells compared to the basal metabolic rate determined on day 1 before addition of IFNα was calculated. The inhibitory effect of IFN was then determined by (growthmedium control − growthIFNα)/growthmedium control*100.In order to determine the impact of IFNα on melanoma cells, the MTS [3--5-(3-carboxymethoxyphenyl)-2-(4 sulfophenyl)-2H-tetrazolium] cell proliferation assay (Promega) was used according to the manufactures instructions. MTS is a tetrazolium reagent that is reduced by metabolically active cells. Melanoma cell lines were cultivated in triplicates in 96 well plates at 1000 , 4000 , or 8000 (MaMel71) cells per well with normal medium or supplemented with 51,200 U/ml IFNα for 4 days. Extinction at 490 nm and background at 650 nm were measured with the SpectrostarSerum from advanced melanoma patients from frozen serum banks hosted by Skin Cancer Unit, Mannheim and the Department of Dermatology, Würzburg served as DNA source for genotyping as previously described . In ordeSTAT3 expression of the different groups were compared by one-way ANOVA parametric when the data passed normality testing or else non-parametric, i.e., Kruskal–Wallis with Dunn’s post tests. Univariate as well as multivariate analyses Cox’s proportional-hazard regression model were applied when the models had passed the proportional-hazard assumption based on Schoenfeld residuals.Statistical analysis was performed with Prism  or Stata 11.2 . For univariate analyses, the Kaplan–Meier method was used to compare survival time between groups. Differences of survival time were assessed by the log-rank test. IFNα sensitivity or STAT3 rs4796793 genotype correlates with endogenous STAT3 expression in lymphocytes . However, within the two cell types, we could not detect a relevant difference of expression based on the SNP genotype  and 140 male (54.1%). The median age at diagnosis of stage III was 56.5 years. The median follow-up time from stage III diagnosis was 38.9 months; within this follow-up time, 159 patients developed distant metastases and 136 deaths were observed. About one-third (n = 76) of the patients had received IFNα as adjuvant therapy in stage III. Follow-up times for patients with or without adjuvant IFNα therapy were similar, but the treated cohort was significantly younger both at initial diagnosis or at progression to stage III (p = 0.008). Information on presence of absence of ulceration was available for 64.1% of the patients, i.e., 22% with, 42.1% without, and 35.9% with unknown ulceration status; these subpopulations were equally distributed among the two cohorts. Detailed patient and tumor characteristics and the genotypic frequencies of the STAT3 rs4796793 SNP are given in Table http://www.ncbi.nlm.nih.gov/snp/) ranging from 54.2 to 58.3% for CC, 33.6 to 39% for CG, and 3.3 to 8.8% for GG.Two patient cohorts, i.e., with or without adjuvant IFNα therapy, were included to be able to distinguish if STAT3 rs4796793 SNP genotype and DMFS . Despite the observation that the SNP genotype had no influence on DMFS in our patient groups, we tested for a potential effect of the STAT3 rs4796793 SNP genotype on OS by the Kaplan–Meier method. Again, the rs4796793 genotype had no impact on survival for patients receiving IFNα adjuvant therapy or not . For both the no-adjuvant-therapy group as well as the IFNα−adjuvant-therapy group, Kaplan–Meier analyses did not reveal any significant association between Melanoma is regarded as one of the most lethal skin cancers. This is still true, despite major breakthroughs in melanoma research resulting in new therapies, such as small molecule kinase inhibitors or immune checkpoint blocking antibodies, which have been proven to be both effective and beneficial in advanced melanoma patients . NeverthTAT3  has been reported to be associated with response to IFNα therapy in renal cell carcinoma patients (R2 = 0.14) but significant correlation between rs4796793 and STAT3 mRNA expression in Epstein–Barr virus transformed B-lymphocyte cell lines, i.e., a higher expression in cells being homozygote for the major allele  to IFNα was demonstrated (STAT5A or STAT5B mRNA expression, but to STAT3 mRNA expression, suggesting an association of STAT3 expression and IFNα efficacy.It is well established that IFN mediates its effect by STAT signaling . For exanstrated . InteresSTAT3 rs4796793 genotype and STAT3 mRNA levels, our in vitro results suggest that the presence of the minor allele increases the sensitivity of melanoma cells toward IFNα. Nevertheless, this in vitro effect did not translate into a clinical association. In the tested melanoma cohort receiving adjuvant IFNα therapy, no correlation between the STAT3 rs4796793 genotype and DMFS or OS was evident. It should be noted that given the number of patients and the event rate in the IFNα treated patients, a Cox regression for DMFS achieves 80% power at a 0.05 significance level to detect a hazard ratio of 1.51. Thus, it is rather unlikely that if the STAT3 rs4796793 SNP has a relevant impact, it would have been missed because of the size of the analyzed cohort. Consequently, the here presented data do not support a significant impact of the STAT3 rs4796793 SNP on IFNα efficacy in melanoma patients.Although we did not detect a correlation between the The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


An abnormal chromosome number, a condition known as aneuploidy, is a ubiquitous feature of cancer cells. A number of studies have shown that aneuploidy impairs cellular fitness. However, there is also evidence that aneuploidy can arise in response to specific challenges and can confer a selective advantage under certain environmental stresses. Cancer cells are likely exposed to a number of challenging conditions arising within the tumor microenvironment. To investigate whether aneuploidy may confer a selective advantage to cancer cells, we employed a controlled experimental system. We used the diploid, colorectal cancer cell line DLD1 and two DLD1-derived cell lines carrying single-chromosome aneuploidies to assess a number of cancer cell properties. Such properties, which included rates of proliferation and apoptosis, anchorage-independent growth, and invasiveness, were assessed both under standard culture conditions and under conditions of stress . Similar experiments were performed in diploid vs. aneuploid non-transformed human primary cells. Overall, our data show that aneuploidy can confer selective advantage to human cells cultured under non-standard conditions. These findings indicate that aneuploidy can increase the adaptability of cells, even those, such as cancer cells, that are already characterized by increased proliferative capacity and aggressive tumorigenic phenotypes. Candida albicans that developed resistance to antifungal drugs1218201213Fundamental to the survival of any organism is the balance between cell proliferation and cell death, which is required to ensure organismal development and to maintain healthy tissues and organs. The death and proliferation of normal, healthy cells is ensured by their ability to respond to and modulate growth and death signals. As opposed to healthy cells, cancer cells are characterized by the ability to escape such signals, thus becoming capable of evading apoptosis and proliferating independent of growth signals235Addressing the question of whether aneuploidy may confer a selective advantage to cancer cells can be very challenging, given that cancer cell karyotypes are very complex222324To explore whether aneuploidy confers a selective advantage to cancer cells, we made use of two trisomic cell lines derived from the diploid (2N = 46), chromosomally stable CRC cell line DLD12628221We first examined the proliferative capacity of the three CRC cell lines grown under various conditions by determining growth curves over a period of 6 days . We founTo assess whether the higher proliferation rates were linked to increased cell division rates, we quantified the mitotic index for the three CRC cell lines under all culture conditions . We founBecause overall proliferation rates are determined by the combined rates of cell division and cell death, and because cancer cells are known to evade apoptosisTo determine whether the observed mitotic indices and rates of apoptosis could explain the growth trends of the three CRC cell lines cultured under different conditions, we used a deterministic mathematical model  that tooin vitro, a phenotype that correlates with tumorigenicityWe next performed a soft agar assay to examine the ability of the three CRC cell lines to grow independent of anchorage −4 for each aneuploid cell line compared to diploid cells under all culture conditions; To assess the invasive ability of aneuploid CRC cells compared to the diploid parental cell line, we performed a matrigel invasion assay . We founWe next assessed the ability of aneuploidy to confer a selective advantage to non-transformed human cells by using diploid amniocytes (AF) and amniocytes with trisomy 13 (AF + 13). The proliferative capacity of these cells was assessed under standard culture conditions, in serum-free media, or in the presence of 5 μM 5-FU. We found that under standard culture conditions the diploid cells proliferated slightly better than the AF + 13 cells . HoweverTaken together, our data show that aneuploidy can confer a selective advantage to human cells under conditions of environmental stress, although in some of our assays and under certain culture conditions, there was no difference in behavior between diploid and aneuploid CRC cells. For both the CRC cells and the amniocytes, the diploid cells proliferated better under standard culture conditions. A similar proliferative advantage of euploid vs. aneuploid cells under standard culture conditions was previously shown in both yeast and mouse embryonic fibroblasts1011171417Candida albicans exposed to fluconazole1239414344453333Aneuploidy has been shown to cause transcriptomic changes that, for the most part, correlate with the specific aneuploid chromosome(s)1117263536113637173940Recent studies have shown that despite a general correlation between genes on the aneuploid chromosome and gene expression/proteomic profiles101735364849364950Our soft agar and matrigel invasion assays provided interesting observations in that aneuploid CRC cells were found to grow larger colonies and to be more invasive than diploid CRC cells not only under selective conditions, but also under standard culture conditions. One could envision anchorage-independent growth or migration through an extra-cellular matrix as challenges of their own. Therefore, the observation that aneuploid cells are more anchorage-independent and migrate better through matrigel regardless of the culture conditions, reinforces the idea that aneuploidy