Templateâ based protein structure prediction in CASP11 and retrospect of Iâ TASSER in the last decade

We report the structure prediction results of a new composite pipeline for templateâ based modeling (TBM) in the 11th CASP experiment. Starting from multiple structure templates identified by LOMETS based metaâ threading programs, the QUARK ab initio folding program is extended to generate initial fullâ length models under strong constraints from template alignments. The final atomic models are then constructed by Iâ TASSER based fragment reassembly simulations, followed by the fragmentâ guided molecular dynamic simulation and the MQAPâ based model selection. It was found that the inclusion of QUARKâ TBM simulations as an intermediate modeling step could help improve the quality of the Iâ TASSER models for both Easy and Hard TBM targets. Overall, the average TMâ score of the first Iâ TASSER model is 12% higher than that of the best LOMETS templates, with the RMSD in the same threadingâ aligned regions reduced from 5.8 to 4.7 à . Nevertheless, there are nearly 18% of TBM domains with the templates deteriorated by the structure assembly pipeline, which may be attributed to the errors of secondary structure and domain orientation predictions that propagate through and degrade the procedures of template identification and final model selections. To examine the record of progress, we made a retrospective report of the Iâ TASSER pipeline in the last five CASP experiments (CASP7â 11). The data show no clear progress of the LOMETS threading programs over PSIâ BLAST; but obvious progress on structural improvement relative to threading templates was witnessed in recent CASP experiments, which is probably attributed to the integration of the extended ab initio folding simulation with the threading assembly pipeline and the introduction of atomicâ level structure refinements following the reduced modeling simulations. Proteins 2016; 84(Suppl 1):233â 246. © 2015 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134137/1/prot24918.pd

China’s 10-year progress in DC gas-insulated equipment: From basic research to industry perspective

The construction of the future energy structure of China under the 2050 carbon-neutral vision requires compact direct current (DC) gas-insulation equipment as important nodes and solutions to support electric power transmission and distribution of long-distance and large-capacity. This paper reviews China's 10-year progress in DC gas-insulated equipment. Important progresses in basic research and industry perspective are presented, with related scientific issues and technical bottlenecks being discussed. The progress in DC gas-insulated equipment worldwide (Europe, Japan, America) is also reported briefly

Assessment of Metal Flow Balance in Multi-Output Porthole Hot Extrusion of AA6060 Thin-Walled Profile

For the porthole hot extrusion of a thin-walled tube based on metal flow, the role of the die’s structure should be focused on to achieve precision formation, especially for multi-output extrusion and/or complex cross-sectional profiles. In order to obtain a better metal flow balance, a multi-output porthole extrusion die was developed, including some novel features such as a circular pattern of the portholes with a dart-shaped inlet bridge, a buckle angle in the inlet side of the upper die, a two-step welding chamber, and a non-uniform bearing length distribution. Through the use of thermo-mechanical modeling combined with the Taguchi method, the underlying effects of key die features were investigated, such as the billet buckle angle, the porthole bevel angle, the depth of the welding chamber, and the type of bridge on the metal flow balance. The experimental validation showed that the developed numerical model for the multi-output porthole extrusion process had high prediction accuracy, and was acceptable for use in an industrial extrusion with a complex section

Acupuncture in the Treatment of Abnormal Muscle Tone in Children with Cerebral Palsy: A Meta-Analysis

Objective. To analyse the clinical efficacy of acupuncture and routine treatment in improving dystonia in children with cerebral palsy. Method. The randomized controlled trials published from the establishment of the databases to August 2022 on acupuncture in the treatment of dystonia in children with cerebral palsy were collected and comprehensively searched in China national knowledge infrastructure (CNKI), weipu (VIP), Wanfang, SinoMed, PubMed, Excerpta medica database (EMBASE), and Cochrane Library. The literature was selected according to the established standards, the quality of the included studies was evaluated, the heterogeneity of the included studies was evaluated with the I2 test, and the appropriate model was selected for analysis. Sensitivity analysis was used to evaluate the reliability of the results, and a funnel plot was used to evaluate the publication bias. Results. Fifteen studies were included in the meta-analysis. The control group was treated with routine treatment and acupuncture combined with routine treatment. The outcome index showed that the effect in the treatment group was better: Modified Ashworth Scale score: −0.52, 95% confidence interval (CI) (−0.62 to −0.41), p<0.01. The treatment group showed reduced muscle tension to a greater extent (integral eletromyographic (iEMG) score: standard mean square deviation = −2.97, 95% CI (−4.87 to −1.06), p<0.01). The effective rate in the control group was 74.2% and that in the treatment group was 91.5%, odds ratio = 3.70, 95% CI (2.02–6.78), p<0.01. The funnel plot showed publication bias. Conclusion. Acupuncture combined with routine training could improve muscle tension abnormalities and improve the efficiency of clinical treatment

