Miracle-dz/UniFAR-FTUs huggingface dataset:
CYP2C8-Mediated Formation of a Human Disproportionate Metabolite of the Selective NaV1.7 Inhibitor DS-1971a, a Mixed Cytochrome P450 and Aldehyde Oxidase Substrate

Predicting human disproportionate metabolites is difficult, especially when drugs undergo species-specific metabolism mediated by cytochrome P450s (P450s) and/or non-P450 enzymes. This study assessed human metabolites of DS-1971a, a potent Nav1.7-selective blocker, by performing human mass balance studies and characterizing DS-1971a metabolites, in accordance with the Metabolites in Safety Testing guidance. In addition, we investigated the mechanism by which the major human disproportionate metabolite (M1) was formed. After oral administration of radiolabeled DS-1971a, the major metabolites in human plasma were P450-mediated monoxidized metabolites M1 and M2 with area under the curve ratios of 27% and 10% of total drug-related exposure, respectively; the minor metabolites were dioxidized metabolites produced by aldehyde oxidase and P450s. By comparing exposure levels of M1 and M2 between humans and safety assessment animals, M1 but not M2 was found to be a human disproportionate metabolite, requiring further characterization under the Metabolites in Safety Testing guidance. Incubation studies with human liver microsomes indicated that CYP2C8 was responsible for the formation of M1. Docking simulation indicated that, in the formation of M1 and M2, there would be hydrogen bonding and/or electrostatic interactions between the pyrimidine and sulfonamide moieties of DS-1971a and amino acid residues Ser100, Ile102, Ile106, Thr107, and Asn217 in CYP2C8, and that the cyclohexane ring of DS-1971a would be located near the heme iron of CYP2C8. These results clearly indicate that M1 is the predominant metabolite in humans and a human disproportionate metabolite due to species-specific differences in metabolism. SIGNIFICANCE STATEMENT This report is the first to show a human disproportionate metabolite generated by CYP2C8-mediated primary metabolism. We clearly demonstrate that DS-1971a, a mixed aldehyde oxidase and cytochrome P450 substrate, was predominantly metabolized by CYP2C8 to form M1, a human disproportionate metabolite. Species differences in the formation of M1 highlight the regio- and stereoselective metabolism by CYP2C8, and the proposed interaction between DS-1971a and CYP2C8 provides new knowledge of CYP2C8-mediated metabolism of cyclohexane-containing substrates.
A Stochastic Characterization Based Data Mining Implementation for Airport Arrival and Departure Delay Data

The probabilistic distribution of Airport arrival and departure delays over a selected period of eight months was analyzed using an optimal Generalized Extreme Value (GEV) model in this paper. It is anticipated that quantitative stochastic characterizations of delay data out of our work would improve demand predictions in air traffic flow management systems. Analysis and verification through application of Beijing Capital International Airport’s history flight delay data demonstrate better Goodness of Fit of our optimal GEV based model.
AN OPTIMIZATION APPROACH TO CAPACITY EXPANSION IN SEMICONDUCTOR MANUFACTURING FACILITIES

For a given demand and planning horizon, the general facility design problem faced by semiconductor manufacturers is to decide how much capacity to build into their systems. When the technology is known and only a small number of products is to be manufactured, the specific problem is to find a tool-set configuration that minimizes the average cycle time within a prescribed budget. In this paper, it is shown that this version of the capacity expansion problem can be modelled as a nonlinear integer program in which the decision variables correspond to the number of tools at a workstation. The major difficulty encountered in trying to find solutions is that no closed form expressions exist for the waiting time, primarily due to the presence of re-entrant flow. This means that it has to be approximated. At the outset, it was observed that previously proposed approximation methods based on parametric decomposition provided extremely poor results. In response, a new set of expressions, in the form of simultane.
Optimisation of rejection filters