increases the fitness of cells, even those, such as cancer cells, that are already characterized by increased proliferative capacity and aggressive tumorigenic phenotypes.In several of our assays, DLD1 + 13 cells performed better than DLD1 + 7 cells, despite both displaying an advantage over DLD1 cells. DLD1 + 13 cells were recently shown to fail cytokinesis and acquire tetraploid/near-tetraploid karyotypes at significantly higher rates compared to the other two CRC cell lines52Given the advantage provided to cancer cells by aneuploidy, it is surprising that non-CIN CRC cells (such as DLD1) exist. However, this may be due to the fact that a combination of the high rates of mutation displayed by non-CIN CRC cellsIn conclusion, our work shows that addition of one extra chromosome is enough to confer a selective advantage to both primary and cancer cells, allowing aneuploid cells to perform better than diploid cells under a number of environmental challenges. These findings are consistent with the widespread aneuploidy observed in solid tumors56582.The DLD1 cell line was obtained from American Type Culture Collection ; the DLD1 + 7 and DLD1 + 13 cell lines were generated previously by microcell-mediated chromosome transfer2 for the duration of the experiment. For experiments in hypoxic conditions, cells were maintained inside a modular incubator chamber  in which humidity was maintained by addition of a 60 mm Petri dish containing 5 ml of water. Prior to each use, the chamber was flushed with 5% CO2, 1% O2, and N2 before being sealed and stored at 37 °C in an incubator. Cells were removed from the chamber for not more than one hour to conduct experiments, after which time the chamber was again flushed with 5% CO2, 1% O2, and N2 before being sealed and stored at 37 °C. Hypoxic conditions were confirmed using a Cyto-ID Hypoxia Detection Kit  and fluorescence microscopy detection according to the manufacturer’s instructions.For exposure to selective conditions, culture medium was prepared as follows: standard culture medium without FBS (Serum-free); standard culture medium with 10 μM 5-fluorouracil (5-FU) ; standard culture medium pre-conditioned in hypoxia chamber for 48 hrs (Hypoxia). For all experiments, except those in hypoxic conditions, cells were incubated with the appropriate culture media in a humidified incubator at 37 °C with 5% CO2. For exposure to selective conditions, culture medium was prepared as follows: standard culture medium without FBS (serum-free); standard culture medium with 5 μM 5-fluorouracil (5-FU) . A lower dose of 5-FU was used in AF compared to DLD1 cells due to the AF’s higher sensitivity to the drug.Passage 1–3 fibroblast cultures were established from surplus amniocentesis samples used in pre-natal diagnosis. Two cases of constitutional trisomy 13  and three diploid controls  were used in our study. FISH analysis of interphase nuclei stained with a chromosome 13 specific probe showed that the trisomic cell populations used in this study were highly homogenous (>95%) for the trisomic karyotype. The study acknowledged the ethics guidelines under Portugal national rules and according to the principles of the Declaration of Helsinki, and was approved by the Ethics Committee of Hospital de S. João-Porto . Informed consent forms with detailed information were provided to all patients. The study did not imply collection of extra material from the healthy female donors (only surplus cells/tissues were used); the study did not bring any direct benefits to the volunteers; there were no risks or costs for the volunteers; there was no access to patient clinical data ; participation was volunteer and could be interrupted at any time; there are no ethical impacts predicted; there will be no commercial interests. Amniotic fibroblasts were maintained in EMEM  supplemented with 15% FBS, 2.5 mM glutamine, and 1x antibiotic-antimycotic solution . All cells were kept in a humidified incubator at 37 °C with 5% CO5 cells per well. Following 24 hrs of growth in standard media, the cells were washed twice in PBS and re-incubated under selective culture conditions. For the 4-6-day samples, the media was replenished half-way through the experiment. At 24-hour intervals for six days, the media from one well of each DLD1 cell line was removed, the cells were washed twice with PBS and trypsinized. Cells were then vigorously re-suspended in media to a final total volume of 3 ml. From this, a 100 μl sample was thoroughly pipetted and mixed with an equal amount of 0.4% trypan blue solution , and subjected to cell counting. Cell counts were performed by hemocytometer  and averaged from four samples.To determine the proliferative capacity of CRC cells over time, we plated each DLD1 cell line in a 6-well plate  at a density of 1.5 × 105 cells per well. Following 24 hrs of growth in standard media, the cells were rinsed in PBS and re-incubated under selective culture conditions. One well was immediately fixed with cold methanol and stained with DAPI for nuclei quantification (day 0). The other six wells were fixed in methanol and DAPI-stained at 24-hour intervals over a six-day period (days 1–6). To quantify the number of cells, images of stained nuclei in a total of 100 neighboring fields (covering a 1 cm2 area) at two different locations in each well were acquired with a 10× objective on a Leica DMI 6000B motorized inverted epi-fluorescence microscope. The results from the two different stitched fields were averaged representing the number of nuclei per cm2. This number was then extrapolated to the total area of the well (9.6 cm2). The growth curves represent the mean ± S.D. values calculated from independent experiments using different trisomic and diploid samples.To determine the proliferative capacity of amniotic fibroblasts over time, we were unable to use the same method used in CRC cells due to technical difficulties. Instead, we used a different method, as described below. We plated each trisomy 13 and diploid control in 6-well plates  at a density of 0.8–1 × 105 CRC cells suspended in standard media were plated on 22 × 22 mm acid-washed sterile glass coverslips inside 35 mm Petri dishes. After 24 hours, cells were incubated under the appropriate culture conditions for additional 24 hrs. Cells were then washed twice with PBS, fixed with freshly prepared 4% paraformaldehyde , washed twice more with PBS, and DAPI stained. For each sample, the number of mitotic cells was counted over a total of at least 1,000 cells.1.5 × 105 cells suspended in standard media were plated on 22 × 22 mm acid-washed sterile glass coverslips inside 35 mm Petri dishes. After 24 hours, cells were incubated under the appropriate culture conditions for additional 24 hrs. Cells were then washed twice with PBS, fixed with freshly prepared 4% paraformaldehyde , washed twice more with PBS + 0.01% sodium citrate, and finally stained using an in situ cell death detection kit . Cells were then washed three times with PBS before DAPI staining. For each sample, the number of TUNEL positive cells was recorded over a total of at least 1,000 cells. Positive and negative controls were used according to the manufacturer’s guidelines.0.5 × 10For both mitotic index and TUNEL assay quantification, samples were viewed on a Nikon Eclipse TE2000-U inverted microscope  equipped with a swept field confocal system , a 100×/1.4 NA Plan-Apochromatic objective, and an automated ProScan stage . The confocal head was accessorized with a multiband pass filter set for illumination at 405, 488, 561, and 640 nm and illumination was obtained through an Agilent MLC400 monolithic laser combiner  controlled by a four channel acousto-optic tunable filter. Digital images were acquired with a HQ2 CCD camera . Stacks of images were acquired through the Z axis at 0.6 μm steps. Exposure time, Z-axis position, laser line power, and confocal system were all controlled by NIS Elements AR software  on a PC computer .5 cells and then poured on the bottom solidified agar layer. After solidification of the top agar layer, 2 ml of RPMI 1640 media (prepared according to the specific selective condition for each sample) were added and the samples incubated in a humidified incubator at 37 °C with 5% CO2, or in the hypoxia chamber. The colonies were grown for 22 days and media changed every 4–5 days. Ten randomly selected fields of view were imaged on a Nikon Eclipse Ti inverted microscope  equipped with a 20×/0.4 NA ADL phase contrast objective, phase-contrast transillumination, transmitted light shutter, ProScan automated stage , and a HQ2 CCD camera . For each field of view, Z-stacks were acquired by imaging 10 focal planes at 100 μm steps and colony number and size were measured for colonies present on different focal planes. The total number of colonies was quantified for all ten fields of view and the size of each colony was quantified by measuring the length of the longest axis. hTERT-RPE1 cells were used as a negative control and as a baseline for colony size measurements. Individual dot-like structures, corresponding to 1-few non-proliferating cells, were observed at low density in hTERT-RPE1 samples. The average size of these structures was 15 μm, and this was considered as the lower size limit for colony size measurements in DLD1 cell lines.1.5 ml of a 1:1 mixture of 2% agar  and 2× DMEM  media (prepared according to the specific selective condition for each sample) was poured evenly into a 35 mm Petri dish. After cooling, 1.5 ml of a 1:1 mixture of 1.4% agar  and 2× DMEM (prepared according to the specific culture condition for each sample) media was used to re-suspend 1 × 105 cells were re-suspended in RPMI 1640 media and plated onto the matrigel; 500 μl of media were also added to the bottom well and the chambers were incubated. After 24 hrs, both the media in the bottom well and that in the top chamber were replaced with media prepared according to the specific culture condition for each sample. After incubating for additional 24 hrs, non-invasive cells were scraped off the chamber side of the transwell membrane and invasive cells were fixed with 100% methanol, washed twice with PBS, and stained with a 1% Giemsa solution. Quantification was performed by light microscopy on a Nikon Eclipse TS100, using a 20×/0.4 NA ADL phase contrast objective and counting the total number of cells from 6 random fields of view.The matrigel invasion assay was performed using an 8 μm pore transwell PET membrane . The matrigel mixture  was reconstituted with the appropriate culture media to a concentration of 200 μg/ml and poured evenly over the transwell PET membrane; 10How to cite this article: Rutledge, S. D. et al. Selective advantage of trisomic human cells cultured in non-standard conditions. Sci. Rep.6, 22828; doi: 10.1038/srep22828 (2016).


