Miracle-dz/UniFAR-FTUs huggingface dataset:
Patterns of Polymorphism at the Self-Incompatibility Locus in 1,083 Arabidopsis thaliana Genomes

Although the transition to selfing in the model plant Arabidopsis thaliana involved the loss of the self-incompatibility (SI) system, it clearly did not occur due to the fixation of a single inactivating mutation at the locus determining the specificities of SI (the S-locus). At least three groups of divergent haplotypes (haplogroups), corresponding to ancient functional S-alleles, have been maintained at this locus, and extensive functional studies have shown that all three carry distinct inactivating mutations. However, the historical process of loss of SI is not well understood, in particular its relation with the last glaciation. Here, we took advantage of recently published genomic re-sequencing data in 1,083 Arabidopsis thaliana accessions that we combined with BAC sequencing to obtain polymorphism information for the whole S-locus region at a species-wide scale. The accessions differed by several major rearrangements including large deletions and inter-haplogroup recombinations, forming a set of haplogroups that are widely distributed throughout the native range and largely overlap geographically. ‘Relict’ A. thaliana accessions that directly derive from glacial refugia are polymorphic at the S-locus, suggesting that the three haplogroups were already present when glacial refugia from the last Ice Age became isolated. Inter-haplogroup recombinant haplotypes were highly frequent, and detailed analysis of recombination breakpoints suggested multiple independent origins. These findings suggest that the complete loss of SI in A. thaliana involved independent self-compatible mutants that arose prior to the last Ice Age, and experienced further rearrangements during post-glacial colonization.
S100A9 induces monocyte/ macrophage migration via EMMPRIN

Vasileia Ismini Alexaki1; Andreas E. May2,3; Chika Fujii1; Saskia N. I. v. UngernSternberg2; Christine Mund1; Meinrad Gawaz2; Triantafyllos Chavakis1*; Peter Seizer2* 1Department of Clinical Pathobiochemistry, Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technische Universität Dresden, Dresden, Germany; 2Medizinische Klinik III, Universitätsklinikum Tübingen, Tübingen, Germany; 3Medizinische Klinik I, Klinikum Memmingen, Memmingen, Germany
A human leucyl-tRNA synthetase as an anticancer target

Several aminoacyl-tRNA synthetases have been reported to be overexpressed for charging essential aminoacyl-tRNAs in many cancer types. In this study, we aimed to explore the potential role of leucyl-tRNA synthetase (LARS) as an anticancer target. MTT assay was performed to screen inhibitors to human LARS (hsLARS) from compounds AN2690 and its derivatives, compounds 1–6, in U2OS and SKOV3 cells. The compound with the strongest inhibitory ability was further investigated for its inhibitory effect in cancer cell lines and in an animal tumor model. Additionally, a LARS-rescue experiment was performed to explore the potential target in U2OS using Western blot and flow cytometry. Luciferase reporter assay was designed to analyze the effect of of hsLARS inhibitor on p21 activation. We identified an hsLARS inhibitor (compound 2) that suppressed the proliferation of U2OS and SKOV3 cells in vitro. A LARS-rescue experiment demonstrated that the proliferation inhibition was induced by targeting intracellular LARS. In addition, the hsLARS inhibition was shown to activate the p21 early transcription and promote cell apoptosis, as well as reduce implanted EMT6 tumor progression in mice. Our results suggest that LARS might serve as a potential anticancer target through the p21 signaling pathway and that the nutritional signaling pathway may provide a valuable anticancer strategy for further investigation.
Microstructure and wear resistance of TiCN-reinforced Co matrix coatings on tool steel

TiCN-reinforced Co alloy coatings were successfully fabricated on H13 steel by laser cladding. The microstructure and wear properties at room temperature were investigated. The results showed that the coatings are free of defects with sound metallurgical bonding to H13 substrate. The average microhardness of TiCN-reinforced Co alloy coatings with different contents of TiCN was more than twice to three times that of the H13 steel. The laser clad TiCN-reinforced Co alloy coatings exhibited good friction-reducing and antiwear abilities at room temperature. The composite coating significantly decreased wear weight loss and wear rate as the weight fraction of TiCN increased. TiCN-reinforced Co alloy coatings with smooth worn surface were characterised by mild adhesion wear and slight plastic deformation.
Cytochrome P450 3A Induction Predicts P‐glycoprotein Induction; Part 2: Prediction of Decreased Substrate Exposure After Rifabutin or Carbamazepine