Additional file 3 of THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours

Additional file 2. The different expression gene set of GIST-T1 cells after THZ1 treatment by RNA-sequencing analysis

Additional file 2 of THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours

Additional file 1. The siRNA sequences and qRT-PCR primer sequences used in this research.

Signaling and expression for mitochondrial membrane proteins during left ventricular remodeling and contractile failure after myocardial infarction

AbstractOBJECTIVESThis study was conducted to test hypotheses stating that: 1) altered signaling for mitochondrial membrane proteins occurs during postinfarction remodeling, and 2) successful myocardial adaptation relates to promotion of specific mitochondrial membrane components.BACKGROUNDAbnormalities in high-energy phosphate content and limitations in adenosine 5′-triphosphate (ATP) synthesis rate occur during the transition to contractile failure from compensatory remodeling after left ventricular infarction. The adenine nucleotide translocator (ANT) and F1-ATPase respectively regulate mitochondrial adenosine 5′-diphosphate (ADP)/ATP exchange and ADP-phosphorylation, which are key components of high-energy phosphate metabolism.METHODSSteady-state mRNA and protein expression for ANT isoform1 and the beta subunit of the F1-ATPase (betaF1) were analyzed in myocardium remote from the infarction zone eight weeks after left circumflex coronary artery ligation in pigs, demonstrating either successful left ventricular remodeling (LVR, n = 8) or congestive heart failure (CHF, n = 4) as determined by clinical and contractile performance parameters.RESULTSSubstantial reductions in steady-state mRNA expression for ANT1 and betaF1 relative to normal (n = 8) occur in CHF, p < 0.01, but not in LVR. Relative expression for both proteins coordinated with their respective steady-state mRNA levels; CHF at 40% normal, p < 0.05 for ANT and 70% normal for betaF1, p < 0.05.CONCLUSIONSMaintained signaling for major mitochondrial membrane proteins occurs in association with successful remodeling and adaptation after infarction. Reduced expression of these proteins relates to limited ATP synthesis capacity and high energy phosphate kinetic abnormalities previously demonstrated in CHF. These findings imply that mitochondrial processes participate in myocardial remodeling after infarction

Integration of QUARK and Iâ TASSER for Ab Initio Protein Structure Prediction in CASP11

We tested two pipelines developed for templateâ free protein structure prediction in the CASP11 experiment. First, the QUARK pipeline constructs structure models by reassembling fragments of continuously distributed lengths excised from unrelated proteins. Five freeâ modeling (FM) targets have the model successfully constructed by QUARK with a TMâ score above 0.4, including the first model of T0837â D1, which has a TMâ scoreâ =â 0.736 and RMSDâ =â 2.9 à to the native. Detailed analysis showed that the success is partly attributed to the highâ resolution contact map prediction derived from fragmentâ based distanceâ profiles, which are mainly located between regular secondary structure elements and loops/turns and help guide the orientation of secondary structure assembly. In the Zhangâ Server pipeline, weakly scoring threading templates are reâ ordered by the structural similarity to the ab initio folding models, which are then reassembled by Iâ TASSER based structure assembly simulations; 60% more domains with length up to 204 residues, compared to the QUARK pipeline, were successfully modeled by the Iâ TASSER pipeline with a TMâ score above 0.4. The robustness of the Iâ TASSER pipeline can stem from the composite fragmentâ assembly simulations that combine structures from both ab initio folding and threading template refinements. Despite the promising cases, challenges still exist in longâ range betaâ strand folding, domain parsing, and the uncertainty of secondary structure prediction; the latter of which was found to affect nearly all aspects of FM structure predictions, from fragment identification, target classification, structure assembly, to final model selection. Significant efforts are needed to solve these problems before real progress on FM could be made. Proteins 2016; 84(Suppl 1):76â 86. © 2015 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134068/1/prot24930.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134068/2/prot24930_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134068/3/prot24930-sup-0001-suppinfo01.pd