A small effect of time , and a medium interaction between age and time  was observed. (4) Conclusions: This study demonstrates both young and older adults recover PPO following 3 and 5 days’ rest. As such, both groups could undertake SIT following three days of rest, without a reduction in PPO.(1) Background: High-intensity interval training (HIIT) exerts effects indicative of improved health in young and older populations. However, prescribing analogous training programmes is inappropriate, as recovery from HIIT is different between young and older individuals. Sprint interval training (SIT) is a derivative of HIIT but with shorter, maximal effort intervals. Prior to prescribing this mode of training, it is imperative to understand the recovery period to prevent residual fatigue affecting subsequent adaptations. (2) Methods: Nine older  and nine young  participants performed a baseline peak power output (PPO) test. Subsequently, two SIT sessions consisting of three repetitions of 20 s ‘all-out’ stationary cycling bouts interspersed by 3 minutes of self-paced recovery were performed. SIT sessions were followed by 3 days’ rest and 5 days’ rest on two separate occasions, in a randomised crossover design. PPO was measured again to determine whether recovery had been achieved after 3 days or after 5 days. (3) Results: Two-way repeated measure  × 3 time ) ANOVA revealed a large effect of age ( High-intensity interval training (HIIT) is characterised by exercise above 80% of maximum heart rate interspersed with lower-intensity recovery phases . Sprint A limitation of HIIT is that it generally requires intensity-based calculations ,10,11, wDelayed recovery seen in older adults compared to their younger counterparts could be attributed to several biological processes . The driSIT has demonstrated positive power adaptations in young cohorts ,30,31,32a priori that for PPO restoration, older participants would require 5 days’ recovery, and young individuals would recover after 3 days.The previously discussed literature justifies the investigation of a low-volume SIT protocol as an intervention to increase overall physical function in older adults. However, before the adaptations to a 3 × 20 s ‘all-out’ SIT exercise training programme can be explored in older adults, it is imperative to know the duration of rest sufficient for post-training PPO recovery. A previous review has discussed literature on HIIT intersession recovery, concluding optimal recovery to be approximately 48 h following HIIT . HoweverThis study was carried out in accordance with the Declaration of Helsinki and approved by the University of Cumbria Research Ethics Committee (Reference code: 16/74). Written informed consent was obtained from all participants prior to study commencement. A Physical Activity Readiness Questionnaire (PAR-Q) and American College of Sports Medicine (ACSM) pre-exercise participation screening were completed . ParticiOn the first visit, a baseline PPO assessment was completed. Seven to ten days later, participants performed a SIT session. This exercise was followed by 3 days’ rest or 5 days’ rest in a randomised crossover design, after which they returned to complete a second PPO measure. Subsequently, participants returned 7–10 days later to complete the other arm of the study .Following measurement of stature and body mass, participants mounted the cycle ergometer, which was set up according to manufacturer's guidelines . Subsequently, participants warmed up for 6 minutes at approximately 70 W, interspersed with three ~2 s maximal sprints with an air brake resistance of 8 and a magnetic resistance of 1. Following 5 minutes of passive recovery, participants performed a 6 s Herbert test , which iAs above, participants warmed up for 6 minutes at approximately 70 W, interspersed with three ~2 s maximal sprints with an air brake resistance of 8 and a magnetic resistance of 1. Following 5 minutes of passive recovery, participants remounted the ergometer with the air brake resistance set to 3 and magnetic resistance set to 1. Participants completed 3 × 20 s maximal sprints, interspersed with 3 minutes of active recovery, with strong verbal encouragement during each sprint . A summap < 0.05. Partial eta squared (2pn) was used as a measure of main effect, defined as small 0.02, medium 0.13, and large 0.26. Cohen's d was calculated for pairwise comparisons Additionally, an independent samples t-test was conducted to compare weekly mean habitual physical activity at above moderate intensity between older and young participants. Effect size was determined using Cohen’s d, defined as small 0.1, medium 0.3, and large 0.5. Data are presented as means ± standard deviation (SD). Statistics were processed using SPSS version 23.0 (IBM). Following a Shapiro–Wilk’s test of normality and Levene's test for homogeneity of variance, a two-way repeated measures ANOVA (age (young vs. older) × recovery time ) was conducted. Alpha level was set a priori at p = 0.002, 2pn = 0.460), small time effect , and medium interaction effect  was present for PPO. Younger participants produced greater PPO than older participants . Older PPO for baseline, 3 days’ rest, and 5 days’ rest was 543 ± 151 W, 561 ± 152 W, and 555 ± 152 W, respectively . Weekly mean habitual physical activity revealed a large effect between older (417 ± 313 minutes) and young participants  1.01, p = 0.342, d = 0.68); equal variances were not assumed (p = 0.14).A large age effect , maintained for 30 s used by Herbert et al. . Given tExcessive production of reactive oxygen species has been implicated in deleterious effects via inflammatory pathways to muscle function and performance . AlthougStrength training studies in older adults demonstrate two or three sessions per week are optimal to facilitate adaptions ,46,47. SHigher-frequency HIIT in older adults with a mean age of 63 years performed thrice weekly has increased peak oxygen uptake by 3% and 7% for women and men, respectively, over 6 weeks , approxiPrevious research by Adamson et al.  demonstrWe acknowledge the present study is not without limitations. For example, the use of recreationally active older adults was used in the current investigation, which does not permit application of these results to sedentary older adults. However, this recruitment strategy was necessary to ensure safe participation of older participants during maximal exercise . Yet, HIIn conclusion, the results of this study suggest that PPO recovery is similar between older and young adults after 3 days’ rest following SIT. These data permit SIT prescription in older adults, in the indicative knowledge that recreationally active individuals will be recovered after 3 days’ rest. We believe these data can guide prescription of SIT in healthy and active older individuals who may perform SIT following 3 days’ rest. As a strength of SIT over HIIT is that prescription is uncomplicated, future research may consider ecologically applicable modes of SIT in older adults, and whether SIT is a viable intervention to improve physical functioning.


Plasmodium vivax guanylate kinase (PvGK), a potential drug target against malaria, was determined. The relative concentrations of the two substrates (GMP and ATP) have a distinct effect on reaction velocity. Kinetic analyses showed the PvGK-catalyzed reaction to be associated with atypical kinetics, where substrate inhibition kinetics and non-Michaelis-Menten  kinetics were found with respect to GMP and ATP, respectively. Additionally, the method was used in inhibition assays to screen twenty fragment-like compounds. The assays were robust and reproducible, with a signal window of 3.8 and a Z’ factor of 0.6. For the best inhibitor, an IC50 curve was generated.The development of a high-performance liquid chromatography (HPLC)-based method, for guanosine monophosphate kinase activity assays, is presented. The method uses the intrinsic UV absorption (at 260 nm) of substrates and products of the enzymatic reaction  to unambiguously determine percent conversion of substrate into product. It uses a commercially available C18 column which can separate reaction samples by elution under isocratic conditions in 12 min per run. The kinetics of the forward reaction catalyzed by   •Simple HPLC separation of nucleotides involved in the guanylate kinase reaction.•Direct and unambiguous determination of percent conversion of substrate into product.•Plasmodium vivax guanylate kinase (PvGK) activity studies.Successful application to •PvGK found to be associated with atypical kinetics.Reaction catalyzed by •Robust and reproducible inhibition assay for compound screening. GTP/dGTP, in turn, can be used for nucleic acid or cyclic GMP (cGMP) synthesis. Due to its role in supplying DNA and RNA precursors, guanylate kinase constitutes a potential antimicrobial drug target ,2. In ma.7.4.8, cPlasmodium vivax (P. vivax) is the malaria parasite with the widest geographical distribution and is responsible for about half the cases of malaria outside Africa  cells transformed with the BG1861 (a pET14b derivative) vector expressing full-length PvGK with an N-terminal hexa-histidine tag were kindly provided by Wesley C. Van Voorhis and Gregory J. Crowther, from the University of Washington. As previously described ) × H), where [I] is the inhibitor concentration and H the Hill Slope.The inhibition assays were performed at room temperature for 20 min. Fragment stock solutions were prepared in dimethyl sulfoxide (DMSO) at 250, 125 or 5 mM and assayed at 5 mM, 2.5 mM or 100 μM final concentrations, respectively. Final DMSO percentage in the enzymatic assay was 2% (v/v). Percent inhibition was calculated using the following equation: 33.12PO4/K2HPO4), run isocratically with 3–5% methanol (v/v), were tested  + [GDP]) of 100 μM, demonstrated good intraday accuracy and precision of the method . Percent3.2PvGK was successfully achieved in E. coli by auto-induction with 48 h incubation time. The subsequent purification involved just two separation steps: immobilized metal-ion affinity chromatography with a Ni2+-NTA column and anion-exchange chromatography with Q-Sepharose. A representative SDS-PAGE is shown in Large-scale expression of To determine the ideal quencher for the enzymatic reaction , addition of 50 μL of MeOH, 10 μL HCl 32% (v/v), 10 μL EDTA 250 mM and 10 μL HCl 0.1% (v/v), were investigated. Quenching with 10 μL HCl 0.1% (v/v) was found to be the best method. Under these conditions, the pH of the reaction mixture was decreased to 3, which was sufficient to denature the enzyme, but did not interfere with retention time and peak shape of the HPLC separation.PvGK concentrations , three corresponding different