Rifampin demonstrated dose‐dependent relative induction between cytochrome P (CYP)3A and P‐glycoprotein (P‐gp), organic anion transporting polypeptides (OATPs), or CYP2C9; P‐gp, OATP, and CYP2C9 induction was one drug–drug interaction (DDI) category lower than that observed for CYP3A across a wide range of pregnane X receptor (PXR) agonism. The objective of this study was to determine if these relationships could be utilized to predict transporter induction by other CYP3A inducers (rifabutin and carbamazepine) and of another P‐gp substrate, sofosbuvir. Healthy subjects received sofosbuvir and a six‐probe drug cassette before and after 300 mg q.d. rifabutin or 300 mg b.i. d. carbamazepine. Induction of P‐gp, CYP2C9, and decreased sofosbuvir exposure were successfully predicted by observed CYP3A induction. Carbamazepine induction of OATP was underpredicted, likely due to reported additional non‐PXR agonism. The results demonstrate that the effect of a PXR agonist on CYP3A can be leveraged to inform on induction liability for other primarily PXR‐regulated P450s/transporters, allowing for prioritization of targeted DDI assessments during new drug development.
Two-Temperature Continuum Model for Metal Plasticity

A physically based continuum plasticity model for metals from the consideration of non-equilibrium thermodynamics is presented. The modeling is accomplished in a two-temperature framework that appears naturally by considering the thermodynamic system to be composed of two weakly interacting subsystems, namely the kinetic vibrational and configurational subsystems. While the atomic vibrations of plastically deforming metals form the kinetic vibrational subsystem, much slower degrees of freedom in terms of the motion of defects constitute the configurational subsystem. Both subsystems assume their own temperatures and fall out of equilibrium from each other because of the externally imposed driving. Dislocation density characterising the configurational subsystem is considered to be the state variable for the present development. The continuum model accommodates finite deformation and describes plastic deformation in a yield-free framework via a microforce balance along with the conventional macroforce balance.
Characterization of muscles associated with the articular membrane in the dorsal surface of the crayfish abdomen.

The anatomy, physiology, and biochemistry of the dorsal membrane muscle (DMA) and the superficial extensor muscle accessory head (SEAcc) in the abdomen of the crayfish, Procambarus clarkii and lobster, Homarus americanus, are reported. These muscles have not been previously characterized physiologically or biochemically. The anatomy was originally described by Pilgrim and Wiersma (1963. J Morph 113:453-587). The arrangement of these muscles varies depending on the abdominal segment. The function of the dorsal membrane muscle is to retract the thin articulating membrane joining the cuticular segments so that the dorsal membrane does not evert during extension of the abdomen. Consequently, the articular membrane does not protrude, and thus potential damage to the membrane is minimized. Examination of nerve terminal morphology revealed strings of varicosities, usually only associated with tonic terminals. The electrophysiological data indicate that there are at least four tonic excitatory and one inhibitory motor neuron innervating these muscles. Facilitation indices and fatigue-resistance indicate physiologically the tonic nature of innervation. Anti-GABA antibodies demonstrate the anatomical presence of an inhibitor motor neuron. The SDS electrophoretic analysis of myofibrillar proteins and Western blots of key protein isoforms for these muscles in crayfish and lobsters also indicate that the DMA and SEAcc muscles are tonic phenotype. J. Exp. Zool. 287:353-377, 2000.
PRIMA‐1 induces p53‐mediated apoptosis by upregulating Noxa in esophageal squamous cell carcinoma with TP53 missense mutation