The problem of separating unknown signals from much stronger ‘coloured’ noise often arises in radar receivers (m.t.i. cancellers) and antenna sytems (directive noise in phased-array antennas). Two main optimisation criteria can be used to design rejection filters, namely (i) the maximisation of average signal/interference ratio (based on the evaluation of the eigenvectors of the interference covariance matrix) and (ii) the linear prediction of interference samples (based on the solution of the normal-equations set). These two methods are compared in terms of algorithms complexity and improvement of signal/interference ratio. The results of computer evaluation show that in most practical cases, i.e. when the interference has a correlation coefficient greater than 0.8, the performance of the suboptimal method of linear prediction is very close to the optimum one. Moreover, the linear prediction method gives a greater flatness in frequency response and, as far as implementation is concerned, is much simpler.
E-Plane Forked Hybrid-T Junction

A novel rearrangement of the waveguides of a microwave hybrid-T junction has been investigated. This junction is formed by the intersection of four rectangular waveguides, two of which (conventionally E and H arms) are mutually perpendicular, cross-polarized, and have their centerlines in one symmetry plane of the junction; the remaining two waveguide arms are formed by symmetric E-plane bifurcation of the E-arm waveguide extended. This hybrid T possesses special advantages with regard to match and pulse power capacity. A special test fixture was constructed of 1.122- X 0.497-inch rectangular waveguide. Experimental design work was carried out over a 12 per cent range of frequencies from 8.5 to 9.6 kmc. The H-arm reflection was reduced to 2.6-db standing-wave ratio (swr) by simple shaping of the bifurcating element. Addition of conventional matching elements resulted in maximum reflections, within the above band, of 0.8 and 0.6 db swr in the H and E arms, respectively. The ultimate limitation on the E-arm power capacity, as fixed by the intensified electric field at the leading (rounded) edge of the center partition, was computed to be 2 db below uniform waveguide. Experimental corroboration has been obtained.
Influence of magnetic reluctances of magnetic elements on servo valve torque motors

The current research of electro-hydraulic servo valves mainly focuses on the vibration, pressure oscillating and source of noise. Unfortunately, literatures relating to the study of the influence of the magnetic reluctances of the magnetic elements are rarely available. This paper aims to analyze the influence of the magnetic reluctances of the magnetic elements on torque motor. Considering these magnetic reluctances ignored in previous literatures, a new mathematical model of servo valve torque motor is developed and proposed based on the fundamental laws of electromagnetism. By using this new mathematical model and the previous models, electromagnetic torque constant and magnetic spring stiffness are evaluated for a given set of torque motor parameters. A computer simulation by using AMESim software is also performed for the same set of torque motor parameters to verify the proposed model. The theoretical results of electromagnetic torque constant and magnetic spring stiffness evaluated by the proposed model render closer agreement with the simulation results than those evaluated by the previous models. In addition, an experimental measurement of the magnetic flux densities in the air-gaps is carried out by using SFL218 servo valve torque motor. Compared with the theoretical results of the magnetic flux densities in the air-gaps evaluated by the previous models, the theoretical results evaluated by the proposed model also show better agreement with the experimental data. The proposed model shows the influence of the magnetic reluctances of the magnetic elements on the servo valve torque motor, and offers modified and analytical expressions to electromagnetic torque constant and magnetic spring stiffness. These modified and analytical expressions could provide guidance more accurately for a linear control design approach and sensitivity analysis on electro-hydraulic servo valves than the previous expressions.
Effector genes in Magnaporthe oryzae Triticum as Potential Targets for Incorporating Blast Resistance in Wheat.