incubation times  and fixed GMP and ATP substrate concentrations (100 μM). If the enzyme is stable during the course of the enzymatic reaction, for constant concentrations of substrate and any activator or inhibitor, the amount of product formed depends only on the concentration of enzyme and the reaction time h/(Kprime+ [S]h). An apparent Kprime  of 15.6 ± 2.07 μM was obtained for ATP. Apparent Vmax was estimated as 0.74 ± 0.06 μM/min.Interestingly, the ATP saturation curve was sigmoidal  before the addition of ATP for reaction start. These controls were pooled together and used to evaluate the assay performance and reproducibility over the course of the experiments. With a total of 81 0% and 100% inhibition controls, a signal window of 3.8 and a Z′ factor of 0.6 were obtained. Since a signal window >2 is generally recommended and a Z’ factor >0.5 is considered very good [Twenty fragment-like compounds that emerged from a native mass spectrometry-based binding screening against e tested . Based oery good , the sui1,PvGK activity via a non-specific mechanism involving chelation of Mg2+, which is essential for enzymatic activity. In agreement with our results, Kandeel et al. found that EDTA inhibited P. falciparum GK by 85% at 3 mM [in vitro and in vivo [2 inhibited PvGK activity by 100% at 5 mM and an IC50 curve was generated -Huperzine A, was found to be an activator. (−)-Huperzine A is a reversible acetylcholinesterase inhibitor and has been investigated for the treatment of Alzheimer's disease [Percent inhibition for each tested fragment was calculated based on 0% and 100% inhibition controls assayed on the same day. Alongside the fragment-like compounds, EDTA and a known broad-spectrum kinase inhibitor with fragment-like physicochemical properties, 7,8-dihydroxycoumarin (daphnetin) 1,a, were t at 3 mM . Daphnet at 3 mM  and poss in vivo . Seven oenerated b. The de disease .Fig. 7Ch4Guanylate kinase activity is often measured using coupled-enzyme systems and/or fluorescent/luminescent probes. Herein, we described the development of an HPLC-based method specific for guanylate kinase activity, which employs direct detection of substrates and products of the enzymatic reaction  through their intrinsic UV absorption at 260 nm. Chromatographic separation was achieved in 12 min per run with a C18 column operating under isocratic conditions. Within the range of substrate concentrations used, unambiguous determination of the conversion of substrate into product could be achieved using GMP and GDP integrated chromatogram peak areas. Under the experimental conditions described, the method demonstrated good accuracy and precision.PvGK, a potential drug target against malaria. This protein is a soluble, cytosolic regulatory enzyme highly expressed during the liver stage of Plasmodium life cycle. Enzyme kinetic analyses revealed that the activity of PvGK depends highly on the relative concentrations of the two substrates GMP and ATP. In addition to enzyme kinetic studies, the present method demonstrated to be suitable for compound screening. Twenty fragment-like compounds were tested in inhibition assays and an IC50 curve was generated for the best PvGK inhibitor, compound 2.The method was successfully applied to study the activity of


GE) dysfunction in “Chao2‐10” rice. Here, we compared the antihypertensive effects of “Chao2‐10” brown rice (C2‐10), “Shangshida NO.5” brown rice (GER), and pre‐germinated “Shangshida NO.5” brown rice (PGER) in spontaneously hypertensive rats (SHR). Male SHR at 6 weeks of age were divided into four groups and were fed with (a) a control diet (control), (b) a 40% C2‐10‐supplemented diet (C2‐10), (c) a 40% GER‐supplemented diet (GER), or (d) a 40% PGER‐supplemented diet (PGER) for 8 weeks, and their physiological and biochemical parameters were measured. The results showed that the C2‐10‐, GER‐, and PGER‐supplemented diets significantly decreased systolic blood pressure (SBP) and diastolic blood pressure (DBP) during the experiment. At the end of the experimental period, the SBP and DBP of the C2‐10, GER, and PGER groups were 7.6, 23.3, and 31.1 mmHg and 9.8, 21.1, and 29 mmHg lower than those in the control group, respectively, suggesting the GER and PGER diets were better able to inhibit blood pressure elevation than the C2‐10 diet. The serum creatinine levels in the C2‐10, GER, and PGER groups and the blood urea nitrogen content in the PGER group were significantly lower than those of the control group, indicating that C2‐10‐, GER‐, and especially PGER‐supplemented diets improved renal function. In addition, the antioxidant activity of the C2‐10 group and especially of the GER and PGER groups also improved. The above results suggest that “Shangshida NO.5” rice, particularly pre‐germinated rice, is a good dietary supplement for preventing the development of hypertension.“Shangshida NO.5” is a giant embryo mutant resulting from giant embryo gene ( Hypertension can be caused by several factors, such as genetics, environment, diet, and lifestyle, and several types of medicines, including diuretics, β‐adrenoceptor blockers, angiotensin‐converting enzyme (ACE) inhibitors, calcium channel blockers, α‐adrenergic receptor blockers, vasodilators, and centrally acting drugs, can be used to treat hypertension , one of the major inhibitory neurotransmitters in the central nervous system , an embryo (2%–3%), and an endosperm (approximately 90%) : control diet (control), “Chao2‐10” brown rice diet (C2‐10), “Shangshida NO.5” giant embryo brown rice diet (GER), and pre‐germinated “Shangshida NO.5” giant embryo brown rice diet (PGER). The compositions of the experimental diets are shown in Table Six‐week‐old male spontaneously hypertensive rats (SHR) were used in this study. The forty SHR were divided into four groups n = 0: contro2.2The systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate were measured in unanesthetized animals using the tail‐cuff method with a BP‐2006A automated noninvasive blood pressure meter (Softron Co.). Each of these parameters was measured three to five times for each animal, and the mean of at least three readings was regarded as the value of each parameter for the animal. To raise the body temperature of the animal, the animal was placed in a heated box (38°C) for approximately 10–15 min before measurement.2.3g at 4°C for 10 min. The livers were promptly excised and washed with 1*PBS sodium. Both the plasma and kidney tissue samples were stored at −80°C until analysis.At the end of the treatment, the animals were anesthetized with chloral hydrate sodium (1 ml/100 g body weight), and blood samples were obtained from the abdominal aorta and transferred to centrifuge tubes with EDTA. All tubes were centrifuged at 7,700 2.4The blood urea nitrogen (BUN), serum creatinine (SCR), norepinephrine (NE), rennin, aldosterone (ALD), angiotensin II (Ang II), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), total antioxidant capacity (T‐AOC), total cholesterol (TC), and triacylglycerol (TG) levels were determined. Kidney SOD, CAT, MDA, and T‐AOC levels were also determined. BUN was detected by urease methods, SCR by picric acid methods, SOD by xanthine oxidase, MDA by thiobarbituric acid, and CAT and T‐AOC by colorimetric methods using commercially available kits (Nanjing Jiancheng). NE, rennin, ALD, and Ang II were measured with an ELISA immunoassay kit (Nanjing Jiancheng). All tests were performed according to the manufacturer's instructions.2.5p < .05 and p < .01 were considered significant at 95% and 99% confidence intervals, respectively.Values are presented as the means ± standard errors. To evaluate the differences among the groups studied, one‐way ANOVA followed by the LSD test was used. Probability values of 33.1In this study, the body weights of the four groups of SHR fed with different supplemented diets were similar during the experimental period Table . However3.2To understand the effects of supplemented diets on plasma levels of parameters related to the GABA hypotension pathway, we assayed the levels of the related parameters, including NE, rennin, Ang II, and ALD Table . We foun3.3In this study, we also analyzed the effects of supplemented diets on renal function (BUN and SCR) and lipid levels (TC and TG). The SCR levels in the C2‐10, GER, and PGER groups were significantly lower than those in the control group Table . The BUN3.4To determine the effects of supplemented diets on plasma and kidney antioxidant levels, we measured the levels of plasma and kidney antioxidant parameters  in the present experiment. The detected plasma CAT levels in SHR in the control, C2‐10, GER, and PGER groups were similar Table . However4γ‐Aminobutyric acid is a nonprotein amino acid that acts as a major inhibitory neurotransmitter in the central nervous system. Based on the fact that GABA accumulates in “Shangshida NO.5” giant embryo brown rice (GER) and germinated “Shangshida NO.5” giant embryo brown rice ,” a giant embryo rice developed in Korea (Ping et al., To test this hypothesis, in this study, the antihypertensive effects of diets supplemented with different brown rice derivatives were investigated, and the chronic administration of experimental diets containing C2‐10, GER, and PGER significantly decreased SBP in SHR Figure . The antThe antihypertensive mechanism of GABA in SHR has not been fully explained, but some possible mechanisms have been postulated. In the peripheral vasculature, possible mechanisms include ganglionic blockade (Vemulapalli & Barletta, In addition to GABA, giant embryo brown rice also contains more vitamin E, amino acids, and other nutrients (Wang et al., The kidney is the main target organ for hypertensive damage Raij, . Therefo. SOD plays a key role in scavenging free radicals in vivo, and CAT works closely with SOD to prevent free radical damage to the body (Kumar & Das, Oxidative stress plays an important role in the initiation and progression of cardiovascular diseases, including hypertension, type II diabetes, hypercholesterolemia, atherosclerosis, and heart failure (Hamilton et al., Altogether, our results showed that the administration of C2‐10, GER, and PGER significantly reduced SBP and DBP levels and ameliorated kidney function and antioxidant capacity. Given that brown rice and germinated brown rice can be eaten as part of a natural diet, GABA‐enriched “Shangshida NO.5” rice could be a good candidate for the prevention of hypertension.The authors declare that they do not have any conflict of interest.“This study was approved by the Institutional Review Board of Shanghai Jiaotong University.”Written informed consent was obtained from all study participants. Click here for additional data file.