The PEDOT nanostructures exhibit a narrow band gap (E = 1.69 eV) and are characterized by excellent ability to absorb light in visible and near infrared region. The novel PEDOT-based photocatalysts are very stable with cycling and can be reused without appreciable loss of activity. Interestingly, hollow micrometric vesicular structures of PEDOT are not effective photocatalysts as compared to nanometric spindles suggesting size and shape dependent photocatalytic properties. The visible-light active photocatalytic properties of the polymer nanostructures present promising applications in solar light harvesting and broader fields.The development of visible-light responsive photocatalysts would permit more efficient use of solar energy, and thus would bring sustainable solutions to many environmental issues. Conductive polymers appear as a new class of very active photocatalysts under visible light. Among them poly (PEDOT) is one of the most promising conjugated polymer with a wide range of applications. PEDOT nanostructures synthesized in soft templates  Nevertheless, TiO2 applications are limited because of a low quantum yield with the fast charge carriers (e−/h+) recombination and the necessity to use UV irradiation. Indeed, TiO2 can only be excited by UV irradiation with wavelengths shorter than 400 nm and it absorbs only 3-4% of the solar light impinging on the Earth’s surface452 for the most relevant photocatalytic applications such as detoxification and disinfection, water splitting and organic synthesis78922 nanocrystals with high photocatalytic activity under solar light have been developed2 in the visible light122 with Cu, Ag or Au nanoparticles significantly enhance the photocatalytic activity under UV and visible light1415The development of efficient and environmentally friendly approaches for energy conversion and storage is one of the pivotal challenges of the 212 and of poly(diphenylbutadiyne) (PDPB) nanofibers recently publishedIn the last few years, polymer nanostructures have attracted a lot of attention for energy conversion and storage applications212218via chemical oxidative polymerization of EDOT monomers using FeCl3 as an oxidizing agent as shown in Supplementary Scheme S1We have developed a soft template mediated controlled synthesis of PEDOT nanostructures with tunable morphology. Hexagonal mesophases composed of oil-swollen surfactant-stabilized tubes arranged on a triangular lattice in salted water and doped with EDOT monomers in the oil phase were used as soft templates 25. Polym−3 mol L−1 and 6.1 × 10−5 mol L−1 respectively) in the presence of the polymer  was studied prior to the photocatalytic tests but showed no significant change in the concentration of phenol and MO in solution  and of silver modified P25 TiO2 2, Ag-TiO2, and PEDOT nanospindles, after irradiation for 60 min, 15 min, and 10 min respectively. However, only 30% degradation has been achieved for PEDOT vesicles under identical reaction conditions. In fact, poly(diphenylbutadiyne) (PDPB) nanofibers exhibited a UV light induced photocatalytic activity with 82% degradation of phenol after long irradiation (270 min) but this activity is even lower than that of bare or modified TiO2Waste waters generated by the textile industries contain considerable amounts of non fixed dyes and especially of azo-dyes which are toxic to aquatic life and create serious environmental pollution. Methyl orange (an azo dye) is a fairly stable and persistent dye pollutant under visible light irradiation without a photocatalyst. The photocatalytic activities of PEDOT were evaluated for the degradation of phenol and methyl orange (MO) (taken as model pollutants) in water under UV and visible light. The blank test showed that almost no photolysis of MO was observed under similar experimental conditions. At the same time, the dark absorption test  source using a nanoIR instrument that can survey the various regions of the polymer via AFM topography imaging25−) and holes (h+), and the catalytic reactions induced by these species. A high photocatalytic activity is closely related to an efficient separation of the photoexcited electron-hole pairs generated in the photocatalyst after its excitation. The organic pollutants and dyes can be photodegraded via a photocatalytic oxidation process7• and O2•− radicals are involved in the photocatalytic oxidation process2•− radical (E0(O2/O2•−) = −0.33 VSHE)Photocatalysis involves generation of charge carriers, i.e. excess electrons , causes a decrease in the production of O2•− in the photocatalytic system aminomethane (Tris) as a probe• generated on the surface of the PEDOT during photocatalysis reaction. It can be seen that formation of HO• increases in the photocatalytic oxidation process with irradiation time as shown in To probe the role of the excess electrons in the photocatalytic process, experiments were conducted in the presence of Cuc system , which ip-doping (oxidation) and n-doping (reduction) are irreversible processes, and the values of the peak potentials vs. Ag/AgCl are + 0.139 V (oxidation) and −1.552 V (reduction) for PEDOT nanospindles. This reveals the onset of oxidation and reduction processes occurring at lower potentials having a much lower energy gap around 1.69 eV than TiO2 (3.2 eV). When illuminated with photons of energy exceeding  the band gap (E ≥ 1.69 eV or λ ≤ 733 nm), excess electrons and holes are formed in the conjugated polymer chains.In order to understand the mechanistic aspects of visible light responsive photocatalysis, cyclic voltammetry (CV) measurements were used to calculate the experimental HOMO and LUMO energy levels from the ionization potential and the electronic affinity, respectively and determine the band gap of PEDOT nanospindles . We foun2 or even PDPB. Upon excitation and promotion of an electron from the valence band to the conduction band (across the band-gap) of a semiconducting material, there exists a tremendous electrostatic driving force to recombine electrons and holes which becomes a major rate-limiting factor in a catalytic process. Based on the analyses, the proposed schematic diagram of photoexcited electron-hole separation process is shown in 2•− superoxide radical. This effective separation of photogenerated electron–hole thereby promotes superior photocatalytic activity. Meanwhile, the photogenerated holes on PEDOT  cannot produce hydroxyl radicals. These species have a very high oxidation potential (E0(HO•/ H2O) = 2.27 VSHE) and are involved in the photooxidation reactions with TiO2. However, HO• radicals can be formed by the following reactions  compared to TiOEquation , 5:2•−, photo induced h+ , and HO• radicals mediated degradation of organic pollutant with effective charge separation in PEDOT nanospindles  is much lower in comparison to that of PEDOT nanospindles (0.4 S/cm). Although both polymer structures can absorb light in visible region, photo-induced electrons are less mobile (i.e. lower conductivity) in PEDOT vesicle structures and the recombination of charge carriers may be faster. Hence less electrons could escape the recombination and reach the surface. This probably explains the lower photocatalytic degradation of organic molecules observed for PEDOT vesicles compared to PEDOT nanospindles. Both PEDOT structures (vesicles and nanospindles) showed no X-ray diffraction pattern indicating that they were not well crystallized. The difference in the photocatalytic activity between nanospindles, vesicles and bulk PEDOT might be due to larger size and to the presence of more defects in vesicles (sub-micron size) and bulk PEDOT favoring higher e−–h+ recombination. Note that such a behavior has also been recently observed in the case of PDPB, where the photocatalytic activity was much higher for nanostructures than for the bulk polymer  have therefore excellent ability to absorb light in visible and near infrared regions. Our results demonstrate that PEDOT nanostructures show exceptional high photocatalytic activities under UV (even higher than P25-TiO2) and visible light (higher than PDPB nanofibers) and are of huge potential for environmental remediation. This photocatalytic activity appears only at the nanoscale range. We show that the photocatalytic activity depends also on the shape of the PEDOT nanostructures. The PEDOT nanospindles have been found to be very stable photocatalysts with cycling. The photocatalytic oxidation reactions involve the oxidative O2•− and HO• species. Our results demonstrate that conducting polymer nanostructures constitute a new class of photocatalysts for environment remediation. Other applications of these nanostructures in self-cleaning surfaces, and hydrogen generation are under investigation.In summary, Poly nanostructures have been synthesized by a facile and reproducible chemical oxidative method using hexagonal mesophases as soft templates at room temperature. The PEDOT nanostructures with much narrower band gap (E = 1.69 eV) compared to TiO4 (>98%), phenol (C6H5OH) and methyl orange were purchased from Sigma-Aldrich. Titania  was obtained from Evonik for comparative photo degradation by polymer nanostructure. N2 gas (purity > 99.995%) was purchased from Air Liquide. All compounds were used as received. Ultrapure water  and ethanol  were used as solvents. All experiments were performed at room temperature.3,4-ethylenedioxythiophene (EDOT), iron (III) chloride, cetyltrimethylammonium bromide (CTAB) (≥98%), sodium chloride, toluene (>99%), pentanol (≥99%), silver perchlorate AgClO3). EDOT and/or FeCl3 were dissolved separately in toluene and added to the viscous micellar solution during mesophases preparation. Evidently, EDOT and FeCl3 were never mixed together before this step in order to avoid bulk polymerization.The swollen hexagonal mesophases were prepared following the previously published method with some modifications. This system exhibits oil in water (O/W) direct phase structure made of hexagonally packed nonpolar cylinders filled by toluene and stabilized by a