Wheat blast (WB), caused by Magnaporthe oryzae Triticum pathotype, recently emerged as a destructive disease that threatens global wheat production. Since few sources of genetic resistance have been identified in wheat, genetic transformation of wheat with rice blast resistance genes could expand resistance to WB. We evaluated the presence/absence of homologs of rice blast effector genes in Triticum isolates with the aim of identifying avirulence genes in field populations whose cognate rice resistance genes could potentially confer resistance to WB. We also assessed presence of the wheat pathogen AVR-Rmg8 gene, and identified new alleles. A total of 102 isolates collected in Brazil, Bolivia and Paraguay from 1986 to 2018 were evaluated by PCR using 21 pairs of gene-specific primers. Effector gene composition was highly variable, with homologs to AvrPiz-t, AVR-Pi9, AVR-Pi54 and ACE1 showing the highest amplification frequencies (>94%). We identified Triticum isolates with a functional AvrPiz-t homolog that triggers Piz-t-mediated resistance in the rice pathosystem, and produced transgenic wheat plants expressing the rice Piz-t gene. Seedlings and heads of the transgenic lines were challenged with isolate T25 carrying functional AvrPiz-t. Although slight decreases in the percentage of diseased spikelets and leaf area infected were observed in two transgenic lines, our results indicated that Piz-t did not confer useful WB resistance. Monitoring of avirulence genes in populations is fundamental to identifying effective resistance genes for incorporation into wheat by conventional breeding or transgenesis. Based on avirulence gene distributions, rice resistance genes Pi9 and Pi54 might be candidates for future studies.
A Generalized Formulation for the Contact Between Elastic Spheres: Applicability to Both Wet and Dry Conditions

The interaction between two elastic spheres with an intervening liquid film of given volume is studied theoretically. Using an energy minimization approach, equilibrium contact configurations are determined through numerical computation. Several dimensionless groups are identified that govern the character of the solution. Curve fits are performed to reveal analytical relationships among the dimensionless groups. At extreme values of particular parameters, the curve fits are found to recover the analytical results of the well-known Hertzian and Johnson-Kendall-Roberts elastic (dry contact) models, as well as the force of a liquid bridge between rigid spheres. Qualitative agreement is found between the current model and some published experiments.
HeartNet: Self Multihead Attention Mechanism via Convolutional Network With Adversarial Data Synthesis for ECG-Based Arrhythmia Classification

Cardiovascular disease is now one of the leading causes of morbidity and mortality. Electrocardiogram (ECG) is a reliable tool for monitoring the health of the cardiovascular system. Currently, there has been a lot of focus on accurately categorizing heartbeats. There is a high demand for automatic ECG classification systems to assist medical professionals. But there is a big issue in obtaining original data extensively in medical domains in rare diseases, so it is essential to have a robust solution adopting this challenge. So, we need a solution that can address the problem of tackling data insufficiency, which is a major concern nowadays for medical applications. Without having, significant training samples the overall output can be demised. But the recent works on ECG classification did not address the challenge of solving the data insufficiency label problem. To overcome this issue, we developed a new generative adversarial network-based deep learning method called HeartNet for tackling the data insufficiency problem. The proposed deep learning method is compressed by a multi-head attention mechanism on CNN architecture. The main challenge of insufficient data labels is solved by adversarial data synthesis by adopting a generative adversarial network (GAN) with generating additional training samples. It drastically improves the overall performance of the proposed method by 5-10% on each insufficient data label category. Since the training samples are increased. We evaluated our proposed method utilizing the MIT-BIH dataset. Our proposed method has shown $99.67\pm {0.11}$ accuracy and 89.24± 1.71 MCC trained with adversarial data synthesized dataset. However, we have also utilized two individual datasets as Atrial Fibrillation Detection Database and PTB Diagnostic Database to see the performance and generalization of our proposed model on ECG classification. The effectiveness and robustness of the proposed method are validated by extensive experiments, comparison, and analysis. Later on, we also highlighted some limitations of this work.
A nationwide deep learning pipeline to predict stroke and COVID-19 death in atrial fibrillation