The Marijuana Problems Scale (MPS) is a widely-used self-report measure of cannabis-related negative consequences that has a past three-month reporting window. This report describes the psychometric characteristics of a lifetime version (MPS-L).As part of a larger study, 119 individuals who had recovered from cannabis use disorder completed the MPS-L on two occasions 2 weeks apart and 91 participant-nominated family and friends also completed a collateral version of the scale.r = 0.81 and 0.73). As expected, correlations with collateral reports were moderate (r = 0.33 and 0.29), and collaterals reported significantly fewer negative consequences than participants. MPS total scores also correlated as expected with external validity measures . PCA supported the use of a total score summed score, but also revealed two secondary factors, measuring internal consequences  and external consequences .Item analyses and principal component analysis (PCA) revealed that three of the 19 items were relatively weaker. Omitting these items, the MPS-L showed good internal reliability  and test-retest reliability  were assessed.•Two scoring methods for the MPS-L total score showed good internal and two-week test-retest reliability.•The summed severity total score performing slightly better than the total number of consequences endorsed.•Collateral reports from family and friends and responses to a variety of related measures supported the validity of the MPS-L. The MarThe MPS was developed by Stephens and colleagues for their research program on cannabis treatment by adapting items from other drug use severity instruments . The 19 r = 0.70 or greater), and a lower but significant relationship with the collateral report on the same items (r = 0.30–0.40). Given the comorbidity between depression and cannabis use disorders  and interviews were conducted a mean of 10.3 days after the participant interview (SD = 7.7). The collaterals included 21 partners, 17 parents, 17 friends, 3 children, and 6 other types of family members. For the remaining 28 participants, 7 did not provide a collateral, 14 provided names but the collateral was unable to be contacted, and 7 provided names that were contacted but were unwilling to participate. Collaterals provided responses to the MPS-L items and were also asked to rate their confidence in responding to the MPS-L items overall . The mean confidence score was 3.2 (SD = 0.9), with a mode of 4 and a range of 1 to 4.Participants were re-contacted within two weeks after their initial interview to assess test-retest reliability of their self-reported cannabis use as well as responses to a variety of the assessment instruments . TelephoEthical approval was provided by the Conjoint Faculties Ethics Review Board at the University of Calgary.2.2The MPS was modified to inquire whether each item had ever been experienced as a problem, using the same response options as the three-month version . Two summary scores were calculated, a total summed score of the severity ratings  and a total problem score .Lifetime cannabis use disorder was assessed using the Composite International Diagnostic Interview (CIDI) , which wThere were three additional external validity measures used in this report. The Marijuana Motives Measure (MMM)  providesLifetime depressive symptoms were measured with the lifetime version of the 19-item Inventory to Diagnose Depression (IDD) . The parTreatment involvement was assessed by asking whether the participant had ever received at least one session of formal or professional treatment for a cannabis use problem . The interviewer probed and clarified responses. Involvement in self-help groups was excluded.2.3T-tests were used to compare the MPS-L total scores for participants who had or had not attended cannabis treatment. Pearson correlations were conducted between participants and collateral reports for each MPS-L item and total scores.As a preliminary step, corrected item-severity total summed scores correlations and principal component analysis of the item pool were computed to identify any weak items. Next, descriptive analyses of each of the MPS-L items and total scores were conducted. To assess internal reliability, coefficient alpha was conducted for both the summed severity total and the number of symptoms total. Internal reliability scores of 0.80 and greater are considered good. For test-retest reliability, Pearson correlations were computed for each MPS-L item and the total scores. To assess the validity of the total scores, Pearson correlations were computed with the number of lifetime DSM-5 symptoms (CIDI), the five MMM scales, and the lifetime severity of depression score (IDD). Finally, a principal component analysis was conducted to explore the factor structure of the scale. The ordinal responses to the items were used in the polychoric correlation matrix. Two methods were used to determine the number of components to rotate: Cattell's scree test, and Horn's parallel analysis . Varimax3Initial examination of corrected item-summed severity total score correlations ) revealer = 0.94. r = 0.81 vs. 0.73). The total scores did not differ significantly from the initial to retest administration  and 15.0 (8.6), t(104) = 1.96, p < .06; MPS-number M = 10.4 (4.0) and 9.8 (4.4), t(106) = 1.89, p < .07).The internal reliability for the remaining 16 items, assessed with Coefficient alpha, for both total scores was good for both total scores . The total scores correlated highly, t(117) = 4.07, p < .0001)) and the MPS- number (M = 11.6 (3.9) vs. 9.1 (3.9); t(117) = 3.53, p < .001)).t(90) = 3.85, p < .001 and t(90) = 3.3, p < .001, showing that collaterals were aware of fewer difficulties than participants. The Pearson correlations between collaterals and participants was r = 0.33, p < .001, for MPS-L-severity and r = 0.29, p < .007 for MPS-L-number.r = 0.59). Mean scores on factor one  were significantly higher than scores on factor two , which is consistent with the interpretation that these effects are more common, t(118) = 7.59, p < .0001).The principal components analyses showed that the Kaiser-Meyer-Olkin Measure of Sampling Adequacy was good (0.83) and all items loaded on the first unrotated component , which suggests that all items are measuring a similar construct. Both the Scree test and the Parallel test indicated rotation of two factors, which together accounted for 46% of the variance. The Varimax rotated loadings are displayed in 4The lifetime version of the MPS shows acceptable psychometric qualities in this community sample of individuals with a past CUD. The scale items measure common and less common negative consequences of cannabis use, but the total score is a reliable indicator of an overall level of problems. Although the scores for both the summed severity total and the total number of problems endorsed performed reasonably well and are highly correlated, the severity score generally was slightly stronger. This finding makes sense as the severity total captures the level of impact whereas the number of problems total score equates items having minor and major effects. Unless there is particular interest in the number of problems endorsed, it is advisable for researchers to use the MPS-L severity total score. Clarity in published reports about which scores are used in important. In previous research, the method of computing a total score for the three-month version of the MPS is sometimes not readily apparent.Participants showed good test-retest reliability at the individual item level and, in particular, for the total scores. Collaterals tended to report fewer negative consequences than participants  and the total scores were only moderately correlated. This finding is not unexpected as collaterals tend to be less aware of some negative effects, and most of the negative consequences would have occurred a number of years prior given that all participants were in recovery from CUD.Preliminary analyses revealed that three of the 19 original items seemed relatively weak, and were therefore excluded in the MPS-L. One of these items concerns blackouts, which is not a typical effect of heavy cannabis use. The MPS items have also been used to measure negatives effects of alcohol, so it is likely that this item was useful in that context. The other weak items were medical and legal problems, which both have some face validity for cannabis. The term “medical problems” is vague and may also be more associated with alcohol use . Legal problems are culturally influenced and vary from jurisdiction to jurisdiction, and over time. Because of this, experiencing legal problems related to substance use was dropped as diagnostic criteria in the DSM-5 for all substance use disorders and gambling disorder.Unfortunately, this investigation only included individuals who were no longer experiencing CUD, however, it is likely that the scale would perform as well, or even better with people reporting on more recent effects. Nonetheless, this should be investigated in future studies. It is also important to note that sample was comprised largely of middle-class Caucasian Canadians. Psychometric analyses of the scale in other populations is important. As well, this study did not examine content validity. Whether additional items should be included in a scale comprehensively measuring negative consequences could also be further investigated. Despite these limitations, these analyses provide preliminary support for a lifetime version of the MPS-L. An index of negative consequences of cannabis use with a lifetime reporting frame has not previously been available.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors, although JS received scholarship support from the Canadian Institutes of Health Research, Alberta Innovates Health Solutions, and the Killam Trusts.