monolayer of cationic surfactants and cosurfactants, which are surrounded by a continuous water domain. Additionally, the swelling of the mesophases was varied by changing the volume ratio of oil over water (O/W). We varied both O/W ratio and NaCl concentration simultaneously. For example, mesophases with O/W = 1.5 and NaCl at 0.1 M or with O/W = 2.5 and NaCl at 0.3 M were prepared at fixed EDOT concentrations. The hexagonal mesophases were made of a mixture of cetyltrimethylammonium bromide (CTAB) as surfactant, salted water (NaCl), toluene as oil and pentanol as cosurfactant. Typically, 1.03 g of CTAB was dissolved in 2 mL of an aqueous solution containing salt (0.1 M NaCl). After a vigorous agitation for few minutes at 50 °C, the surfactant was completely dissolved giving a transparent and viscous micellar solution. The subsequent addition of 2.98 mL of toluene in the micellar solution under stirring induced the formation of a white unstable emulsion. The cosurfactant (20 μL of pentanol) was then added to the mixture which was strongly vortexed for a few minutes. This led to a perfectly translucent, birefringent and stable gel consisting in a hexagonal mesophase for PEDOT vesicles structures. For another composition (with O/W = 2.5 and NaCl at 0.3 M), 4.42 mL of toluene and 30 μL of pentanol have been used to prepare the mesophases following the same methodology for PEDOT nanospindles. According to the same procedure, other mesophases were also prepared in the presence of both the monomer (EDOT) and the oxidant  (10% of mass) and initiator benzoin methyl ether (BME) (1%) in the micellar solution under stirring leads to a white unstable emulsion. A cosurfactant, pentanol-1 (420 μL), was then added to the mixture, which was then strongly vortexed for a few minutes. This led to a perfectly colorless, translucent, birefringent and stable gel: a hexagonal mesophase. The doped mesophases with the monomer and the initiator for polymerization were used as soft templates to synthesize polymer nanostructures induced by irradiation using UV light with an Oriel 300 W Xenon UV-visible lamp at a distance of 5 cm for 12 hours.The swollen hexagonal mesophases were also prepared for the synthesis of PDPB polymer nanostructure. Typically, 1 g of the surfactant (Sodium Dodecyl Sulfate) was dissolved in 2 mL of 0.3 mol.LAfter reaction, the materials were extracted in a water-ethanol mixture, centrifuged, and washed several times to eliminate the surfactant, the cosurfactant and the salts.+ in the TiO2 suspension (2 wt %). An ethanolic solution containing AgClO4 (2 × 10−3 M) and TiO2 (P25) in suspension is first sonicated for 3 min, degassed with nitrogen, and irradiated (under stirring) with a 60Co panoramic gamma source (dose rate = 2.3 kGy h−1). The silver ions were reduced by the solvated electrons and the alcohol radicals induced by solvent radiolysis and 1 h 20 min exposure time (3.2 kGy) was necessary to reduce all the silver ions. The modified TiO2 photocatalysts were separated by centrifugation and dried at 60 °C. The modified catalyst (Ag-TiO2) has been used for methyl orange and phenol degradation.The photocatalysts were obtained by radiolytic reduction of Ag6H5OH) in water. The light beam emitted from Oriel 300 W xenon lamp was passed through an IR water filter and a UV cut-off filter (λ > 450 nm) before being focused onto a cylindrical Pyrex reactor through a quartz window. The photodegradation reaction of phenol was carried out using a 10 mm optical path quartz cell reactor containing 3.5 mL of 3.7 × 10−3 mol L−1 of phenol in the presence of 1 g L−1 of bulk, vesicle or spindles PEDOT. The PEDOT was added in the phenol solution and magnetically stirred for 10 minutes in the dark to ensure the adsorption equilibrium of phenol and MO prior to irradiation. The solution was then irradiated with a xenon lamp (under UV and visible light) and bubbled with O2 at a fixed flow rate along with magnetic stirring. A 0.5 mL aliquot was collected from the reactor at different time points. In case of P25, after degradation reaction, the solution was centrifuged to separate the catalyst and obtain a transparent solution. High-performance liquid chromatography (HPLC) was used to determine the concentration of phenol and to study its degradation. A Varian Prostar 230 ternary gradient pump was combined with a Prostar 330 photodiode array detector (D2 lamp). For elution, an isocratic mobile phase consisting of 75% H2O and 25% acetonitrile (ACN), at a 1 mL min−1 flow rate, was used, with detection at 270 nm. The column was an Adsorbosphere C18 reverse phase  combined with an All-Guard cartridge systemTM . For data acquisition, Star software was used.The photocatalytic activity under UV-visible illumination of the PEDOT has been tested by photodecomposition of phenol , the conditions were the same as those used for phenol except that the initial concentration of MO was 6 × 10Multiple photocatalysis experiments were performed under identical reaction conditions to determine reproducibility. After the completion of the degradation of MO and Phenol, PEDOT spindles were recovered by filtration, and then washed thoroughly with water. The recovered PEDOT spindles were dried at 30 °C overnight. This used catalyst was re-employed in the next cycle under identical conditions.2 (P25TiO2), Ag nanoparticle modified TiO2 (Ag-TiO2) diluted in 1 mL of 0.2 M acetoacetanilide in ethanol and 2.5 mL of 4 M ammonium acetate. Consequently, a dihydropyridine has been formed having a maximum absorption wavelength of 368 nm. The absorbance has been measured by a spectrophotometer.In this method, 1.5 mL of reactant solution was extracted after photo irradiation of organic pollutants in the presence of PEDOT spindles, TiOExperiments with the total organic carbon (TOC) technique were conducted to study the mineralization of phenol and MO at different irradiation times. TOC was measured by using a Shimadzu TOC-LCSH. TOC was measured by IR after complete oxidation by catalytic combustion at 680 °C on exclusive platinum catalyst, the inorganic carbon being removed by a previous acidification and air purging.How to cite this article: Ghosh, S. et al. Visible-light active conducting polymer nanostructures with superior photocatalytic activity. Sci. Rep.5, 18002; doi: 10.1038/srep18002 (2015).


Vibrio cholerae isolates from the Democratic Republic of the Congo during 1997–2012 and found increasing antimicrobial drug resistance over time. Our study also demonstrated that the 2011–2012 epidemic was caused by an El Tor variant clonal complex with a single antimicrobial drug susceptibility profile.We analyzed 1,093  Vibrio cholerae . We applied whole-genome sequencing and multiple locus variable-number tandem-repeat analysis (MLVA) to clarify the mechanisms behind the aggressive epidemic of 2011–2012 that spread throughout the country, affecting regions to which cholera was not endemic  served as controls. Isolates were tested against 9 antimicrobial drugs as follows: ampicillin (10 µg), chloramphenicol (30 µg), sulfamethoxazole/trimethoprim (1.25 + 23.75 µg), tetracycline (30 µg), doxycycline (30 µg), norfloxacin (5 µg), ciprofloxacin (5 µg), nalidixic acid (30 µg), and erythromycin (30 µg) (bioMérieux). Interpretation of inhibition diameters  was performed according to Clinical and Laboratory Standards Institute guidelines  were performed as previously described  collected at epidemic onset by using a HiSeq Illumina System  as previously described , revealed that the strain was an El Tor variant with CTX-3 type phage and a RS1 satellite phage. Phylogeny analysis situated this DRC strain close to the major Kenyan clade in the most recent wave of the seventh pandemic (data not shown).To examine the particular 2011–2012 epidemic that spread throughout the DRC (V. cholerae clinical isolates from the DRC from 1997–2012 highlighted a loss of sensitivity to leading antimicrobial drugs, although strains remain susceptible to fluoroquinolones. However, a risk for emergence and spread of fluoroquinolone-resistant strains exists, as has been shown elsewhere in Africa (Analysis of a panel of V. cholerae subpopulation, which rapidly diffused countrywide. Furthermore, sequence analysis showed that the clone responsible for this epidemic, an El Tor variant with CTX-3 type phage, falls close to the major Kenyan clade in wave 3 of the seventh pandemic. This observation correlates with a 2011 study demonstrating that the seventh cholera pandemic had been caused by specific strains originating from a unique ancestral clone that have spread globally in successive waves (V. cholerae population.Our findings also provide new insight regarding the cholera epidemic of 2011–2012. This epidemic appears to have been caused by the expansion of a specific V. cholerae isolates provide extensive insight into the mechanisms of cholera epidemics. MLVA and whole-genome sequencing are powerful tools for elucidating epidemic dynamics because these methods have been used to link distinct outbreaks and identify the origin of certain epidemic V. cholerae strains (This study demonstrates that molecular and microbiological analyses of


