Miracle-dz/UniFAR-FTUs huggingface dataset:
TMPad: an integrated structural database for helix-packing folds in transmembrane proteins

α-Helical transmembrane (TM) proteins play an important role in many critical and diverse biological processes, and specific associations between TM helices are important determinants for membrane protein folding, dynamics and function. In order to gain insights into the above phenomena, it is necessary to investigate different types of helix-packing modes and interactions. However, such information is difficult to obtain because of the experimental impediment and a lack of a well-annotated source of helix-packing folds in TM proteins. We have developed the TMPad (TransMembrane Protein Helix-Packing Database) which addresses the above issues by integrating experimentally observed helix–helix interactions and related structural information of membrane proteins. Specifically, the TMPad offers pre-calculated geometric descriptors at the helix-packing interface including residue backbone/side-chain contacts, interhelical distances and crossing angles, helical translational shifts and rotational angles. The TMPad also includes the corresponding sequence, topology, lipid accessibility, ligand-binding information and supports structural classification, schematic diagrams and visualization of the above structural features of TM helix-packing. Through detailed annotations and visualizations of helix-packing, this online resource can serve as an information gateway for deciphering the relationship between helix–helix interactions and higher levels of organization in TM protein structure and function. The website of the TMPad is freely accessible to the public at http://bio-cluster.iis. sinica.edu. tw/TMPad.
Beneficial Effects of Trimetazidine in Ex Vivo Working Ischemic Hearts Are Due to a Stimulation of Glucose Oxidation Secondary to Inhibition of Long-Chain 3-Ketoacyl Coenzyme A Thiolase

Abstract— High rates of fatty acid oxidation in the heart and subsequent inhibition of glucose oxidation contributes to the severity of myocardial ischemia. These adverse effects of fatty acids can be overcome by stimulating glucose oxidation, either directly or secondary to an inhibition of fatty acid oxidation. We recently demonstrated that trimetazidine stimulates glucose oxidation in the heart secondary to inhibition of fatty acid oxidation. This inhibition of fatty acid oxidation was attributed to an inhibition of mitochondrial long-chain 3-ketoacyl CoA thiolase (LC 3-KAT), an enzyme of fatty acid &bgr;-oxidation. However, the accompanying Research Commentary of MacInnes et al suggests that trimetazidine does not inhibit cardiac LC 3-KAT. This discrepancy with our data can be attributed to the reversible competitive nature of trimetazidine inhibition of LC 3-KAT. In the presence of 2.5 &mgr;mol/L 3-keto-hexadecanoyl CoA (KHCoA), trimetazidine resulted in a 50% inhibition of LC-3-KAT activity. However, the inhibition of LC 3-KAT could be completely reversed by increasing substrate (3-keto-hexadecanoyl CoA, KHCoA) concentrations to 15 &mgr;mol/L even at high concentrations of trimetazidine (100 &mgr;mol/L). The study of MacInnes et al was performed using concentrations of 3K-HCoA in excess of 16 &mgr;mol/L, a concentration that would completely overcome 100 &mgr;mol/L trimetazidine inhibition of LC 3-KAT. Therefore, the lack of inhibition of LC 3-KAT by trimetazidine in the MacInnes et al study can easily be explained by the high concentration of KHCoA substrate used in their experiments. In isolated working hearts perfused with high levels of fatty acids, we found that trimetazidine (100 &mgr;mol/L) significantly improves functional recovery of hearts subjected to a 30-minute period of global no-flow ischemia. This occurred in the absence of changes in oxygen consumption resulting in an improved increase in cardiac efficiency. Combined with our previous studies, we conclude that trimetazidine inhibition of LC 3-KAT decreases fatty acid oxidation and stimulates glucose oxidation, resulting in an improvement in cardiac function and efficiency after ischemia. The full text of this article is available online at http://www.circresaha. org.
I-vectors in the context of phonetically-constrained short utterances for speaker verification