Although alopecia affects the quality of life, its pathogenesis is unknown, because cellular interactions in the hair follicle are complex. Several authors have suggested using herbal medicine to treat alopecia, and bioinformatics and network pharmacology may constitute a new research strategy in this regard because herbal medicines contain various chemical components. This study used association rule mining (ARM) and network analysis to analyze the combinations of medicinal herbs used to treat alopecia.We searched Chinese, Korean, and English databases for literature about alopecia treatment, extracting the names of each herbal prescription and herb. The meridian tropism and classification category of each herb were also investigated. Using ARM, we identified frequently combined two-herb and three-herb sets. Using network analysis, we divided the herbs into several modules according to prescription pattern.Polygonum multiflorum Thunb. (何首烏) and Angelica sinensis (Oliv.) Dlels (當歸). The most frequently used three-herb combination was Polygonum multiflorum Thunb., Angelica sinensis (Oliv.) Dlels, and Ligusticum chuanxiong Hort. (川芎). In network analysis, three modules were identified. The herbs of Module 1 were related to the liver and kidney meridians, and those of Module 3 were related to the Stomach meridian.Fifty-six articles and 489 herbal medicines were included—312 internal and 177 external medicines. Among the 312 medicinal herbs used in internal medicine group, the most frequently combined two-herb set was We identified the frequency, characteristics, and functional modules of herb combinations frequently used in alopecia treatment. We confirmed the value of classical medicinal herb theory. This finding will prompt further bioinformatics and network pharmacology research on alopecia.The online version of this article (10.1186/s12906-018-2269-7) contains supplementary material, which is available to authorized users. Hair loss affects up to 50% of both men and women throughout their lives, causing anxiety and disability that can have a significant effect on the patient’s quality of life. , 2 The cFinasteride and minoxidil have been approved by the Food and Drug Administration of the United States  to promote hair growth. However, the effectiveness of these drugs varies greatly among individuals, and they have unwanted side effects. Relatedly, many alopecia patients are concerned about the side effects associated with conventional therapies, and complementary and alternative medicine (CAM) has thus been suggested as a new treatment for alopecia.  In partiHerbal medicine prescriptions consist of various herbal preparations. Thus, using the scientific method, researchers must investigate frequently used herbal combinations and categorize them. However, in the TCM literature, few narrative reviews have focused on herbs for alopecia treatment, , 7 and tqi and blood (氣血兩虛), qi stagnation and blood stasis (氣滯血瘀), and blood-heat (血熱) are the main patterns linked to alopecia. [Previous studies based on TCM pattern identification have shown that deficiency of liver and kidney (肝腎不足), deficiency of lopecia. , 7 Howevlopecia.  RecentlyTherefore, this study aimed to identify—using association rule mining (ARM)—which herbal combinations are used frequently in hair loss treatment and to analyze the modular characteristics of these treatments using network analysis.We included all kinds of studies regardless of the study design, and we did not restrict the type of alopecia or herbal medicine used. Thus, all kinds of herbal medicines were considered—extracts, decoctions, pills, and even external application. There were no restrictions on sex, age, disease duration, or disease severity. The outcome of clinical studies was not considered.We conducted an electronic search of the Chinese, English, and Korean databases from their inception to March 2017. We searched one Chinese database: the China National Knowledge Infrastructure (CNKI) database, three English databases: Embase, Medline (via PubMed), and the Central Register of Controlled Trials (CENTRAL), and one Korean database: the Oriental Medicine Advanced Searching Integrated System (OASIS), which specializes in traditional Korean Medicine research articles.  The follChinese Pharmacopoeia 2015 edition, [http://boncho.kiom.re.kr/herbarium/codex.php). [Phytology [Chinese Pharmacy. [Qi-regulating medicinal (理氣藥), (9) Digestant medicinal (消食藥), (10) worm-expelling medicinal (驅蟲藥), (11) hemostatic  (止血藥), (12) Blood-activating and stasis-dispelling medicinal (活血祛瘀藥), (13) Cough-suppressing and panting-calming medicinal (止咳平喘藥), (14) Tranquillizing medicinal (安神藥), (15) Liver-pacifying medicinal (平肝藥), (16) Orifice-opening medicinal (開竅藥), (17) Tonifying and replenishing medicinal (補益藥), (18) Astringent medicinal (收澁藥), (19) Emetic medicinal (湧吐藥), and (20) External application medicinal (外用藥).We extracted the name of each herbal formula, the medicinal herbs that comprised it, its origin (name of article or ancient literature), author, publication year, and internal/external application. The names of the herbs followed the edition, , 10 whicex.php).  The catehytology  and Chinharmacy.  The namePhytology [Chinese Pharmacy. [First, we compared the meridian tropism and classification category of each medicinal herb between the internal and external applications. The criteria for meridian tropism followed the classification of the hytology  and Chinharmacy.  Next, weUsing the list of prescriptions used to treat hair loss, we searched for combinations of herbs repeatedly used over several prescriptions. For this purpose, we applied ARM, which uncovers interesting relationships in large datasets, to our data.  Because https://networkx.github.io/). [ARM cannot inspect the overall pattern of how herbs are used together, because it assesses the association between limited numbers of itemsets. Therefore, we constructed a network that connected the herbs used together in alopecia prescriptions. We also examined the modularity analysis to identify patterns and group herbs into specific modules. The network between the herbs was configured using Python’s networkx® package (ub.io/).  The nodeub.io/).  Modulariub.io/). . Visualip-value was then calculated based on the location of the observations within the simulated null distribution. We tested 12 meridian preferences separately for each module, with a correction for multiple testing using the false discovery rate.To observe differences among the modules identified modularity analysis, the meridian tropism of the herbs composing each module was examined. Meridian tropism is the notion that a herb predominantly exerts a therapeutic effect on a specific organ or meridian in the human body . The merA total of 585 articles were screened: 286 in the English databases, 73 in CNKI, and 226 in OASIS. Ultimately, 56 articles were included after screening of the full text: 12 from the English databases, –30, 13 fFrom the 56 articles, 489 herbal medicines  and 374 medicinal herbs were identified. Among the 312 internal medicines, 258 medicinal herbs were identified. Among the 177 external medicines, 257 medicinal herbs were identified. Many medicinal herbs were used in both internal medicine and external applications. Table Polygonum multiflorum Thunb. (何首烏) and Angelica sinensis (Oliv.) Dlels (當歸) had the highest support, with 38.5%. The six possible pairs from a group of 4 herbs—Polygonum multiflorum Thunb. (何首烏), Angelica sinensis (Oliv.) Dlels (當歸), Ligusticum chuanxiong Hort. (川芎), and Rehmannia glutinosa Libosch. (Prepared) (熟地黃)—were listed as the top 6 association rules, indicating that these four herbs are the most commonly prescribed herbs, and that they are frequently used together. Other rules in the top 10 list contained Ligustrum lucidum Ait. (女貞子), Lycium barbarum L. (枸杞子), and Eclipta prostrata L. (旱蓮草) as additional combination herbs.The frequency trend of the 258 herbs in the 312 internal alopecia prescriptions were analyzed using the a priori ARM method to elucidate whether certain herbs are used more frequently in combinations of two or three. The top 10 association rules between two herbs are described in Table Polygonum multiflorum Thunb. (何首烏), Angelica sinensis (Oliv.) Dlels (當歸), Ligusticum chuanxiong Hort. (川芎), and Rehmannia glutinosa Libosch. (Prepared) (熟地黃)—three combinations were listed in the top 4 association rules, with support of 23.4, 21.5, and 21.2%, respectively. One other three-herb combination of the four main herbs, excluding Angelica sinensis (Oliv.) Dlels (當歸), was listed as the No. 8 association rule.The top 10 association rules for three-herb combinations are described in Table Paeonia lactiflora Pall. (白芍藥) did not appear in the top 10 association rules of two-herb combinations, but it was listed as a member of three-herb combinations in association rule Nos. 5 and 9. Cuscuta chinensis Lam. (菟絲子) was also not shown in the top 10 association rules of two-herb combinations, but it did appear among the top 10 association rules of three-herbs combinations.Based on the frequency of co-occurrences of herb pairs, we constructed a weighted unidirectional network, assigning “frequency of co-occurrence” as a weight value of the connection. We then performed a modularity analysis on the weighted graph using the Louvain method. The results showed that the network could be divided into three modules, with a modularity value of 0.141. The number of herbs comprising each module were 58, 86, and 111, respectively Fig. . UnconneThe frequency trend for meridian tropism in each module is described in Fig. Polygonum multiflorum Thunb., Angelica sinensis (Oliv.) Dlels, Rehmannia glutinosa Libosch. (Prepared), and Ligusticum chuanxiong Hort. Conversely, Platycladus orientalis (L.) Franco, Angelica dahurica (Fisch. ex Hoffm.) Benth. et Hook.f., Vitex trifolia L. var. simplicifolia Cham., and Ligusticum chuanxiong Hort. were frequently used in external applications. Internal medicine and external application differed in terms of pharmacological efficacy and meridian tropism. Using the ARM method, the most frequently used two-herb combinations were (1) Polygonum multiflorum Thunb. and Angelica sinensis (Oliv.) Dlels, and (2) Ligusticum chuanxiong Hort. and Rehmannia glutinosa Libosch. (Prepared). Ligusticum chuanxiong Hort., Polygonum multiflorum Thunb., and Angelica sinensis (Oliv.) Dlels was the most frequently used three-herb combination. Using the network analysis method, we classified the herbs into three modules. The meridian entry (歸經) of many herbs in module 1 was “Liver,” whereas that in module 3 was “Stomach”.We systematically searched literature for alopecia treatment formulas. The following herbs were frequently used in internal medicine: qi and flavor (氣味), and they exhibit curative effects on selected meridians. Therefore, depending on whether it belongs to the viscera or bowel group (臟腑), each medicinal herb is mainly used in a specific region. In other words, meridian tropism is a theory of the orientation of drug action. [The meridian tropism theory is important in traditional East Asian medicine—both pharmacologically and in clinical practice.  Accordin action.  