These Magnéli phases (TinOn−12) present well-defined crystalline structures, i.e., their deviation from stoichiometry is accommodated by changes in space group as opposed to point defects. We show that these phases exhibit intermediate bands with an electronic quadruple donor transitions akin to interstitial Ti defect levels in rutile TiO2. Thus, the Magnéli phases behave as if they contained a very large pseudo-defect density: ½ per formula unit TinOn−12. Depending on the Fermi Energy the whole material will become charged. These crystals are natural charge storage materials with a storage capacity that rivals the best known supercapacitors.Defects in semiconductors can exhibit multiple charge states, which can be used for charge storage applications. Here we consider such charge storage in a series of oxygen deficient phases of TiO Li-ion batteries have played the major role in energy storage up to now3452 are known to present unintentional n-type doping at ambient conditions, owing in part to intrinsic point defects related to oxygen deficiency: oxygen vacancy (VO) and titanium interstitial (Tii)1617nOn−12 also find wide spread applications22Titanium oxides are important materials for applications in photocatalysis89111314A few reports on the thermochemistry242728293019114O7 and Ti5O9, as well as of the corundum Ti2O3 phase, while in contact with a reservoir of electrons. We show that these TiO phases present a series of properties akin to Tii-containing rutile TiO2, such as mid gap states and charge state transitions. We show that the intermediate band typical for the Magnéli phases can donate electrons to an electron reservoir, leading to a new electronic phase that resembles charged defects in a semiconductor, even though they contain no crystallographic defects. The combination of such properties is shown to enable charge storage in these systems in such an efficient way that they can rival the best supercapacitors to dateIn this manuscript we study the stability and electronic structure of Magnéli phases TinOn−12 (n > 4). In general, for n > 37 the crystal structure is still rutile TiO2, containing point defects or Wadsley defects. Further removal of oxygen (a decrease in n) leads to the reorganization of the crystal into these new crystallographic phases19n TiO6 octahedra units along the c axis bounded by a corundum structure 34352 and corundum Ti2O3 parts. The corundum-like boundaries of the rutile-like region of the Magnéli phases are usually referred to as shear planes. A detailed view of the corundum structure is shown in The Magnéli phases have the general oxygen-deficient chemical formula Tin times along the c vector from the origin are in turn dislocated in the i.e., the vector 2 and Ti4O7. From the perspective of (a) and (b) one can see that the oxygen deficiency of such compounds is better described by extra Ti atoms occupying interstitial positions of the TiO2 matrix, rather than by oxygen atoms missing at specific lattice sites, i.e., oxygen vacancies.A model structure of these oxygen deficient phases can be obtained from rutile via a shear operation nOn−12 phases present an intermediate band27282O3 and Ti4O7 in 5O9 in 21617pseudo-defects inside the Mangéli phases. As these phases present a high concentration of such pseudo-defects, one can think of this intermediate band as the spatially-extended generalization of point defects. Importantly, this pseudo-defect band lies close to the rutile TiO2 CBM, indicating that its occupation can be tuned by the use of appropriate leads, leading to charging of the material. We investigate this charging process by electronic structure calculations of the first two Magnéli phases Ti4O7 and Ti5O9 and corundum-phase Ti2O3.From the electronic point of view, these oxygen-deficient Ti2 and the ensuing formation of these oxygen-deficient phases can be described by two processes: (i) either the Magnéli phase is formed by the removal of oxygen and consequently the formation of ordered VO planes  and a reservoir of electrons with the chemical potential at EF. The formation enthalpy 2 as a host material is given byOur calculations include a reservoir of atoms at constant chemical potential EH and ED(q) are respectively the total energies of the system before (TiO2) and after (TinOn−12) exchanging mα atoms with the reservoirs. The total energies ED and EH are obtained from density-functional calculations performed using the VASP codeet al.2 matrixEF is given with respect to the VBM of TiO2 (EV BM), and ΔV is a band-bottom alignment correction used to place all energies at the same reference, obtained from core level shiftsp4s3d electrons were considered as valence electrons whereas the 2s2p configuration was considered for O atoms. Core level energies were obtained solving the Kohn-Sham equations for these inner level electrons subjected to a potential given by the pseudopotential method projector-augmented-wave (PAW) scheme2 molecule while the same quantity for the titanium atom was obtained from a bulk calculation of the hcp structure of metallic Ti.where pseudo-defects in Magnéli phases for different charge states q. The chemical potentials one should use for the expression could be either μO for the removed oxygen (mO > 0) or μTi for the added titanium (mTi < 0). We choose to discuss only the situation where the Magnéli and corundum phases are formed via the insertion of Ti atoms  as the most stable (lowest formation energy) spanning the entire rutile TiO2 band gap, while both Ti4O7 and Ti5O9 present the same trend from the VBM up to ε(+4/0) = ECBM − 0.36 eV and 0.48 eV respectively. The position of ε(+4/0) marks an abrupt transition from the +4 state to the neutral state. Interestingly this transition lies close to the very same ε(+4/0) for the isolated Tii in rutile TiO2 (0.29 eV)nOn−12 structures behave in a fashion similar to TiO2 with intrinsic defects (Tii or VO). An important distinction must be taken at this point, since the presence of extrinsic defects can lead to different behaviors. For example, nitrogen impurities in the Magnéli phases lead to an electron-hole compensation effect that can significantly alter properties such as the bandgap and photocatalytic activitypseudo-defect induced intermediate band in a similar fashion as it is done to mid gap states of isolated defects inside semiconductors. Moreover both Ti4O7 and Ti5O9 present negative-U behaviori point defects inside rutile TiO2Formation enthalpies for the TinOn−12 structures can be understood from the Projected Density of States (PDOS) and real-space projections of selected states. 5O9 as a point in case—Ti4O7 presented a similar behavior (see intermediate band akin to isolated defect states. These states are mostly of Ti(d) character—as are the unoccupied bands—delocalized over several Ti atoms, as shown in 46Tii in rutile TiO2pseudo-defects in the Magnéli phases are facilitated by a self-regulating response mechanism4648The nature of the charged state in the Tivior see . The neupseudo-defect corresponding to the quadruple donor transition observed, as well as the maximum capacity of the intermediate band to accommodate 4 electrons—two electrons for each of the two VO’s, or alternatively, four electrons for a single Tii, according to the previous discussion. Using this and considering a device operating at a 1 V potential, the theoretical maximum capacitance is approximately 1300 F/g for Ti2O3, 600 F/g for Ti4O7, and 500 F/g for Ti5O9, placing those systems at par with materials used to build supercapacitors. One of the best supercapacitors developed until now is based on nickel hydroxide nanoflakes on carbon nanotube composite electrode, with a capacitance of 3300 F/gTo estimate the storage capacity of these Magnéli phases, we consider a maximum of 4 holes per pseudo-defects, i.e., they behave akin to Tii doped rutile TiO2 with a concentration of ½ quadruple donor defects per formula unit TinOn−12. These pseudo-defects are characterized by an intermediate band that can be charged, thus, the material can become charged and used for high-capacity charge storage. We propose that the same behavior shown here for the oxygen deficient TiO phases exists in other semiconductor materials. The required condition is the presence of the intermediate band with a large enough density of states, which we expect to be the case in other materials that present stable phases over a wide range of stoichiometries.In conclusion, we have performed electronic structure DFT calculations to asses the formation and electric charging of the TiO Magnéli and corundum phases. We show that these materials contain How to cite this article: Padilha, A. C. M. et al. Charge storage in oxygen deficient phases of TiO2: defect Physics without defects. Sci. Rep.6, 28871; doi: 10.1038/srep28871 (2016).


Thermoproteus species even though they contain SRP19 and SRP54 proteins. Here, we show that genome rearrangement events in Thermoproteus tenax created a permuted SRP RNA gene. The 5'- and 3'-termini of this SRP RNA are located close to a functionally important loop present in all known SRP RNAs. RNA-Seq analyses revealed that these termini are ligated together to generate circular SRP RNA molecules that can bind to SRP19 and SRP54. The circularization site is processed by the tRNA splicing endonuclease. This moonlighting activity of the tRNA splicing machinery permits the permutation of the SRP RNA and creates highly stable and functional circular RNA molecules.Signal recognition particles (SRPs) are universal ribonucleoprotein complexes found in all three domains of life that direct the cellular traffic and secretion of proteins. These complexes consist of SRP proteins and a single, highly structured SRP RNA. Canonical SRP RNA genes have not been identified for some DOI:http://dx.doi.org/10.7554/eLife.11623.001 Cells make many proteins that are eventually released outside the cell or inserted into the cell’s membrane. As these proteins are still being made, they are captured by a “signal recognition particle” (or SRP); this molecular machine then guides the newly forming protein to the cell’s membrane. SRPs are found in all living organisms on Earth and contain several different proteins and a short RNA molecule. However, a few species belonging to the archaeal domain of life did not seem to contain an identifiable gene for the RNA component of the SRP.Thermoproteus tenax, a single-celled microbe which grows in the absence of oxygen and at temperatures of up to 95°C.Now Plagens et al. have sought to solve the mystery of the “missing” component of this essential protein-targeting machine. This involved searching through the RNAs that are produced by an archaeon called Plagens et al. discovered that the “missing” SRP RNA gene had not yet been identified because rearrangements in this archaeon’s genome had swapped the left and right portions of the SRP RNA gene. Further experiments revealed that the correct sequence order is restored in mature SRP RNA molecules by the two ends of the molecule being linked to form a circle. These RNA circles are made by the cellular machinery that normally removes the unneeded sections from other RNA molecules .Circular RNA is much more stable at high temperatures and does not degrade easily, and Plagens et al. suggest that this particular arrangement is therefore especially advantageous for this species. Future work will now aim to work out which selective pressures favor the evolution of such fragmented RNAs.DOI:http://dx.doi.org/10.7554/eLife.11623.002 Thermoproteus (e.g. Thermoproteus tenax and Thermoproteus uzoniensis) do not contain canonical SRP RNAs and SRP RNA genes are not annotated  that bind to the ribosome and recognize signal peptides in secretory proteins . SRP binnnotated . Genes ennotated . Thus, wT. tenax cells and subjected them to Illumina Hiseq2000 RNA-Seq analysis. 