Short speech duration remains a critical factor of performance degradation when deploying a speaker verification system. To overcome this difficulty, a large number of commercial applications impose the use of fixed pass-phrases. In this context, we show that the performance of the popular i-vector approach can be greatly improved by taking advantage of the phonetic information that they convey. Moreover, as i-vectors require a conditioning process to reach high accuracy, we show that further improvements are possible by taking advantage of this phonetic information within the normalisation process. We compare two methods, Within Class Covariance Normalization (WCCN) and Eigen Factor Radial (EFR), both relying on parameters estimated on the same development data. Our study suggests that WCCN is more robust to data mismatch but less efficient than EFR when the development data has a better match with the test data.
Co-expression of G2-EPSPS and glyphosate acetyltransferase GAT genes conferring high tolerance to glyphosate in soybean

Glyphosate is a widely used non-selective herbicide with broad spectrum of weed control around the world. At present, most of the commercial glyphosate tolerant soybeans utilize glyphosate tolerant gene CP4-EPSPS or glyphosate acetyltransferase gene GAT separately. In this study, both glyphosate tolerant gene G2-EPSPS and glyphosate degraded gene GAT were co-transferred into soybean and transgenic plants showed high tolerance to glyphosate. Molecular analysis including PCR, Sothern blot, qRT-PCR, and Western blot revealed that target genes have been integrated into genome and expressed effectively at both mRNA and protein levels. Furthermore, the glyphosate tolerance analysis showed that no typical symptom was observed when compared with a glyphosate tolerant line HJ06-698 derived from GR1 transgenic soybean even at fourfold labeled rate of Roundup. Chlorophyll and shikimic acid content analysis of transgenic plant also revealed that these two indexes were not significantly altered after glyphosate application. These results indicated that co-expression of G2-EPSPS and GAT conferred high tolerance to the herbicide glyphosate in soybean. Therefore, combination of tolerant and degraded genes provides a new strategy for developing glyphosate tolerant transgenic crops.
Effect of Stitching on the Static and Fatigue Performance of Co-Cured Composite Single-Lap Joints

The paper investigates the effect of Kevlar stitching on the tensile static and fatigue properties of co-cured single-lap joints with cross-ply graphite- epoxy adherends. The variables considered in this study were the overlap length, the stitch spacing, and the off-edge distance. Experimental results indicate that while stitching does not improve the static strength, stitched joints exhibit much better fatigue performance than unstitched joints. Ultrasonic analyses and continuous monitoring of stiffness change during fatigue life allowed us to follow delamination progression and to clearly identify the nucleation and the propagation stages, in particular, stitching was observed to increase the durations of both the crack initiation and crack propagation phases, with stitches remaining intact until complete failure. Moreover, in the range of values examined, the fatigue behavior of stitched joints is improved by reducing the stitch spacing, while it appears to be insensitive to the variation of the off-edge distance of stitches.
Some Basic Aspects of HLA-G Biology

Human leukocyte antigen-G (HLA-G) is a low polymorphic nonclassical HLA-I molecule restrictively expressed and with suppressive functions. HLA-G gene products are quite complex, with seven HLA-G isoforms, four membrane bound, and other three soluble isoforms that can suffer different posttranslational modifications or even complex formations. In addition, HLA-G has been described included in exosomes. In this review we will focus on HLA-G biochemistry with special emphasis to the mechanisms that regulate its expression and how the protein modifications affect the quantification in biological fluids.
Signal Transducer and Activator of Transcription 6 Is Essential in the Induction of Contact Hypersensitivity