Several  action. –76Polygonum multiflorum Thunb., Angelica sinensis (Oliv.) Dlels, Rehmannia glutinosa Libosch. (Prepared), Ligusticum chuanxiong Hort., and Poria cocos (Schw.) Wolf—appeared in order. When we analyzed the top 10 medicinal herbs in the internal medicine group, every herb except for Ligusticum chuanxiong Hort. belonged to the viscera meridian (臟), not the bowel meridian (腑). [Platycladus orientalis (L.) Franco, Angelica dahurica (Fisch. ex Hoffm.) Benth. et Hook.f., Vitex trifolia L. var. simplicifolia Cham., Ligusticum chuanxiong Hort., and Aconitum carmichaelii Debx.—appeared in order. Six herbs in external application group belong to the bowel meridian. [In the present study, the internal medicine group—ian (腑).  In the eeridian.  These dieridian.  The catePolygonum multiflorum Thunb., Angelica sinensis (Oliv.) Dlels, Ligusticum chuanxiong Hort. and Rehmannia glutinosa Libosch. (Prepared) are the main herbs used in alopecia treatment. The six two-herb combinations of the four main herbs were the top six combinations of two-herb sets. These four main herbs were also important in the three-herb sets. However, the three-herb combination of Polygonum multiflorum Thunb., Ligusticum chuanxiong Hort., and Rehmannia glutinosa Libosch. (Prepared) occupied the relatively low 8th place. Paeonia lactiflora Pall. did not appear in the two-herb sets, but it was frequently observed in the three-herbs sets, indicating that this herb is used as an adjunct in alopecia treatment.We identified frequently used two-herb and three-herb set combinations Tables  & 3. PolLigustrum lucidum Ait. and Eclipta prostrata L. combination was higher than the frequency and support values, and these herbs often appeared together with Polygonum multiflorum Thunb. or Angelica sinensis (Oliv.) Dlels. That said, all the medicinal herbs appeared frequently. In contrast, in the case of Ligustrum lucidum Ait. and Eclipta prostrata L., the lift value was higher than the frequency of each medicinal herb, indicating that Ligustrum lucidum Ait. and Eclipta prostrata L. are usually prescribed together. The herbal formula name of the Ligustrum lucidum Ait. and Eclipta prostrata L. combination is Yijihwan (二至丸). It has antioxidant activity and has been prescribed for hair loss in clinical practice. [Ligustrum lucidum Ait., Eclipta prostrata L., and Polygonum multiflorum Thunb. combination was also relatively high.Interestingly, the lift value of the ractice.  Among thqi stagnation (氣滯血瘀), dual deficiency of qi and blood (氣血兩虛), liver-kidney depletion (肝腎不足), and spleen-stomach dampness-heat (脾胃濕熱) were the major pattern identifications in alopecia. Pathology was classified in terms of the viscera and bowels (臟腑) theory or the qi and blood (氣血) theory.When we use the ARM method, the number of herbs that comprise each herb set should be determined in advance. For this reason we only identified frequently used two-herb and three-herb sets Tables  & 3, andqi and blood. [According to our network analysis, Module 1 herbs affect the “Liver” meridian more and seem to tonify d blood.  Module 3d blood. , 79–81 IPoria cocos (Schw.) Wolf and Glycyrrhiza uralensis Fisch. belonged to Module 1 and the “Liver” meridian (Table Ligusticum chuanxiong Hort. belonged to the viscera (臟) group and not the bowel (腑) group. In contrast, of the top 10 herbs in the external application group, five belonged to module 2. They also affected bowel meridians such as the “Stomach,” “Large intestine,” and “Urinary bladder.” Thus, it may be that Module 2 is associated with external application, but further study will be needed, as we only conducted network analysis on the internal medicine group. Many of herbs in Module 3 belong more to the “Stomach” meridian. However, there were not module 3 medicinal herb in the internal and external groups top 10 herbs, with the exception of Poria cocos (Schw.) Wolf and Glycyrrhiza uralensis Fisch., indicating that treatment of digestion and absorption, which are related to Module 3, may be an adjunctive strategy in traditional Asian medicine. However, further research is needed in this regard.Among the top 10 herbs in the internal medication group, none belonged to Module 2. All herbs except for Qi-regulating medicinals (理氣藥) occupy half of Module 3. Most of these were oriented towards the “Spleen” and “Stomach” meridians. Therefore, Module 3 herbs are related to digestive function.Additional analysis was conducted on the top 20 medicinal herbs of each module Table . In ModuModule 2 comprised five exterior-releasing medicinals (解表藥), three interior-warming medicinals (溫裏藥), and three blood-activating and stasis-dispelling medicinals (活血祛瘀藥). , 13 ThusExisting studies on pattern identification have taken a top-down theoretical approach. In contrast, the present research adopted a practical, bottom-up approach based on formulas that are prescribed in clinical practice. We conducted this novel approach to pattern identification by carrying out a network analysis of medicinal herbs used in alopecia treatment. We rediscovered the classical pattern identification of alopecia treatment, and we suggest that clinicians adopt a “Liver” or “Stomach”-oriented approach to alopecia treatment.The current research had several strengths. To our knowledge, this was the first study that used bioinformatics methods and searched Chinese, English, and Korean databases to assess which medicinal herbs have been used to treat alopecia. We adopted a practical network analysis approach based on formulas that are frequently used in clinical practice, rather than a theoretical/literature approach. Using this method, we explored the frequency, combination patterns, and meridian tropism of medicinal herbs used in alopecia treatment. We also classified herbs into three modules, confirming the value of classical pattern identification and the meridian tropism theory. Moreover, we explored the pathology of alopecia from the perspective of traditional east Asian medicine.Our data mining methodology, which employed ARM and network analysis, also had several strengths. Firstly, in the ARM method, the number of herbs comprising the combination must be determined in advance. To overcome such shortcomings, we used network analysis to look at the overall combination pattern of medicinal herbs without limiting the number of herbs in the combination. Secondly, previous top-down research based on ancient literature has offered hypotheses about the pattern identification category of alopecia. In contrast, our bottom-up study categorized herbs into three modules based on the combination patterns of the formula. Lastly, previous research was limited in that it could only “qualitatively” interpret the characteristics of medicinal herbs or formulas used in alopecia treatment. We overcame this limitation by extracting significant “quantitative” characteristics using the permutation test.Our research also had several limitations. The present study was based on the frequency of formulas used in clinical practice and literature. For this reason, we could not evaluate new candidate medicinal herbs emerging from recent clinical/experimental studies, neither could we reflect the importance of medicinal herb dose in each formula. Relatedly, we did not evaluate the clinical effectiveness of each formula in our study. Further clinical/experimental studies are needed to assess whether the classifications derived from our research have real meaning. Meridian tropism theory is controversial and may not accurately reflect the characteristics of each medicinal herb. Finally, we did not analyze external medicine, and the heterogeneity within Module 2 was not completely resolved.The present research raises several indications for future research. We should analyze externally applied alopecia treatments, and we need to conduct a proof-of-concept study to corroborate our research. Using network pharmacologic analysis of medicinal herbs in each module, a hair loss mechanism could be identified based on meridian tropism theory . Such studies may also indicate the pharmacological mechanism of hair loss treatment (western medicine theory). Multi-component, multi-target concepts are essential in herbal medicine pharmacology. Thus, we could propose new research methodology based on the techniques used in the present study. This methodology could be utilized to develop new hair loss drugs from natural products.Polygonum multiflorum Thunb. and Angelica sinensis (Oliv.) Dlels. The most frequently used three-herb combination was Polygonum multiflorum Thunb., Angelica sinensis (Oliv.) Dlels, and Ligusticum chuanxiong Hort. Based on the meridian tropism theory, we used network analysis to identify three modules of herbs that can treat alopecia. We found a “Liver”-oriented module and a “Stomach”-oriented module, and confirmed the value of classical meridian tropism theory and pattern identification. However, further clinical/experimental study is needed to prove the significance of this concept and methodology.We identified the frequency and characteristics of medicinal herbs used in alopecia treatment. The most frequently used two-herb combination in alopecia treatment consisted of Additional file 1:Search strategy according to database. Individual search strategies for each database (DOCX 15 kb)


Fusarium fujikuroi, has become a serious threat in rice-cultivating regions worldwide. In the present study, quantitative trait locus (QTL) mapping was performed using F2 and F3 plants derived after crossing a BD-resistant and a BD-susceptible Korean japonica rice variety, ‘Samgwang’ and ‘Junam’, respectively. Resequencing of ‘Junam’ and ‘Samgwang’ genomes revealed 151,916 DNA polymorphisms between the two varieties. After genotyping 188 F2 plants, we constructed a genetic map comprising 184 markers, including 175 kompetitive allele-specific PCR markers, eight cleaved amplified polymorphic sequence (CAPS) markers, and a derived CAPS (dCAPS) marker. The degree of BD susceptibility of each F2 plant was evaluated on the basis of the mortality rate measured with corresponding F3 progeny seedlings by in vitro screening. Consequently, qFfR9, a major QTL, was discovered at 30.1 centimorgan (cM) on chromosome 9 with a logarithm of the odds score of 60.3. For the QTL interval, 95% probability lay within a 7.24–7.56 Mbp interval. In this interval, we found that eight genes exhibited non-synonymous single nucleotide polymorphisms (SNPs) by comparing the ‘Junam’ and ‘Samgwang’ genome sequence data, and are possibly candidate genes for qFfR9; therefore, qFfR9 could be utilized as a valuable resource for breeding BD-resistant rice varieties.Bakanae disease (BD), caused by the fungal pathogen  Fusarium fujikuroi, has become a serious global threat in the majority of the rice-cultivating regions, leading to high (3.0–95.4%) losses in yield [Fusarium fujikuroi also produces fusaric acid, a phytotoxin that causes stunted growth [Bakanae disease (BD), caused by the fungal pathogen in yield ,2,3,4,5.in yield . Fusariud growth . BD exhid growth . The optFusarium fujikuroi is a seed-borne pathogen. The ascospores and conidia adhering to the seed act as the primary source of inoculum, whereas the hyphae infect seedlings through the roots and crown [nd crown . The trend crown . Howevernd crown ,8,9. TheSeveral methods have been developed to screen for BD-resistant germplasms. According to Fiyaz et al. , a high-qBK1.1, qBK1.2, and qBK1.3) on chromosome 1 were detected using recombinant inbred lines derived from two indica rice parental varieties; namely ‘Pusa 1342’ and ‘Pusa Basmati 