TP53 is associated with the resistance of cytotoxic treatment and patient prognosis, and the mutation rate of TP53 in esophageal squamous cell carcinoma (ESCC) is extraordinarily high, at over 90%. PRIMA‐1 (p53 re‐activation and induction of massive apoptosis) has recently been reported to restore the function of mutant TP53; however, its antitumor effect and mechanism in ESCC remain unclear. After evaluating the TP53 mutation status of a panel of 11 ESCC cell lines by Sanger sequencing, we assessed the in vitro effect of PRIMA‐1 administration on cells with different TP53 status by conducting cell viability and apoptosis assays. The expression levels of proteins in p53‐related pathways were examined by Western blotting, while knockdown studies were conducted to investigate the mechanism underlying PRIMA‐1's function. An ESCC xenograft model was further used to evaluate the therapeutic effect of PRIMA‐1 in vivo. PRIMA‐1 markedly inhibited cell growth and induced apoptosis by upregulating Noxa expression in ESCC cell lines with TP53 missense mutations, whereas no apoptosis was induced in ESCC with wild‐type TP53 and TP53 with frameshift and nonsense mutations. Importantly, the knockdown of Noxa canceled the apoptosis induced by PRIMA treatment in ESCC cell lines with TP53 missense mutations. PRIMA‐1 administration, compared with placebo, showed a significant antitumor effect by inducing Noxa in the xenograft model of an ESCC cell line with a TP53 missense mutation. PRIMA‐1 exhibits a significant antitumor effect, inducing massive apoptosis through the upregulation of Noxa in ESCC with TP53 missense mutations.
CSE 599 i : Online and Adaptive Machine Learning Winter 2018 Lecture 19 : Monte Carlo Tree Search

Monte Carlo Tree Search (MCTS) is a policy-optimization algorithm for finite-horizon, finite-size Markov Decision Processes, based on random episode sampling structured by a decision tree [1]. In this section, we describe Monte Carlo Tree Search in generality, laying the groundwork for the bandit-based extension discussed in the following section. As a preview, that extension essentially provides an effective yet still generic instantiation, with proven probabilistic guarantees, for an especially challenging implementationspecific component of MCTS.
NEURAL NETWORK SIMULATIONS OF CONFINED CONCRETE CIRCULAR COLUMNS

An artificial neural network (ANN) model for predicting the confined compressive strength and corresponding strain of circular concrete columns was used to simulate the effect of various parameters on confinement. The ANN model with seven input parameters - unconfined compressive strength of concrete, core diameter, column height, yield strength of lateral reinforcement, volumetric ratio of lateral reinforcement, tie spacing and longitudinal steel ratio - was used for parametric studies to understand qualitatively the effect of the input parameters on the confined compressive strength and strain at peak axial stress of circular columns. The study showed the potential of ANNs in modeling, prediction and in simulating physical processes such as confined behavior of concrete circular columns.
Therapeutic Potentials of “ Shilajit Rasayana ”-A Review

Shilajit is a rejuvenator (‘Rasayana’) of traditional Hindu Ayurvedic origin, which clearly has attracted considerable interest in India. Shilajit is a blackish-brown exudation of variable consistency exuding from layers of rocks in many mountain ranges of the world, especially the Himalayas and Hindukush ranges of the Indian subcontinent. Shilajit has been used as a folk medicine for general physical strengthening, anti-aging, blood sugar stabilization, urinary tract rejuvenation, enhanced brain functioning potency, kidney rejuvenation, immune system strengthening, arthritis, hypertension as well as for treating many other conditions. Shilajit (botanical name: Asphaltum), also known as mineral pitch, is a natural exudate oozed from rocks during hot weather. Shilajit is a compact mass of vegetable organic matter, which is composed of a gummy matrix interspersed with vegetable fibers and minerals.
Proteomics Indicators of the Rapidly Shifting Physiology from Whole Mountain Pine Beetle, Dendroctonus ponderosae (Coleoptera: Curculionidae), Adults during Early Host Colonization