13.45 million sequence reads were mapped to the reference genome to obtain insights into the RNome of T. tenax. Subsequently, we searched the sequence reads for minimal conserved SRP RNA features. SRP RNA molecules are highly structured and contain several conserved structural features but only few absolutely conserved sequence segments. These sequences include a conserved SRP54 binding motif in helix 8b and a GNAR tetraloop motif connecting helix 6. We identified these short motifs in an intergenic region between the genes TTX_0683 (pyruvate phosphate dikinase [ppdK]) and TTX_0684 (protein phosphatase [ppa]). The prediction of RNA folding for this intergenic sequence revealed a high potential for extended helical regions, which prompted us to analyze this region in more detail. We utilized the obtained RNA-Seq reads to identify the 5'- and 3'-termini of a 309 nt long highly structured RNA transcript. The alignment of this RNA molecule with other archaeal SRP RNA molecules that are annotated in the SRP database (Thermoproteus species with ‘missing’ SRP RNA genes contain permuted SRP RNA sequences in which the transcripts’ termini have been shifted by over 100 nucleotides and the order of sequence motifs has been rearranged. We identified a similar permuted SRP RNA gene in T. uzoniensis and noticed that nucleic acid sequence variations do not occur in conserved regions of the SRP RNA and in most cases do not disrupt the structure of the SRP RNA (i.e. G-C base pairs are replaced by G-U or A-U basepairs)  . Sequenc-termini . The obs-termini . A TATA RNA gene . Northert probes . Full-let probes .10.7554/Escherichia coli and variant S-domains of the SRP RNA were transcribed in vitro  motif . A simil SRP RNA . BHB ele SRP RNA . A BHB c SRP RNA . The pre46 tRNAs . These i46 tRNAs . This fa46 tRNAs . We prodThermoproteus species and believe that this observation correlates with the emergence of increased tRNA gene fragmentation  were a kind gift of R. Hensel (Essen) and grown heterotrophically in Thermoproteus medium  and small RNAs (<200 nt), 0.1 g pelleted cells were lysed by homogenization and the RNA was subsequently isolated using the mirVanaTM miRNA Isolation Kit  according to the manufacturer’s instructions. To generate the SRP S-domain RNA constructs , two forward and reverse complementary DNA oligonucleotides with 15 bases overhangs were synthesized , 1 mM spermidine, 4 mM of ATP, CTP, GTP and UTP, 20 U RNase inhibitor and 1 µg T7 RNA polymerase at 37°C for 4 hr. The BHB substrate for RNA cleavage assays was synthesized  to ensure proper adapter ligation of RNA termini. The cDNA libraries were prepared according to the TruSeq Small RNA Library Protocol (Illumina) and sequenced using HiSeq2000 technology (Illumina) at the Max-Planck Genome Centre (Cologne). Sequencing data processing and analyses were performed using CLC Genomics Workbench 8 . The sequences were trimmed by quality score , adapter trimming and filtered by length (15 nt cutoff). The trimmed sequences were mapped to the T. tenax reference genome (FN869859) using default settings (mismatch cost set to 4). The T. tenax RNA-Seq data is available at Gene Expression Omnibus .Preparations of T. tenax total RNA was performed by electrophoretic separation on 8% denaturing-polyacrylamide gels next to an RNA and DNA marker . Additionally, to verify the circularization of SRP RNA, 15 ng of full-length SRP RNA in vitro transcript and circularized SRP RNA served as a running control. To obtain a circular SRP RNA control, full length SRP RNA transcript was 5'-dephosphorylated for 6 hr at 37°C using alkaline phosphatase (NEB) and the reaction was stopped by heating for 10 min at 65°C. Then, the RNA was 5'-phosphorylated using T4 PNK (NEB) and ATP for 1 hr at 37°C and ligated using T4 RNA ligase 1 (NEB) for 1 hr at 37°C. The reaction was stopped by incubation at 95°C for 5 min in 2× formamide loading buffer .Fractionation of 1–4 µg 32P]-ATP ) that were complementary to different regions in the SRP S-domain  and bands were visualized via UV irradiation. The RNA was blotted by capillary transfer onto nylon membranes  and immobilized by UV crosslinking. Hybridization was performed at 42°C for 18 hr in ULTRAhyb-Oligo buffer (Ambion) with two 5'-labeled probes (the label was added using T4 PNK [NEB] and γ-[T. tenax genes srp19 (TTX_2083) and srp54 (TTX_0615) were cloned into pET20b creating a fusion with a C-terminal 6× His-tag. The plasmids were transformed into E. coli strain DH5α (Invitrogen) and protein production carried out in E. coli Rosetta2(DE3)pLysS cells (Stratagene). Cultures were grown in LB medium at 37°C, shaking at 200 rpm. For protein production, 1 mM IPTG was added to a growing culture (OD600: 0.6) which was incubated for 3 hr. SRP19-His expression cells were homogenized in buffer 1 , lysed by sonication and cleared by centrifugation . The protein was heat-precipitated  and centrifuged . The SRP19-His protein was further purified by Ni-NTA affinity chromatography  and eluted with a linear imidazole gradient (0–500 mM) at 400 mM imidazole using a FPLC Äkta system . SRP54-His was purified by cell lysis in buffer 2 , lysed by sonication and cleared by centrifugation . The protein was loaded onto a Ni-NTA affinity chromatography column and eluted with a 500 mM imidazole step. Protein fractions were dialysed in buffer 3  and purified over a HiTrap Heparin Sepharose HP column  eluting with a linear salt gradient (0–1 M) at 650 mM NaCl.The The formation of SRP RNA-protein complexes was tested using a DEAE-Sepharose assay as described earlier . 2 µM ofT. tenax genes TTX_1594  and TTX_1893  were cloned together into pETDuet-1 and the protein was purified as described earlier and gel-purified as described above. 1–1000 nM purified splicing endonuclease was incubated with 2 nM of 5'-labeled RNA in nuclease buffer  at 60°C for 20 min. The cleavage reaction was stopped by adding formamide loading buffer and incubating at 95°C for 5 min. The reaction was loaded onto a 20% denaturing polyacrylamide gel running in 1× TBE, 6 W for 4 hr next to a low molecular weight marker  and an alkaline hydrolysis ladder of the BHB substrate. The cleavage products were visualized by phosphorimaging.10 pmol of the BHB substrate for RNA cleavage assays was 5'-labeled with T4 PNK (Ambion) and γ-[ review process). Similarly, the author response typically shows only responses to the major concerns raised by the reviewers.eLife posts the editorial decision letter and author response on a selection of the published articles . An edited version of the letter sent to the authors after peer review is shown, indicating the substantive concerns or comments; minor concerns are not usually shown. Reviewers have the opportunity to discuss the decision before the letter is sent  and two reviewers, one of whom is a member of our Board of Reviewing Editors.Thank you for submitting your work entitled "Circularization restores SRP RNA functionality" for consideration by The reviewers have discussed the reviews with one another and the Reviewing editor has drafted this decision to help you prepare a revised submission.Thermoproteus tenax and Thermoproteus uzoniensis are encoded in a permuted fashion and that the RNA ends are ligated to form a circular molecule, possibly to confer added stability to the RNA. The authors also show that a tRNA splicing endonuclease generates the site of circularization, pointing to a moonlighting activity for this enzyme. The reviewers only have limited comments:In this short report, Plagens et al. show that the SRP RNAs of 1) The title is vague and should mention the archaeal focus of the study.2) 3) While the sequencing data and co-migration with ligated RNAs in  In this short report, Plagens et al. show that the SRP RNAs of Thermoproteus tenax and Thermoproteus uzoniensis are encoded in a permuted fashion and that the RNA ends are ligated to form a circular molecule, possibly to confer added stability to the RNA. The authors also show that a tRNA splicing endonuclease generates the site of circularization, pointing to a moonlighting activity for this enzyme. The reviewers only have limited comments:1) The title is vague and should mention the archaeal focus of the study.Thermoproteus” was added.We changed the title. SRP is spelt out in full and “…in 2) Thermoproteus species . We provide additional support with a new figure supplement  While the sequencing data and co-migration with ligated RNAs in We performed Northern blot assays with RNase R treated total RNA (1-20U RNase R/μg RNA) and saw no significant reduction of the signal. However, RNase R resistance might also be observed for the highly structured linear SRP RNA with its four nucleotide 3’ overhang as it was shown that “duplex RNAs with no overhang or with a 4-nucleotide overhang bind extremely poorly to RNase R and are inactive as substrates”. . We sequenced the termini ligation site in hundreds of unique reads in independent RNA-Seq datasets (available at GEO database GSE72127) and consider this to be conclusive evidence.