1121’, the former being a highly resistant variety and the latter a highly susceptible variety [qBK1) in a 520 kb region between RM8144 and RM 11295 on chromosome 1 using 168 near-isogenic rice lines (BC6F4) derived from a cross between ‘Shingwang’ and ‘Ilpum’, a highly resistant (indica) and a highly susceptible variety (japonica), respectively. Ji et al. [qFfR1) in a 22.56–24.10 Mbp region on chromosome 1 using 180 F2:F3 lines derived from a cross between a resistant Korean japonica variety, ‘Nampyeong’, and a susceptible Korean japonica line, ‘DongjinAD’. A QTL analysis using recombinant inbred lines derived from a cross between the resistant ‘Wonseadaesoo’ variety and the susceptible ‘Junam’ variety revealed a major QTL (WDqBK1) located at a 1.59 Mbp interval, delimited between chr01_13542347 (13.54 Mbp) and chr01_15132528 (15.13 Mbp), and the pyramiding of WDqBK1 and qBK1 was performed [qBK1_628091 and qBK4_31750955, on chromosomes 1 and 4 [Several quantitative trait locus (QTL) mapping studies have been conducted to better understand BD resistance. Yang et al.  reported variety . Hur et  variety  mapped aerformed . In addiF. fujikuroi in the resistant variety Selenio as compared with the susceptible variety ‘Dorella’ [F. fujikuroi induced an increase in the production of phytoalexins, particularly sakuranetin, in the resistant cultivar ‘Selenio’, while it induced the production of gibberellin and abscisic acid and inhibited the production of jasmonic acid, leading to very low levels of phytoalexins in the susceptible variety ‘Dorella’. A high-quality genome sequence of F. fujikuroi revealed gene clusters for the biosynthesis of secondary metabolites such as gibberellin and fumonisin [F. fujikuroi [Using RNA-seq, it was demonstrated that PR1, germin-like proteins, glycoside hydrolases, mitogen-activated protein kinases, and WRKY transcription factors are upregulated in response to Dorella’ . SiciliaDorella’  reportedumonisin . It has ujikuroi ,23.qFfR9, was discovered on rice chromosome 9, and it may prove useful for breeding BD-resistant rice varieties.In this study, we aimed to find novel QTLs for resistance to BD which will be used for breeding resistant rice varieties. We performed QTL mapping using F2 and F3 plants derived from crossing ‘Samgwang’ and ‘Junam’, BD-resistant and BD-susceptible Korean japonica rice varieties, respectively. The genotyping of F2 plants was performed using primarily kompetitive allele-specific PCR (KASP) markers developed from single nucleotide polymorphisms (SNPs) detected among Korean japonica rice varieties . A majorIn vitro seedling screening was used for investigating the response of ‘Samgwang’ and ‘Junam’ rice varieties to BD. In the case of ‘Junam’, the heights of the treated plants were greater than the control plants until 12 days after inoculation (DAI); subsequently, the heights of plants in both groups were observed to be similar a. In theThe degree of BD susceptibility of each F2 plant was evaluated on the basis of the mortality rate measured with corresponding F3 progeny seedlings by an in vitro seedling screening method at 4 weeks following inoculation. Analysis of variance was performed for testing the significance of differences between lines and replications . The dif6 reads containing 41.7 Gbp, with an average mapping depth of 111.83×, were mapped in case of the ‘Junam’ variety, whereas 200.0 × 106 reads containing 19.4 Gbp, with a mapping depth of 51.94×, were mapped in case of the ‘Samgwang’ variety. Between ‘Junam’ and ‘Samgwang’, 151,916 DNA polymorphisms including 140,318 SNPs and 11,598 InDels were detected. The number and distribution of DNA polymorphisms were highly varied and uneven among the chromosomes , while chromosome 8 harbored the lowest number (n = 2024). All chromosomes were composed of a mixture of dense and sparse SNP regions  markers and one derived CAPS (dCAPS) marker on chromosome 9 , and genqFfR9 was located at 30.1 cM, with an logarithm of the odds (LOD) score of 60.3  (http://rapdb.dna.affrc.go.jp/) database annotation, 15 genes were located in this interval  or intron or synonymous SNPs in protein-coding sequences. It can be expected that the functions of these genes may not be significantly different between the ‘Junam’ and ‘Samgwang’ varieties. A further eight genes showed non-synonymous SNPs, whose positions in the genes are shown in qFfR9.The QTL analysis using the revised map indicated that  of 60.3 . The addinterval a. A compinterval . The Os0For mapping a QTL encoding for BD resistance, we used a F2:F3 population derived from crossing BD-resistant ‘Junam’ and BD-susceptible ‘Samgwang’ varieties of rice. These varieties are both Korean japonica rice varieties and share the ‘Hwayeong’ variety as their genealogical parent. ‘Junam’ and ‘Samgwang’ are closely related; ‘Junam’ was bred from a cross of ‘Hwayeong’/’Sangju’/’Ilpum’ and ‘Samgwang’ from a cross of ‘Suwon361’/’Hwayeong’. Previously, we developed 400 KASP makers on the basis of SNPs detected among closely related Korean japonica rice varieties through genome resequencing . These mqB1 and qB10, were found in RM7180-RM486 region on chromosome 1 and RM1108-RM304 on chromosome 10 with LOD scores of 2.32 and 2.50, respectively, using a japonica/indica double haploid population [qBK1.1, qBK1.2, qBK1.3, were found in RM9-RM11282, RM10153-RM5336, RM10271-RM35 regions on chromosome 1 with LOD scores of 3.86, 12.07, 2.73, respectively, using recombinant inbred lines derived from a cross between a resistant indica rice variety, ‘Pusa 1342’, and a susceptible variety, ‘Pusa Basmati 1121’ [qBK1, was found in a 520 kbp region between RM8144 and RM11295 on chromosome 1 with an LOD score of 33.21 with 168 near-isogenic rice lines derived from a cross between ‘Shingwang’, a highly resistant indica variety, and ‘Ilpum’, a highly susceptible japonica variety. Also, in a similar region as qBK1, a major QTL, qFfR1, was mapped in a 22.56–24.10 Mbp region on chromosome 1 with an LOD score of 22.7 using 180 F2:F3 lines derived from a cross between a resistant Korean japonica variety, ‘Nampyeong’, and a susceptible Korean japonica line, ‘DongjinAD’ [WDqBK1 was located in a 1.59 Mbp interval of chr01_13542347-chr01_15132528 with an LOD score of 8.29 using the recombinant inbred lines (RILs) derived from a cross between ‘Wonseadaesoo’, a resistant japonica variety, and ‘Junam’, a susceptible japonica variety [qFfR9, located in the 7.24–7.56 Mbp region on chromosome 9 with a very high LOD score of 60.3 and an R2 value of 0.59. This is a novel QTL because no QTLs have been found on chromosome 9 before. The qFfR9 was found from a high-quality Korean japonica BD resistant rice variety, ‘Samgwang’, and this study is the first one to reveal the BD resistance gene of ‘Samgwang’. It can be inferred that ‘Samgwang’ has a BD resistance gene different from those of other BD-resistant varieties analyzed so far. It can be expected that the marker closest to qFfR9, KJ_09024, may be used as a selection marker for qFfR9 in future BD-resistant rice variety breeding programs using ‘Samgwang’ as a resistance donor parent.The previously reported QTLs for BD resistance were located on chromosomes 1, 4, and 10 ,16,17,18pulation . Three QqFfR9 region contained 15 genes, and 208 DNA polymorphisms were present in the genic regions of 14 genes  domain. The domain structure of the deduced protein of the Os0298700 gene is shown in Arabidopsis RRM domain protein, ENHANCED DOWNY MILDEW 3 (EDM3), reportedly mediates resistance to the downy mildew disease pathogen, Hyaloperonospora arabidopsis [edm3-1 mutant which lost resistance to Hyaloperonospora arabidopsis, the level of RPP7 full-length coding transcripts was substantially lower and non-coding proximal-polyadenylated transcripts were increased as compared to the wild type Col-5. If the Os0298700 gene confers resistance to BD via a similar function to that of EDM3, it might control the polyadenylation of another BD-resistance gene at proximal sites of the gene, which would change the ratio of functional full-length coding transcripts to non-coding proximal-polyadenylated transcripts. Further fine-mapping of the qFfR9 locus and functional analysis of candidate genes using mutants or transgenic plants are required for the exact identification of genes within this locus.The 14 genes . Notablybidopsis . EDM3 coThe ‘Junam’ and ‘Samgwang’ rice varieties were crossed in summer 2016 in a greenhouse at the National Institute of Agricultural Sciences (NIAS). ‘Junam’ and ‘Samgwang’ are Korean japonica varieties that are susceptible and resistant to BD, respectively . F1 and F. fujikuroi strain CF283 at a concentration of 105 spores/mL. The spores were harvested from the fungus grown on potato dextrose agar media for 1 week in an incubator at 28 °C. The seeds were planted on solid Murashige and Skoog (MS) medium contained in Incu Tissue jars  1 day after inoculation. Next, the Incu Tissue jars were placed in a tissue culture room at 28 °C under a 16/8 h light/dark cycle. At approximately 4 weeks after inoculation, when the seedlings of susceptible varieties were mostly dead; the live and dead seedlings were counted and the mortality rates were calculated by dividing the number of dead seedlings by the total number of seedlings.A BD response bioassay was performed on the basis of a modified in vitro seedling screening method as described in . BrieflyF. fujikuroi strain CF283, similar to the abovementioned method, and planted in three Incu Tissue jars. At 4 weeks following inoculation, most ‘Junam’ seedlings were dead; live and dead seedlings were counted and the mortality rates were calculated.To determine the mortality rate of each F2 plant derived from the ‘Junam’/’Samgwang’ cross, 60 F3 seeds from each F2 plant were inoculated with the spore solution of To inspect changes in ‘Junam’ and ‘Samgwang’ plant heights, 16 Incu Tissue jars containing 160 inoculated seeds (10 inoculated seeds per jar) and another 16 Incu Tissue jars containing 160 control seeds (10 control seeds per jar) were prepared for each parental variety. From 4 DAI to 32 DAI, the seedlings were removed from two Incu Tissue jars at 4 day intervals and plant heights were measured. To calculate the change in mortality rates of ‘Junam’ and ‘Samgwang’ seeds according to BD, three Incu Tissue jars containing 30 inoculated seeds (10 inoculated seeds per jar) and another three Incu Tissue jars containing 30 control seeds (10 control seeds per jar) were prepared for each parental variety. Mortality rate was measured by counting live and dead plants simultaneously as plant heights were measured.Oryza sativa L. cv. Nipponbare sequence  was used as a reference sequence. The CLC Assembly Cell program  was primarily used for read mapping and SNP detection. The generated reads were mapped on to the Nipponbare reference sequence using the clc-mapper command with the following parameters: alignment mode, local; similarity, 95%; gap cost, 3; deletion cost, 3; mismatch cost, 2; length fraction, 1.0; repeat, ignore. DNA polymorphisms relative to Nipponbare were detected using clc_find_variation command. On the basis of the detected DNA polymorphisms between ‘Junam’ and Nipponbare and between ‘Samgwang’ and Nipponbare, DNA polymorphisms between ‘Junam’ and ‘Samgwang’ were analyzed using Python programs developed in-house. The detected DNA polymorphisms were annotated as genic and intergenic