Contact hypersensitivity (CHS) is thought to be mainly associated with the activation of T helper type 1 (Th1) cells. However, there is also evidence that Th2 cells or Th2 cytokines play a role in the development of CHS. To analyze the functional contribution of Th2 cytokines interleukin (IL)-4 and IL-13, signal transducer and activator of transcription 6 (STAT6)-deficient (STAT6−/−) and wild-type (wt) control C57BL/6 mice were contact sensitized with 5% 2,4,6-trinitrochlorobenzene (TNCB), 0.5% 2,4-dinitrofluorobenzene, or 5% 4-ethoxyl methylene-2-phenyl-2-oxazolin-5-one, and any skin reactions were examined. Ear swelling was significantly reduced with a delayed peak response in STAT6−/− mice compared with wt mice. A histological analysis revealed that the infiltration of both eosinophils and neutrophils in the skin challenged after 24 h in STAT6−/− mice decreased substantially compared with that in wt mice. The expression of Th2 cytokines (IL-4, IL-5) in TNCB-challenged skin tissues and the supernatants from T cells stimulated by 2,4,6-trinitrobenzene sulfonate–modified spleen cells, as well as the immunoglobulin (Ig)E and IgG1 response after challenge, were also profoundly reduced in STAT6−/− mice, whereas the expression of interferon γ was the same in STAT6−/− and wt mice after challenge. Furthermore, adoptive transfer experiments revealed that STAT6−/− mice induced CHS after injection of lymph node cells obtained from sensitized wt mice. Our data suggest that the STAT6 signal plays a critical role in the induction phase of CHS.
An Experimental Study on Automatic Face Gender Classification

This paper presents an experimental study on automatic face gender classification by building a system that mainly consists of four parts, face detection, face alignment, texture normalization and gender classification. Comparative study on the effects of different texture normalization methods including two kinds of affine mapping and one Delaunay triangulation based warping as preprocesses for gender classification by SVM, LDA and real Adaboost respectively is reported through experiments on very large sets of snapshot images
High Thyroglobulin Antibody Levels Increase the Risk of Differentiated Thyroid Carcinoma

Background. Despite the many studies examining thyroid cancers, the effect of thyroid autoantibodies on differentiated thyroid carcinoma (DTC) remains unclear. Objective. To investigate the association between serologic thyroid autoantibodies (ATAs) and DTC, we retrospectively evaluated data of thyroid nodules obtained from patients who underwent thyroid surgery. Methods. Data of thyroid nodules obtained from 1,638 patients who underwent thyroid surgery were evaluated. Thyroid autoimmunity was assessed by the presence of thyroglobulin (TgAb) or thyroid peroxidase antibodies (TPOAb). Results. Among our study cohort, the prevalence of elevated TgAb (≥40 IU/mL) and TPOAb (≥50 IU/mL) was higher in patients with DTC than those with benign nodules. Patients with DTC and elevated TgAb had a higher prevalence of extrathyroidal invasion. In the multivariate analysis, TgAb ≥ 40 IU/mL was significantly associated with DTC (odds ratio [OR] = 2.10, 95% confidence interval [CI] 1.40–3.15) compared with TgAb < 40 IU/mL group, independent of other confounding factors such as decreased age, single nodule, and elevated TSH level. In conclusion, elevated TgAb was associated with DTC. Conclusions. This study revealed that high levels of TgAb may act as an independent prediction factor for DTC, and suggests that patients with high TgAb concentrations may be predisposed to DTC.
Exploiting Genomics Resources to Identify Candidate Genes Underlying Antioxidants Content in Tomato Fruit

The tomato is a model species for fleshy fruit development and ripening, as well as for genomics studies of others Solanaceae. Many genetic and genomics resources, including databases for sequencing, transcriptomics and metabolomics data, have been developed and are today available. The purpose of the present work was to uncover new genes and/or alleles that determine ascorbic acid and carotenoids accumulation, by exploiting one Solanum pennellii introgression lines (IL7-3) harboring quantitative trait loci (QTL) that increase the content of these metabolites in the fruit. The higher ascorbic acid and carotenoids content in IL7-3 was confirmed at three fruit developmental stages. The tomato genome reference sequence and the recently released S. pennellii genome sequence were investigated to identify candidate genes (CGs) that might control ascorbic acid and carotenoids accumulation. First of all, a refinement of the wild region borders in the IL7-3 was achieved by analyzing CAPS markers designed in our laboratory. Afterward, six CGs associated to ascorbic acid and one with carotenoids metabolism were identified exploring the annotation and the Gene Ontology terms of genes included in the region. Variants between the sequence of the wild and the cultivated alleles of these genes were investigated for their functional relevance and their potential effects on the protein sequences were predicted. Transcriptional levels of CGs in the introgression region were extracted from RNA-Seq data available for the entire S. pennellii introgression lines collection and verified by Real-Time qPCR. Finally, seven IL7-3 sub-lines were genotyped using 28 species-specific markers and then were evaluated for metabolites content. These analyses evidenced a significant decrease in transcript abundance for one 9-cis-epoxycarotenoid dioxygenase and one L-ascorbate oxidase homolog, whose role in the accumulation of carotenoids and ascorbic acid is discussed. Comprehensively, the reported results demonstrated that combining genetic and genomic resources in tomato, including bioinformatics tools, was a successful strategy to dissect one QTL for the increase of ascorbic acid and carotenoids in tomato fruit.
Zone and polygon menus: using relative position to increase the breadth of multi-stroke marking menus