This allows sensitive magnetic field control of the 13C nuclear spin polarization for NMR applications and significant suppression of the 13C nuclear spin noise to prolong the NV spin coherence time.Enhancing the polarization of nuclear spins surrounding the nitrogen-vacancy (NV) center in diamond has recently attracted widespread attention due to its various applications. Here we present an analytical formula that not only provides a clear physical picture for the recently observed polarization reversal of  The atomic nuclear spins are central elements for NMR and magnetic resonance imagingon-site15N (or 14N) and the strongly coupled13C nuclei in the first shell of the vacancy6202122An exception is the nitrogen-vacancy (NV) center57910101314156171819202152325271725et al.13C nuclei and observed multiple reversals of the polarization direction over a narrow range (a few mT) of magnetic field. This interesting observation allows sensitive control of the polarization of strongly coupled13C nuclei by tuning the magnetic field, but a clear physical picture remains absent. Furthermore, in most of the existing works, only a few strongly coupled nuclear spins  over a narrow range (a few mT) of magnetic fieldweakly coupled13C nuclei (with HFI down to ~kHz) and (ii) control the direction of their polarization by tuning the magnetic field over a much narrower range (~0.1 mT). First, we introduce an intuitive physical picture for our strategy. Then we present an analytical formula that substantiates this physical picture. Finally, we perform numerical simulations that demonstrate our strategy for a few hundred weakly coupled 13C nuclei.Motivated by the experimental observation of Wang B along the N-V axis (z axis), the electron Zeeman splitting Our model consists of a negatively charged NV center coupled to many surrounding nuclear spins at ambient temperature. The NV center has a ground state triplet 13C nuclear spin-1/2 and drop the nuclear spin index i. Since Β as a constant independent of the magnetic field B. The different energy mismatches make it possible to selectively drive one transition into resonance while keeping the other transition off resonance: set the magnetic field to R) of the NV ground state as a crucial ingredient for achieving strong nuclear polarization: B− (B+). The direction of the polarization can be reversed by switching the magnetic field between B− and B+. For first-shell 13C nuclei, 13C nuclei, Now we provide an intuitive physical picture for using an optically pumped NV center near the GSLAC to strongly polarize the nuclear spins and control their polarization direction by the magnetic field. For brevity we focus on one Under optical pumping, seven energy levels of the NV center are relevant . The NV-where τc of the NV center is much shorter than the timescale of the DNP process, because in this case the NV center can be regarded as a non-equilibrium Markovian bath. Applying this theory to a 13C nuclear spin-1/2, we obtain the rate equation W+(W−) is the rate of the nuclear spin raising (lowering) transition, as discussed in the previous subsection. The real-time evolution of the nuclear spin polarization Our work is based on a recently developed microscopic theory3031For weak optical pumping far from saturation, we can derive (see Methods) the following Fermi golden rule for the nuclear spin transition rates:R is equal to the optical pumping rate, i.e., the number of optical transitions per unit time from the NV ground orbital to the excited orbital (see Methods). This optically induced level broadening is typically much larger than the intrinsic NV spin decoherence rate (~1 kHz) and provides a microscopic explanation for the previously observed NV level broadening under laser illumination23B− (B+), so that the rate W− (W+) of the nuclear spin lowering (raising) transition is resonantly enhanced, while the rate W+ (W−) of the nuclear spin raising (lowering) transition is suppressed. The relation pss depends strongly on the HFI tensor A, e.g., for the 15N nucleus with where W calculated from Eq. R is so small or the HFI is so strong that the DNP time calculated from Eq. τc, the NV center becomes a non-Markovian bath and Eq. τc, the true DNP time would be lower bounded by ~τc. This can be easily understood: since the nuclear spin dissipation originates from the dissipation of the optically pumped NV center, the timescale τc of the NV center dissipation.Equation 13C located at 3Å away from the NV center, the dipolar HFI gives a nuclear spin relaxation time >1 s. These effects are described by nuclear depolarization W by Up to now, we have neglected other nuclear spin relaxation mechanisms, such as spin-lattice relaxation and HFI with NV excited states. The former occurs on the time scale ranging from a few seconds to tens of minutes1713C nuclei, where 13C nuclei, where γ = 13 MHzBelow we first specialize to strongly coupled ture cf. : excitedstrongly coupled13C nucleus in the first shell of the NV center under optical pumping near the 13C nuclear polarization over a narrow range (~a few mT) of magnetic fields. This interesting observation allows sensitive control of the polarization of the strongly coupled 13C nuclei by tuning the magnetic field, but a clear physical picture remains absent. Here the very strong HFI makes the DNP time calculated from Eq. 13C mixing, the 13C nuclear polarization depends weakly on the optical pumping up to To begin with, we consider the DNP of a B− originates from the dominance of the raising transition rate et al.13C mixed levels, so the uncertainty of this estimate is relatively large, e.g., the estimates based on different transitions give different results, denoted by the circles and squares in In 13C nucleus13C nuclei, our analytical formula becomes accurate. To demonstrate this point, we keep B± , the DNP rate calculated from Eq. −1. Away from B±, our analytical DNP rate For the first-shell B+ (B−) approaches +100% (−100%) due to the resonance of the nuclear spin raising (lowering) transition. This indicates the possibility of achieving strong positive (negative) nuclear polarization for weakly coupled nuclear spins by tuning the magnetic field to B+ (B−). In the above calculations, we have assumed perfect optical initialization of the NV center into B± only decreases sublinearly with increasing initialization error, e.g., the nuclear polarization remains slightly above 80% when the optical initialization fidelity decrease to 80%. Since the nuclear polarization is not so sensitive to the NV optical initialization fidelity, hereafter we always assume perfect optical initialization of the NV center.An important feature in 13C nuclei with weak HFI B+ and B− is B+ or B−, the experimental control precision δB of the magnetic field should be smaller than 0.08 mT. This is accessible by current experimental techniques, e.g., −1, this requires the HFI to be larger than 1 kHz. Hereafter we assume that this condition is satisfied. The intuitive physical picture suggests that the linewidth R  of the NV ground state is essential, so we divide our following discussion into strong optical pumping and weak optical pumping, respectively.Now based on the analytical formula in Eq. B± are not spectrally resolved. In this case, the nuclear polarization is uniquely determined by the HFI tensor A. For dipolar HFI,Under strong optical pumping θ of the 13C location R through is uniquely determined by the polar angle B+ (B−). For example, in B+ (marked by white dotted lines) and the resonance peak of the lowering transition at B− (marked by black dotted lines) are clearly resolved. Correspondingly, in B+ (B−), superimposed on the usual dependence on the polar angle θ via 13C nucleus located at −1, sufficient to overcome the slow nuclear depolarization −1.The most interesting case is weak optical pumping 13C DNP, now we generalize the above results to many 13C nuclear spins coupled to the NV center via exactly) and treat the transverse HFI with second-order perturbation theory, whereHaving established a complete picture for single-is the collective Overhauser field from all the nuclei.ith nucleus) produces an Overhauser field hm. This renormalizes the ith nucleus conditioned on the many-nuclei state being A, B with Ai, The physical picture of the many-nuclei DNP is as follows. Up to leading order, the flip of different nuclei by the transverse HFI is independent, in the sense that at a given moment, only one nuclear spin is being flipped, while other nuclear spins simply act as “ spectators”. However, the flip of each individual nuclear spin does depend on the states of all the nuclear spins via the collective Overhauser field The above physical picture is quantified by the following rate equations for the diagonal elements ith nucleus changes from 13C nuclei gives a typical Overhauser field 13C nucleus at 2 nm away from the NV center is reduced to −1. Therefore, under weak pumping which has been derived by adiabatically decoupling the fast electron dynamics from the slow DNP process3031NP rate   for a 13N nuclear spin-1/2’s, the number of variables N. When N is small, we can solve Eq. N, however, the exponentially growing complexity prohibit an exact solution to Eq. For N = 7) of randomly chosen 13C nuclei coupled to the NV via dipolar HFI, the average polarization N = 400 randomly chosen 13C nuclei, the exact solution is no longer available and we plot the approximation results in B− arises from the dependence θ of the nuclear spin location: more nuclear spins have 13C nuclear spins by using weak optical pumping near B±. The polarization of these weakly coupled 13C nuclei is ultimately limited by nuclear depolarization, which becomes significant when the HFI becomes too weak. This can be clearly seen in the spatial distribution of the nuclear polarization near B+ [B− [B+, strong positive polarization is achieved for 13C nuclei with 13C nuclei, the HFI strength is too weak for the DNP to dominate over the nuclear depolarization, so their polarization drops significantly. Similarly, near B−, strong negative polarization can be achieved for 13C nuclei with As shown in  near B+  and B− [r B+ [B− . Near B+15N or 14N nucleus has an isotropic transverse HFI and hence 13C nuclei, except for a shift of the 14N) or ~3 MHz (for 15N), corresponding to a shift of the resonance magnetic field by ~0.78 G (for 14N) or ~1.1 G (for 15N).Finally, we recall that the on-site 13C nuclei, but also reveals an efficient scheme to strongly polarize weakly coupled 13C nuclear spins ~25 Å away from the NV center (HFI strength ~1 kHz) by tuning the magnetic field under weak optical pumping. These results provide a clear guidance for optimizing future dynamic nuclear polarization experiments. For example, this scheme could be used to polarize distant 13C nuclei in isotope purified diamond13C nuclear spins.In conclusion, we have presented a comprehensive theoretical understanding on the dynamic nuclear polarization induced by an optically pumped NV center near the ground state anticrossing at ambient temperature. Our results not only provide a clearly physical picture for a recently observedI on its Zeeman sublevels According to the theory3031tranvserse HFI exactly), the transition rate from Up to second order of the where Since we consider the NV center near the GSLAC, we can exclude the energy levels where where Now we calculate which gives four coupled equationsHere and from which we obtain the solutioncomplex self-energy corrections to where For simplification, we use the fact that the NV excited state dephasing For spin-1/2, Eq. N-nuclei density matrix ith nuclear spin state N single-spin polarizations ith nucleus give N coupled equations:The essential idea of the mean-field approximation is to assume small inter-spin correlation, so that the ith nucleus averaged over the states of all the other where N coupled differential equations for N coupled nonlinear equations with recursive methods.i.e., How to cite this article: Wang, P. et al. Strongly polarizing weakly coupled 13C nuclear spins with optically pumped nitrogen-vacancy center. Sci. Rep.5, 15847; doi: 10.1038/srep15847 (2015).