based on positional information from the Rice Annotation Project Database . DNA polymorphisms in genic regions were classified as coding sequences (CDSs), untranslated regions (UTRs), and introns. The SNPs in the coding region were divided into synonymous SNPs and non-synonymous SNPs by amino acid substitutions. The sequencing data of ‘Junam’ and ‘Samgwang’ varieties have been submitted to the Sequence Read Archive (SRA) database of NCBI (https://www.ncbi.nlm.nih.gov/sra) under the accession numbers SRX5560097 and SRX5560098.We extracted genomic DNA from seedlings of ‘Junam’ and ‘Samgwang’ using a DNeasy Plant Maxi kit . Using a TruSeq DNA PCR-free kit , sequencing libraries were created following the manufacturer’s protocols, and the fragments of the libraries were paired-end sequenced using the HiSeq 2000 Sequencing System . The raw readouts that were graded as high-quality using Phred quality values of >Q20 were used to analyze genetic variations between the ‘Junam’ and ‘Samgwang’ varieties. The “Q20”value indicates an accuracy of 99% for the base called. The A total of 188 F2 plants obtained from the cross between ‘Junam’ and ‘Samgwang’ varieties were genotyped using KASP markers developed from SNPs detected among Korean japonica rice varieties . Using thttp://probes.pw.usda.gov/batchprimer3/). The designed CAPS markers were used for testing parental polymorphisms. PCR products amplified using the primers and parental DNA were digested overnight with restriction enzymes at 37 °C, and separated by electrophoresis on 1.2% agarose gels. Polymorphic CAPS markers were used to genotype F2 plants. Using the SNPs not lying within the restriction enzyme sites, but needed to be converted to markers. dCAPS markers were developed using the dCAPS FINDER 2.0 program (http://helix.wustl.edu/dcaps/dcaps.html).After discovering that a major QTL was located on chromosome 9, CAPS and dCAPS markers were developed on chromosome 9 on the basis of SNPs detected by the resequencing of ‘Junam’ and ‘Samgwang’ varieties. Among the detected SNPs, those lying in restriction enzyme sites were extracted, and CAPS markers were designed as follows: 500 bp left flanking sequences and 500 bp right flanking sequences of SNPs lying in restriction enzyme sites were used to design PCR primers using the BatchPrimer3 1.0 primer design program . The locations of DNA polymorphisms between ‘Junam’ and ‘Samgwang’ in the candidate genes were calculated based on the positional information of DNA polymorphisms acquired by the annotation procedure described in 4.2 and candidate gene coordinate information in the RAP-DB.The physical interval of the identified major QTL was deduced from the positions of left and right flanking markers of the QTL interval at 95% probability. The physical map of genes located in this physical interval was drawn from the genome browser of the Rice Annotation Project Database, RAP-DB  has become a serious threat to almost all rice-cultivating regions worldwide, leading to high (3.0–95.4%) losses in yield. Due to the occurrence of fungicide-resistant strains of BD, the development of BD-resistant rice varieties has become critical for disease control. In this study, we discovered a novel major QTL for BD resistance,


A vehicle-bridge tuned mass damper (TMD) coupled dynamic analysis and vibration-control model was established to optimize TMD damping effects on a steel-box girder bridge bearing vehicle loads. It was also used to investigate optimization efficiency of different algorithms in TMD design parameters. This model simulated bridges and vehicles with the use of a 7 degrees of freedom curved-beam element model and a 7 degrees of freedom vehicle model, respectively. The TMD system was simulated with the use of multiple rigid-body systems linked with springs and dampers. Road surface condition, as a vibration source, was simulated with the use of a frequency equivalent method based on a power spectrum. A variably-accelerated pattern search algorithm was proposed in line with the initial TMD parameters calculated by Den Hartog formula. Visual software was compiled by Fortran and used for an optimization study of vibration reduction. A three-span, curved, continuous steel-box girder bridge was used as the numerical example. Optimized effects and computational efficiency of vibration reduction under different methods were compared. The comparison included a single variable optimization based on Den Hartog formula, an ergodic search method, an integer programming method, a traditional genetic algorithm, a traditional pattern search algorithm, and a variably-accelerated pattern search algorithm. The results indicate that variably-accelerated pattern search algorithm is more efficient at improving TMD optimal parameter design. Final TMD parameter optimization values obtained by different methods are quite close to each other and tends verify the reliability of the optimization results. Vehicles moving on irregular bridge road surfaces produce coupling vibrations in the vehicle-bridge system. Large amplitude causes noise and driving discomfort and generates fatigue damage to the bridge structure. Presently steel-box girder bridges are widely used as urban overpasses as they can be rapidly constructed and do not need full construction support. Vibration and noise remain as drawbacks. Vibration control research on steel-box girder bridge dynamic responses under vehicle loads is of great theoretical significance and practical engineering value. Prior studies tended to analyze the coupled dynamic response of vehicle-bridge system –5. RecenThe present state of bridge damping research is focused on vibration control in railway concrete girder bridges and footbridges and optimizing TMD parameters based on a single variable analysis. Research on the unconstrained optimized damping of the TMD system of steel-box girder bridges under the effects of automobiles remains scarce. Vigorous restrictions have often been imposed to simplify calculations such as equal quality and even frequency distributions. A relatively simple linear search technology to obtain optimal TMD parameters is an example , 19, 20.The 7-DOF, spatial, curved-beam element, which takes constrained torsion into account, was used for the bridge in Element displacement parameters are:x, y, z, and θ are linear and angular displacements in the X, Y, and Z directions. φ is the rate of change of X-axis direction torsional angle.Subscript "1" and "2" are the left and right nodes respectively. Rayleigh damping is adopted for the bridge model. The element characteristic matrix is formed according to the total potential energy invariance of the elastic system dynamics principle. The "check mark" rule is used to form the matrix . OverallMs,Cs,Ks are structure mass, damping, and stiffness matrix in the global coordinate system, respectively. Ps is the structure external load vectors.In this formula (2), zc,zwa,zwb,zwc,zwd), front and rear body nodding (θyc), and vehicle lateral rolling motion (θxc) for a total of 7 DOFs. This fully simulates vehicle movement characteristics. Assuming that the vehicle is traveling at a constant speed parallel to the lane centerline, small displacement vibrations in the direction of the respective DOFs are considered. A centrifugal force for each concentrated mass acts on the respective mass center T. Mt, Kt, and Ct are the same, it is the distributed TMD system.In Eq , the TMDμ, frequency ratio α, and damping ratio ζ) is to find a suitable combination of parameters {μopt,αopt,ζopt} and to minimize the bridge displacement response Dz under the vehicle load:Steel structure low-frequency vibration takes displacement-based fatigue strength failure into account . A TMD sPresently, numerical optimization methods are used because the parameter optimization effect of analytic formula method on TMD is always limited, such as DH formula . TMD numWarburton  introducμ0,α0,ζ0}, a new search limit was determined within a certain range in Eq  which uses improved initial values. A Den Hartog (DH) formula is used to determine better initial search values and accelerate the convergence speed of traditional pattern search algorithm (PS). A traditional PS algorithm step length, and acceleration and deceleration, principles have been modified to improve search efficiency. Overall optimization is strengthened by improving initial values and traditional pattern search algorithm search processes. Partial search capabilities are improved and realize an optimal parameter solution for a TMD system.The procedure is as follows:α and damping ratio ζ of the n-TMD system at different mass ratios μ, which was used as one of the initial values of the variably accelerated pattern search algorithm.A Den Hartog formula was preliminarily used to calculate the frequency ratio n-TMD system parameters are selected according to the optimal displacement damping ratio.Using these search initial values, a VAPS algorithm performs vibration damping optimization calculations. Optimal The specific implementation is as follows.The initial TMD parameters determinations can be performed using the DH formula with no main structure damping as the steel-box girder bridge actual damping ratio is very small. Guo and Lu proved that the DH formula was still applicable to TMD control of vehicle-bridge coupling vibration . TMD sysμ is Eq ; 2) initial step adjustment coefficient η; 3) search lower bound vector L; and, 4) search upper bound vector R. The initial step is α= η(L+R); let initial acceleration factor δ≥1, step increase coefficient λ>1, and step decrease coefficient β∈. Acceleration factor δ adjustment factor is ρ. ei is the orthogonal basis used of traditional pattern search method to specify the search direction [ε. Let t1 = x(1), ρ = 1, η = 1 and pattern move search loop step number k = 1.Set TMD parameter optimization initial values as follows: 1) algorithm initial point irection . The terStep 2:α= η(L+R).Calculate the search step δ = ρ·δ, for i = 1, 2, …, n, the following judgment is made:Acceleration factor f(ti+α(i)ei)<f(ti): if f(ti−α(i)ei)<f(ti+α(i)ei), then make ti+1 = ti−α(i)ei,α(i) = λ·α(i);If f(ti−α(i)ei)≥f(ti+α(i)ei), then make ti+1 = ti+α(i)ei,α(i) = λ·α(i);if f(ti−α(i)ei)<f(ti), then make ti+1 = ti−α(i)ei,α(i) = λ·α(i);or, if ti+1 = ti.or, make Step 3:f(tn+1)<f(xk), then make ρ = f(xk)/f(tn+1), xk+1)(+δ(xk+1)(−xk), η = λ·η; then make k = k+1, and go to Step 2.If Step 4:t1≠xk)/f(tn+1), t1 = xk)|<ε, then stop the calculation; or, make η = β·η, and go to Step 2.If |η is no longer a number, but is an n×1 dimensional vector. At the beginning of the algorithm, initial step adjustment coefficients for all directions are equal. However, as detection movement progresses, the step adjustment coefficients in each direction varies according to function values in each direction. The η value returned either increase or decrease with structural maximum dynamic response results. After a cycle ends, it is then synchronically increased, or decreased, according to the overall situation. Similarly, the acceleration factor δ will increase, or decrease, as function value change after each mode movement. Therefore, a step in each direction probed by the VAPS algorithm can increase, or decrease, according to the function variation in each direction. This results in an algorithm mode movement direction closer to the optimal descent direction than an traditional