We present Zone and Polygon menus, two new variants of multi-stroke marking menus that consider both the relative position and orientation of strokes. Our menus are designed to increase menu breadth over the 8 item limit of status quo orientation-based marking menus. An experiment shows that Zone and Polygon menus can successfully increase breadth by a factor of 2 or more over orientation-based marking menus, while maintaining high selection speed and accuracy. We also discuss hybrid techniques that may further increase menu breadth and performance. Our techniques offer UI designers new options for balancing menu breadth and depth against selection speed and accuracy.
Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide

ABSTRACT Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which upon absorption by the host is converted in the liver to trimethylamine-N-oxide (TMAO). Recent studies revealed that TMAO exacerbates atherosclerosis in mice and positively correlates with the severity of this disease in humans. However, which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., genotype) and diet affect TMA production and colonization of these microbes, and the effects TMA-producing microbes have on the bioavailability of dietary choline remain largely unknown. We screened a collection of 79 sequenced human intestinal isolates encompassing the major phyla found in the human gut and identified nine strains capable of producing TMA from choline in vitro. Gnotobiotic mouse studies showed that TMAO accumulates in the serum of animals colonized with TMA-producing species, but not in the serum of animals colonized with intestinal isolates that do not generate TMA from choline in vitro. Remarkably, low levels of colonization by TMA-producing bacteria significantly reduced choline levels available to the host. This effect was more pronounced as the abundance of TMA-producing bacteria increased. Our findings provide a framework for designing strategies aimed at changing the representation or activity of TMA-producing bacteria in the human gut and suggest that the TMA-producing status of the gut microbiota should be considered when making recommendations about choline intake requirements for humans. IMPORTANCE Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and increased trimethylamine N-oxide (TMAO) levels have been causally linked with CVD development. This work identifies members of the human gut microbiota responsible for both the accumulation of trimethylamine (TMA), the precursor of the proatherogenic compound TMAO, and subsequent decreased choline bioavailability to the host. Understanding how to manipulate the representation and function of choline-consuming, TMA-producing species in the intestinal microbiota could potentially lead to novel means for preventing or treating atherosclerosis and choline deficiency-associated diseases. Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and increased trimethylamine N-oxide (TMAO) levels have been causally linked with CVD development. This work identifies members of the human gut microbiota responsible for both the accumulation of trimethylamine (TMA), the precursor of the proatherogenic compound TMAO, and subsequent decreased choline bioavailability to the host. Understanding how to manipulate the representation and function of choline-consuming, TMA-producing species in the intestinal microbiota could potentially lead to novel means for preventing or treating atherosclerosis and choline deficiency-associated diseases.
The Eurasian Heartland: A continental perspective on Y-chromosome diversity

The nonrecombining portion of the human Y chromosome has proven to be a valuable tool for the study of population history. The maintenance of extended haplotypes characteristic of particular geographic regions, despite extensive admixture, allows complex demographic events to be deconstructed. In this study we report the frequencies of 23 Y-chromosome biallelic polymorphism haplotypes in 1,935 men from 49 Eurasian populations, with a particular focus on Central Asia. These haplotypes reveal traces of historical migrations, and provide an insight into the earliest patterns of settlement of anatomically modern humans on the Eurasian continent. Central Asia is revealed to be an important reservoir of genetic diversity, and the source of at least three major waves of migration leading into Europe, the Americas, and India. The genetic results are interpreted in the context of Eurasian linguistic patterns.
Sequential Intensification of Metformin Treatment in Type 2 Diabetes With Liraglutide Followed by Randomized Addition of Basal Insulin Prompted by A1C Targets