We developed proteome profiles for host colonizing mountain pine beetle adults, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae). Adult insects were fed in pairs on fresh host lodgepole pine, Pinus contorta Dougl. ex Loud, phloem tissue. The proteomes of fed individuals were monitored using iTRAQ and compared to those of starved beetles, revealing 757 and 739 expressed proteins in females and males, respectively, for which quantitative information was obtained. Overall functional category distributions were similar for males and females, with the majority of proteins falling under carbohydrate metabolism (glycolysis, gluconeogenesis, citric acid cycle), structure (cuticle, muscle, cytoskeleton), and protein and amino acid metabolism. Females had 23 proteins with levels that changed significantly with feeding (p<0.05, FDR<0.20), including chaperones and enzymes required for vitellogenesis. In males, levels of 29 proteins changed significantly with feeding (p<0.05, FDR<0.20), including chaperones as well as motor proteins. Only two proteins, both chaperones, exhibited a significant change in both females and males with feeding. Proteins with differential accumulation patterns in females exhibited higher fold changes with feeding than did those in males. This difference may be due to major and rapid physiological changes occurring in females upon finding a host tree during the physiological shift from dispersal to reproduction. The significant accumulation of chaperone proteins, a cytochrome P450, and a glutathione S-transferase, indicate secondary metabolite-induced stress physiology related to chemical detoxification during early host colonization. The females' activation of vitellogenin only after encountering a host indicates deliberate partitioning of resources and a balancing of the needs of dispersal and reproduction.
Improving Genomic Prediction in Cassava Field Experiments by Accounting for Interplot Competition

Plants competing for available resources is an unavoidable phenomenon in a field. We conducted studies in cassava (Manihot esculenta Crantz) in order to understand the pattern of this competition. Taking into account the competitive ability of genotypes while selecting parents for breeding advancement or commercialization can be very useful. We assumed that competition could occur at two levels: (i) the genotypic level, which we call interclonal, and (ii) the plot level irrespective of the type of genotype, which we call interplot competition or competition error. Modification in incidence matrices was applied in order to relate neighboring genotype/plot to the performance of a target genotype/plot with respect to its competitive ability. This was added into a genomic selection (GS) model to simultaneously predict the direct and competitive ability of a genotype. Predictability of the models was tested through a 10-fold cross-validation method repeated five times. The best model was chosen as the one with the lowest prediction root mean squared error (pRMSE) compared to that of the base model having no competitive component. Results from our real data studies indicated that <10% increase in accuracy was achieved with GS-interclonal competition model, but this value reached up to 25% with a GS-competition error model. We also found that the competitive influence of a cassava clone is not just limited to the adjacent neighbors but spreads beyond them. Through simulations, we found that a 26% increase of accuracy in estimating trait genotypic effect can be achieved even in the presence of high competitive variance.
MetaExp: Interactive Explanation and Exploration of Large Knowledge Graphs

We present MetaExp, a system that assists the user during the exploration of large knowledge graphs, given two sets of initial nodes. At its core, MetaExp presents a small set of meta-paths to the user, which are sequences of relationships among node types. Such meta-paths do not overwhelm the user with complex structures, yet they preserve semantically-rich relationships in a graph. MetaExp engages the user in an interactive procedure, which involves simple meta-paths evaluations to infer a user-specific similarity measure. This similarity measure incorporates the domain knowledge and the preferences of the user, overcoming the fundamental limitations of previous methods based on local node neighborhoods or statically determined similarity scores. Our system provides a user-friendly interface for searching initial nodes and guides the user towards progressive refinements of the meta-paths. The system is demonstrated on three datasets, Freebase, a movie database, and a biological network.
Interaction of synchronized dynamics in cortex and basal ganglia in Parkinson's disease