PS algorithm. As the search progresses, the acceleration factor can be dynamically adjusted according to the objective function value change in the optimal descent direction. An optimum point is approached more quickly. When the search point closes to an optimum point, the acceleration factors decrease. This narrowing makes the searches for the final value of the algorithm more precise and facilitates finding the optimal point.The step adjustment coefficient n-TMD system parameter combination to be calculated according to the optimal displacement damping rate.This VAPS algorithm allows an optimal Changsha's Hongqi viaduct bridge is used as an example. It is a continuous girder bridge with a uniform cross-section steel-box and a (42+64+42)m span. It has 12 lanes, 6 lanes in each direction. Its centerline curve radius is 600m. The main girder beam height is 2.5m. The top plate width is 25m. The cross-section is a 4-chamber box section of a whole single box .An et al.  chose baVBTS-1 self-programming software established a curved beam element model . LongituRdyn and Rsta = bridge maximum dynamic and static responses, respectively.The dynamic impact factor (IM), which is the measure of vehicle-bridge coupled vibration effect, is calculated as follows :IM=; B (good); C (acceptable); and D (poor) were analyzed. The static displacement and the dynamic IM of the bridge midspan displacement under the vehicle load were calculated assuming that the single motorcade drove along the outermost lane with equal spacing and constant speed Figs  and 11. Resonance speed is 50km/h under C-level road condition. Bridge midspan spectrum curve response is calculated . StructuThis section discusses different TMD parameter optimization methods, considering both displacement response damping effect and optimization calculations time costs. It compares and evaluates various methods to obtain the most suitable TMD damping optimization method for a three-span curve continuous steel-box girder bridge.μ range was 0.001 to 0.05. The optimum frequency ratio αopt and damping ratio ζopt were determined using DH optimization formula. The maximum displacement dynamic response of the bridge midspan under various mass ratios were calculated (m = 17950kg). The corresponding 1-TMD initial optimization parameter is: {μ = 0.03,α = 0.9709,ζ = 0.1015}.A single TMD system was placed at the bridge midspan cross-section for the resonant vehicle speeds and controlled mode. The mass ratio lculated . DisplacK = 5285kN/m), response maximum value across the middle node was minimized. The 1-TMD parameter value was {μ = 0.03,α = 1.0237,ζ = 0.1015}.The frequency ratio range was 0.2 to 2.2. Mass ratio and damping ratio were unchanged. Bridge midspan response values were calculated . When thC = 24.62kNs/m, when the damping effect was optimal. A 3-TMD system divided equally in weight was placed in the midspan cross-section and symmetrically arranged along the cross-bridge at equal intervals, in order to avoid any adverse effect of a single TMD mass which might be too much heavy for the structure. Each TMD value is: {μ = 0.0100, α = 1.0237, ζ = 0.0134}. The maximum displacement of the bridge midspan were calculated as 5.052 mm and 0.677 m·s-2 respectively, whose vibration damping rates were 28.5% and 32.6%, respectively.The damping ratio range was 0.0 to 0.8. Mass ratio and frequency ratio remained constant. Bridge midspan response values were calculated . The curμ values was extracted. Using MATLAB [μ value was unchanged during the optimization process.An ergodic search was performed within the range of Eq . The maxg MATLAB , the surμ value often appears near the 3D graph boundary. An integer programming method can be used to calculate the power response corresponding to the parameter combination located on the ergodic search space boundary and an acceptable combination of parameters can be obtained more quickly; and, 3) The traditional PS algorithm, under the initial value of DH results, is consistent with the ergodic search method, and quickly approached the "bottom" with short calculation times. The best vibration damping solution is better than the ergodic search. Specific optimum parameters and damping effects are in Section 6.6.The analysis shows that: 1) under different TMD parameters combinations, structural maximum displacement responses vary greatly. It has no consistent change trend and shows a strong irregularity. In μ, α, ζ} parameter combination corresponding to the points on the six boundary faces are selected to calculate the bridge dynamic response after installing a TMD. The specific optimum parameters and damping effects are presented in the following Section 6.4. The calculation number is selected as the abscissa. The ordinate of the corresponding dynamic response result, is plotted in Section 6.2 gave the results for an ergodic search solution space formed by Eq . The {μ,This section compares the GA algorithm and the PS algorithm to confirm the applicability to solve the TMD vibration optimization problem. A "roulette" selection operator in the GA algorithm results in differing optimization processes . The folμ, α, ζ} parameter of the traditional PS algorithm search range is smaller than the traditional GA algorithm. Its overall search ability is not as good as the latter but it quickly converges under superior initial optimization values. Optimization results quite close to the latter are obtained with relatively few calculations and reflect the superiority of the traditional PS algorithm in the TMD damping optimization analysis; 2) Under the two optimization algorithms, the final values of {μ, α, ζ} are quite similar, which tends to confirm the reliability of the optimization results.The analysis shows that: 1) the {μ values. Results are compared  With an initial DH value when μ = 0.02, a VAPS algorithm has a greater number of calculations compared to a traditional PS algorithm. But it achieves superior damping optimization results with higher optimization guarantees compared to a traditional PS algorithm, whose premature convergence causes a less effective optimization. 4) Final {μ, α, ζ} values, returned by the two optimization algorithms are quite close, the difference <5%, which tends to confirm optimization reliability.The results show that: 1) the two PS algorithm both converge quickly under different initial values and their convergent results are close. This indicates that the dependence of PS method on initial value has been improved under the DH formula; 2) The VAPS algorithm achieves superior optimization results with fewer calculations using β, is defined as:The displacement damping rate for the TMD system, Dz is the absolute value of the maximum displacement at the corresponding bridge node installed with the TMD system; D0 is the absolute value of the maximum static displacement without TMD system; Dmax is the absolute value of the maximum dynamic displacement without TMD system.The optimal parameter combination of 3-TMD obtained via different optimization methods and the corresponding optimization calculation times are extracted. The vibration-damping effect is calculated according to Eq  and summThe results show:The traditional GA algorithm, the traditional PS algorithm, and the VAPS algorithm have superior optimization results when measured by displacement damping rate. A Den Hartog formula-based, single-variable optimization method has the worst effect.The VAPS algorithm has the fewest calculations and the most efficient vibration damping optimization calculation rate. When compared to traditional PS algorithm, a VAPS algorithm can often reduce time by half. The other methods' optimization efficiency is deficient by comparison. Traditional GA algorithm and ergodic search methods could take 10 times as long.Results can be achieved through an integer programing method with fewer calculations and are close to ergodic search methods. The number of calculations can be reduced more when densely partitioning the ergodic search grid.μ, α, ζ} values obtained by the traditional GA algorithm, the traditional PS algorithm and the VAPS algorithm are quite close and tend to confirm optimization results reliability.The optimized final {μ, α, ζ} over a large range with certain overall search capabilities.The VAPS algorithm under an initial DH value requires relatively few calculations. It can accelerate TMD damping optimization calculation convergence rates in the premise of superior vibration damping effect. It can also search for parameter combinations of {Comparing the operating conditions before, and after installing, the TMD system, the optimal 3-TMD displacement damping effects are calculated and shown in f = 2.665Hz) is achieved, thereby effectively reducing the bridge dynamic responses.The frequency response result of the acceleration time-history response dispersed by Fourier transform is shown in For the optimization problem of vehicle-bridge coupling damping for steel box-girder bridges, a dynamic analysis model of vehicle-bridge-TMD coupled system was established. A variably accelerated pattern search algorithm based on a Den Hartog formula was proposed. The VBTS-1 software with a visual interface, programmed in Fortran language, was used for an optimization study of vibration damping. A three-span curved continuous steel box girder bridge situated on Hongqi Road, Changsha was taken the example. A discussion on the parameter optimization of TMD system was performed. Their optimized effects under different methods were compared. The comparison included a single variable optimization method based on a Den Hartog formula, an ergodic search method, an integer programming method, a traditional genetic algorithm, a traditional pattern search algorithm, and a variably accelerated pattern search algorithm. Finally, the vibration reduction effects before and after the optimized TMD system installation were compared. The main conclusions are as follows:Comprehensively considering displacement response damping effects and the optimization calculations time cost, a VAPS algorithm under Den Hartog initial values has relatively fewer calculation times and the optimization effect seem certain compared to various TMD parameter optimization methods. A single-variable optimization method based on a Den Hartog formula has the least calculation number but the least effective damping effect. A traditional GA algorithm has the best damping effect, but the longest calculation time.Final TMD parameter optimization values obtained by different methods are quite close to each other and tend to verify the reliability of the optimization results. This paper has positive significance for the variably accelerated improvement on a traditional PS algorithms. It can speed up TMD damping optimization calculation convergence rate under a premise of ensuring the optimization effect.The optimal parameter combination of a 3-TMD system obtained by a VAPS algorithm based on Den Hartog initial value has a displacement damping ratio of 39.2%, an increases of 10.7% compared to a single variable optimization based on a Den Hartog formula.Large-scale unconstrained optimization for MTMD systems become feasible via VAPS algorithm computational efficiency improvements due to optimizing calculation time which exponentially increases with the number of its TMD components.S1 Appendix(DOCX)Click here for additional data file.