OBJECTIVE We evaluated the addition of liraglutide to metformin in type 2 diabetes followed by intensification with basal insulin (detemir) if glycated hemoglobin (A1C) ≥7%. RESEARCH DESIGN AND METHODS In 988 participants from North America and Europe uncontrolled on metformin ± sulfonylurea, sulfonylurea was discontinued and liraglutide 1.8 mg/day added for 12 weeks (run-in). Subsequently, those with A1C ≥7% were randomized 1:1 to 26 weeks’ open-label addition of insulin detemir to metformin + liraglutide (n = 162) or continuation without insulin detemir (n = 161). Patients achieving A1C <7% continued unchanged treatment (observational arm). The primary end point was A1C change between randomized groups. RESULTS Of 821 participants completing the run-in, 61% (n = 498) achieved A1C <7% (mean change −1.3% from 7.7% at start), whereas 39% (n = 323) did not (−0.6% from 8.3% at start). During run-in, 167 of 988 (17%) withdrew; 46% of these due to gastrointestinal adverse events. At week 26, A1C decreased further, by 0.5% (from 7.6% at randomization) with insulin detemir (n = 162) versus 0.02% increase without insulin detemir (n = 157) to 7.1 and 7.5%, respectively (estimated treatment difference −0.52 [95% CI −0.68 to −0.36]; P < 0.0001). Forty-three percent of participants with insulin detemir versus 17% without reached A1C <7%. Mean weight decreased by 3.5 kg during run-in, then by 0.16 kg with insulin detemir or 0.95 kg without insulin detemir. In the randomized phase, no major hypoglycemia occurred and minor hypoglycemia rates were 0.286 and 0.029 events per participant-year with and without insulin detemir (9.2 vs. 1.3%). CONCLUSIONS Supplementation of metformin with liraglutide and then insulin detemir was well tolerated in the majority of patients, with good glycemic control, sustained weight loss, and very low hypoglycemia rates.
Factors influencing blood pressure and heart rate variability in hypertensive humans.

We examined the influence of baroreceptor reflex sensitivity (the increase in pulse interval in response to a phenylephrine-induced increase in blood pressure), age, blood pressure, and beta-adrenergic receptor blockade on the variability of blood pressure and heart rate in essential hypertension. Fifty-six subjects were studied before treatment; intra-arterial blood pressure was recorded outside the hospital for 24 hours. Variability was defined (from all beats occurring while subjects were awake) as the standard deviation about the average waking value for mean arterial pressure (MAP) or pulse interval. The correlation (r) between baroreceptor reflex sensitivity and blood pressure variability was -0.47 (p less than 0.0002). Baroreceptor reflex sensitivity was the only independent determinant of blood pressure variability on multiple regression analysis. Thirty subjects were restudied after 5 months of beta-adrenergic receptor blockade. Ambulatory blood pressure was lower during treatment, whereas pulse interval, its variability, and baroreceptor reflex sensitivity were higher. Blood pressure variability was unchanged. The variability of MAP was inversely correlated with baroreceptor reflex sensitivity before (r = -0.42, p less than 0.02) and during (r = -0.45, p less than 0.02) treatment, but it was unrelated to the average ambulatory MAP or to the variability of pulse interval either before or during beta-blockade. Sixteen subjects whose average waking ambulatory blood pressure was 140/90 mm Hg or less were not treated. This group of borderline hypertensive subjects had less variable MAP than did the remaining 40 subjects (12.4 +/- 2.3 [SD] vs 14.5 +/- 2.5 mm Hg; p less than 0.01). (ABSTRACT TRUNCATED AT 250 WORDS)