The salient features of heat transfer coefficient Z and trapping are also discussed for various parameters of interest including magnetic field, curvature, material parameters of fluid, Brinkman, Biot and compliant wall properties. Main observations of present communication have been included in the conclusion section.Here peristaltic activity for flow of a Prandtl-Eyring material is modeled and analyzed for curved geometry. Heat transfer analysis is studied using more generalized convective conditions. The channel walls satisfy complaint walls properties. Viscous dissipation in the thermal equation accounted. Unlike the previous studies is for uniform magnetic field on this topic, the radial applied magnetic field has been utilized in the problems development. Solutions for stream function ( Peristaltic transport holds a considerable position in physiology and engineering. Extensive research has been addressed under different situations since the seminal works of Latham  and ShapAll the aforementioned attempts and existing information on this topic witness that much attention has been given to the flows with peristalsis in a planer channel which seems inadequate in reality. It is because of the fact that most of the ducts in physiological and industrial applications are curved. Influence curvature on peristaltic transport liquid is discussed in only some studies. Sato et al.  initiallThe facts of present attempt is to advance the theory of peristalsis of non-Newtonian materials via three important aspects i.e. curved channel, convective heat transfer condition and radial magnetic field. Hence we model here the governing flow problem employing constitutive relations of Prandtl-Eyring fluid. The flow formulation is completed through compliant properties of channel walls. Arising nonlinear analysis is computed for the series solutions. Arrangement of paper is as follows. Next section formulates the problems for flow and temperature. Section three includes solution expressions for the stream function, temperature and heat transfer coefficient. Discussion to graph of different physical quantities for various parameters is assigned in section four. section five consists of conclusions.d1 looped in a circle with radius R* and center O  the components of extra stress tensor, Cp denotes the specific heat, ρ the density, κ stands for thermal conductivity and T the temperature of fluid.The wave form at the walls are(S) for Prandtl-Eyring fluid is written as:L = (grad V) and A/C are material constants of Prandtl-Eyring fluid model.Extra stress tensor The boundary conditions have been assumed in the formT0 is the temperature at both upper and lower walls of the channel, h1 the heat transfer coefficient at upper/lower walls whereas Sxx, Srr, Srx and Sxr are the elements of S. Moreoverm1, τ and d are the mass per unit area, longitudinal tension and the viscous damping coefficient respectively. HavingHere Eqs ψ  byTaking the stream function ϵ (= a/d1), δ (= d1/λ) and K represent the dimensionless amplitude ratio, wave number and curvature parameter respectively. (= cd1/ν) depicts the Reynolds number, Pr (= μCp/κ) the Prandtl number, We (= mc/d1) the Weissenberg number, Ec (= c2/CpT0) the Eckert number, Br (= EcPr) the Brinkman number and Bi1(= h1/d) the Biot number. Further the dimensionless form of extra stress tensor after invoking long wavelength and low Reynolds number approximation becomesβ is used to find the solution. Thus we expand ψ, Srx, θ and Z as follows:The governing equations are highly non-linear and exact solution seems impossible. Therefore, perturbation method for small parameter β0 we haveUsing eqs Solving the above system we getThe results corresponding to first order system are1 → C6 and B1 → B12 can be evaluated using MATHEMATICA.Here the algebraic values of Cu), temperature distribution (θ), heat transfer coefficient (Z) and stream function (ψ).This portion analyzes the impact of several parameters of interest on the velocity  is increasing function of Bi1 (In Figs d β Figs  and 17. n of Bi1 .H on streamlines. Decrease in the size is noticed for increased H. k on the streamlines. These figures show that the bolus size enhances for larger K. α is enhanced. Number of streamlines are more. β. We have analyzed through E1 and E2 while increase in E3 has no show significant effect. Moreover, by taking α = β = H = Bi1= 0 results can be obtained for viscous case [Figs –25 displous case .Peristaltic motion of MHD Prandtl Eyring fluid flowing through curved geometry is discussed. Walls of channel are chosen to be compliant. Heat transfer phenomenon is also analyzed. Main findings of this study are:Symmetry of velocity profile about the centre line is disturbed for the flow in curved channel.H.The velocity profile has decreasing behavior for increasing values of Hartman number Bi1.Temperature profile is a decreasing function of Biot number The absolute value of heat transfer coefficient for planer channel is higher than the curved one.β.Size of trapped bolus increases for α but it decreases via


We have developed a graphics processor unit (GPU-) based high-speed fully3D system for diffuse optical tomography (DOT). The reduction in executiontime of 3D DOT algorithm, a severelyill-posed problem, is made possible through the use of (1) an algorithmic improvement that uses Broydenapproach for updating the Jacobian matrix and thereby updating the parameter matrix and (2) the multinodemultithreaded GPUand CUDA (Compute Unified Device Architecture) softwarearchitecture. Two different GPU implementations of DOT programs are developed in this study:(1) conventional C language program augmented by GPU CUDA and CULAroutines (C GPU), (2)MATLAB program supported by MATLAB parallel computing toolkit for GPU (MATLAB GPU).The computation time of thealgorithm on host CPU and the GPU system is presented for C andMatlab implementations.The forward computation uses finite element method (FEM) andthe problem domain is discretized into 14610, 30823, and 66514 tetrahedralelements.The reconstruction time, so achieved for one iteration of the DOTreconstruction for 14610 elements, is0.52 seconds for a C based GPU program for 2-plane measurements. The corresponding MATLAB based GPU program took 0.86 seconds. The maximum number ofreconstructed frames so achieved is2 frames per second. The numerical methods used for discretizing the diffusion equation are the finite difference method (FDM)  –6. The c  is very  –10. The  –10. Sinc . The DOT  or deter  or a sim . The RTE , 15–17.  . Therefo , 20, of od (FDM) , 22, andμ0 = μguess) Jacobian is calculated only once and thereafter, in each iteration, Jacobian is updated using rank-1 update. The forward model is solved for model predicted flux [MC = F(μi)]. The difference between predicted measurement and the experimental measurement [ΔM = ME − MC] is used for updating the Jacobian [Ji+1 = Ji + ΔJi] , and μa and μs′ are absorption coefficient and reduced scattering coefficient, respectively. The diffusion equation is valid only when μs′ ≫ μa, which is true for most of the biological tissues in the near-infrared region. The input photon is from a source of constant intensity (Adc), modulated by a sinusoidal current of amplitude Aac and frequency ω0 located at r = r0. The transmitted output optical signal is of the form Adc + Aaccos(ω0t + ϕ) and we measure amplitude and phase by lock-in detection method.The time independent diffusion equation (DE) for the light transport given as –6(1)−∇·The boundary condition (Robin boundary condition) is given byF. M is the measurement vector obtained from ΦδΩ|:predicted = ℳ[Φ]) on the surface boundary (Ω). Due to spatial  variation of optical parameter (Δμi(r)), the perturbation equation in terms of optical parameter can be written in Taylor series expansion, retaining only first derivative asF′) is Jacobian matrix  is computed through analytical method. Since Broyden's method avoids direct computation of Jacobian, this approach provides a computationally simple algorithm [The Broyden Jacobian update equation is given as (7)Ji+1=Equation  is referlgorithm , 41.ϕ. The forward light transport equation DE is discretized using FEM. One of the simplest approximations of ϕ is a continuous piecewise linear function bi(r); that is, V over which the function ϕ is defined is divided into a finite set of disjoint elements. The basis functions bi(r) have only limited support, limited to a particular element, and are in turn made up of shape functions which are piecewise linear.In the forward equation , one seeRl over all nodal points with the same basis functions vanishes over V. Here the residual isIn the so-called Galerkin method , 5, 17, valuated . The amoTo find the properties of the overall system, we must combine the matrix equations of each tetrahedral element in such a way that the resulting matrix represents the behavior of the entire solution region of the problem. The boundary conditions must be incorporated after the assemblage of the individual element contributions.K, C, and F are sparse matrices whose elements are given by  and absorption coefficient μa(r). K has a dimension Nn × Nn, where Nn is the number of nodes and is highly sparse, generally with a banded structure. Q is the forcing term.The discretized, weak form of  is evalugiven by . K is thμa = 0.01 mm−1 and μs′ = 1.0 mm−1, respectively. Two absorbing inhomogeneities of different geometries and contrasts were embedded inside the homogeneous phantom . ϕs is solved using ϕs = K−1 · Q.It computes JT · J + λ · I)Δμ = JT · ΔM is assembled and solved for Δμ.The equation ,C CUDA code to utilize GPU (C GPU),MATLAB serial code to execute in host CPU (MATLAB CPU),MATLAB single/double precession GPU code (MATLAB GPU).We developed 4 types of codes for Broyden based DOT reconstruction algorithm. They areμaactual and the estimated μa are shown in Figures We reconstructed 3D images of the simulation and experimental phantoms  using boIn order to verify the stability of the algorithm, we have reconstructed images from noisy measurement data. White Gaussian noise (WGN) of 2% was added to the measurement data . The croThe main focus of the study is to evaluate the performance of the GPU implementations (both C and MATLAB). The Jacobian computation time for conventional and Broyden based methods on C CPU, C GPU, MATLAB CPU, and MATLAB GPU platforms for mesh sizes (a) 14610, (b) 30823, and (c) 66514 elements is presented in Figures The memory size available on GPU board (5 GB) puts an upper limit on the mesh size that can be implemented. The current study uses only full matrix computation. For a higher mesh size, we need to resort to sparse matrix computations that will ease the memory requirements. A few studies have been reported using sparse matrix computation because of the sheer size of the problem , 35. FreThe development of MATLAB based GPU application opens up large opportunities. It has many advantages which include (1) faster development of applications because MATLAB has a rich collection of libraries and functions and (2) much easier development of application program in MATLAB compared to that using conventional C based programming language.We have developed an efficient, GPU-based fully 3D tomographic system for diffuse optical tomography (DOT). The 3D DOT, a severely ill-posed and ill-conditioned problem, is solved by making use of the recently proposed Broyden approach for updating the Jacobian matrix, which has computational complexity orders of magnitude lower compared to conventional Jacobian update strategy. The GPU acceleration of the algorithm resulted in a reconstruction speed of 2 frames/second.