Parkinson's disease pathophysiology is marked by increased oscillatory and synchronous activity in the beta frequency band in cortical and basal ganglia circuits. This study explores the functional connections between synchronized dynamics of cortical areas and synchronized dynamics of subcortical areas in Parkinson's disease. We simultaneously recorded neuronal units (spikes) and local field potentials (LFP) from subthalamic nucleus (STN) and electroencephalograms (EEGs) from the scalp in parkinsonian patients, and analysed the correlation between the time courses of the spike–LFP synchronization and inter‐electrode EEG synchronization. We found the (non‐invasively obtained) time course of the synchrony strength between EEG electrodes and the (invasively obtained) time course of the synchrony between spiking units and LFP in STN to be weakly, but significantly, correlated with each other. This correlation is largest for the bilateral motor EEG synchronization, followed by bilateral frontal EEG synchronization. Our observations suggest that there may be multiple functional modes by which the cortical and basal ganglia circuits interact with each other in Parkinson's disease: not only may synchronization be observed between some areas in cortex and the basal ganglia, but also synchronization within cortex and within basal ganglia may be related, suggesting potentially a more global functional interaction. More coherent dynamics in one brain region may modulate or activate the dynamics of another brain region in a more powerful way, causing correlations between changes in synchrony strength in the two regions.
Hierarchical priors for bias parameters in Bayesian sensitivity analysis for unmeasured confounding

Recent years have witnessed new innovation in Bayesian techniques to adjust for unmeasured confounding. A challenge with existing methods is that the user is often required to elicit prior distributions for high‐dimensional parameters that model competing bias scenarios. This can render the methods unwieldy. In this paper, we propose a novel methodology to adjust for unmeasured confounding that derives default priors for bias parameters for observational studies with binary covariates. The confounding effects of measured and unmeasured variables are treated as exchangeable within a Bayesian framework. We model the joint distribution of covariates by using a log‐linear model with pairwise interaction terms. Hierarchical priors constrain the magnitude and direction of bias parameters. An appealing property of the method is that the conditional distribution of the unmeasured confounder follows a logistic model, giving a simple equivalence with previously proposed methods. We apply the method in a data example from pharmacoepidemiology and explore the impact of different priors for bias parameters on the analysis results. Copyright © 2011 John Wiley & Sons, Ltd.
Women’s Ideas about the Health Effects of Household Air Pollution, Developed through Focus Group Discussions and Artwork in Southern Nepal

Household air pollution is a major cause of ill health, but few solutions have been effective to date. While many quantitative studies have been conducted, few have explored the lived experiences and perceptions of women who do the cooking, and as a result are those most exposed to household air pollution. In this study, we worked with groups of home cooks, and sought to use art as a means of engaging them in discussions of how household air pollution from cooking affects their lives. In the Terai district of southern Nepal, we held four focus groups that included 26 local women from urban and peri-urban areas, as well as six local artists. The women then met approximately weekly over four months, and produced images related to air pollution. Transcripts from the focus groups were reviewed independently by two authors, who initially categorised data deductively to pre-defined nodes, and subsequently inductively reviewed emergent themes. Women identified a number of health effects from air pollution. The main physical effects related to the eye and the respiratory system, and women and young children were seen as most vulnerable. The psychosocial effects of air pollution included reduced food intake by women and lethargy. Suggested solutions included modifications to the cooking process, changing the location of stoves, and increasing ventilation. The main barriers were financial. The lived experiences of women in southern Nepal around the problem of air pollution offers a more nuanced and context-specific understanding of the perceptions and challenges of addressing air pollution, which can be used to inform future interventions.
Preparation and properties of compatibilized PVC/SMA‐g‐PA6 blends

The morphology and mechanical properties of PVC/SMA-g-PA6 blends were investigated in this paper. Graft to polymer SMA-g-PA6 was prepared via a solution graft reaction between SMA and PA6. FTIR test evidences the occurrence of the graft reaction between SMA and PA6. DSC analysis shows that SMA-g-PA6 has a lower melting point of 187°C, which may result in a decrease in crystallinity of PA6 and thus enable efficient blending of SMA-g-PA6 and PVC. Compatibilization was evidenced by the dramatic increase in mechanical properties, the smaller particle size and finer dispersion of PA6 in PVC matrix, and, further, a cocontinuous morphology at 16 wt % SMA-g-PA6 content. SMA-g-PA6 from the solution graft reaction can toughen and reinforce PVC material. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 432–439, 2004