Deep learning (DL) and machine learning (ML) models trained on long-term patient trajectories held as medical codes in electronic health records (EHR) have the potential to improve disease prediction. Anticoagulant prescribing decisions in atrial fibrillation (AF) offer a use case where the benchmark stroke risk prediction tool (CHA2DS2-VASc) could be meaningfully improved by including more information from a patient's medical history. In this study, we design and build the first DL and ML pipeline that uses the routinely updated, linked EHR data for 56 million people in England accessed via NHS Digital to predict first ischaemic stroke in people with AF, and as a secondary outcome, COVID-19 death. Our pipeline improves first stroke prediction in AF by 17% compared to CHA2DS2-VASc (0.61 (0.57-0.65) vs 0.52 (0.52-0.52) area under the receiver operating characteristics curves, 95% confidence interval) and provides a generalisable, opensource framework that other researchers and developers can build on.
The lose-to-win strategy of the weak: intraspecific parasitism via egg abduction in a termite

Predation by larger conspecifics poses a major threat to small juveniles in many animal species. However, in social insects, raids perpetrated by large colonies may provide smaller colonies with opportunities for parasitization. Herein, in the termite Reticulitermes speratus, we demonstrate that small incipient colonies parasitize large mature colonies through egg abduction when attacked by raiding conspecifics. We observed that the eggs of incipient colonies were brought into raiding colonies while their parents were killed during the attack. In this species, unmated females found new colonies with female–female (FF) cooperation, in addition to the typical monogamous colony foundation. Interestingly, the abducted eggs of FF pairs developed into nymphs (reproductive caste) in the raiding colonies, whereas the eggs of male–female (MF) pairs developed into workers (non-reproductive caste). Parthenogenetic eggs are known to be developmentally predisposed to becoming female reproductives owing to genomic imprinting in termites. This study demonstrates that the plundering of small colonies by larger conspecific colonies not only results in the extinction of the weaker colonies, but also serves as a strategy that incipient colonies use to obtain the reproductive position in large colonies by stealth. The results elucidate the diversity and complexity of inter-colonial interactions in social insects.
Friction characteristics of the curved sidewall surfaces of a rotary MEMS device in oscillating motion

A MEMS device with a configuration similar to that of a micro-bearing was developed to study the friction behavior of the curved sidewall surfaces. This friction-testing device consists of two sets of actuators for normal motion and rotation, respectively. Friction measurements were performed at the curved sidewall surfaces of single-crystal silicon. Two general models were developed to determine the equivalent tangential stiffness of the bush-flexure assembly at the contact point by reducing a matrix equation to a one-dimensional formulation. With this simplification, the motions of the contacting surfaces were analyzed by using a recently developed quasi-static stick-slip model. The measurement results show that the coefficient of static friction exhibits a nonlinear dependence on the normal load. The true coefficient of static friction was determined by fitting the experimental friction curve.
Identification and Functional Verification Reveals that miR-195 Inhibiting THRSP to Affect Fat Deposition in Xinyang Buffalo

The buffalo population is extensive in China, but its meat quality is relatively inferior. Therefore, improving meat quality should be one of the breeding goals. microRNAs (miRNAs) play an essential regulatory role in the post-transcriptional expression of genes. Some studies have reported their function regulating genes related to fat deposition and adipocyte differentiation in cattle, but there is limited reports in buffalo. We performed small RNA transcriptome sequencing of Xinyang buffalo adipose tissue between calves and adults in this study. As a result, 282 mature miRNAs were significantly differentially expressed, and co-expression analysis showed that 454 miRNAs were significantly associated with developmental stages. Target gene identification, GO (gene ontology) annotation, and KEGG analysis of miRNAs showed that miR-195, miR-192, and miR-24-3p could target key genes for lipogenesis and thus regulate adipose deposition and differentiation. Among them, miR-195 was significantly upregulated in adipose tissue and induced adipocytes of adult buffaloes, and its overexpression significantly inhibited lipid accumulation in primary adipocytes. Dual-luciferase reporter gene analysis showed that miR-195 reduced the expression of thyroid hormone response protein (THRSP) by targeting its 3′ untranslated terminal region, suggesting that miR-195 may inhibit lipid accumulation in adipocytes by regulating THRSP. The results confirmed the reliability of predictive screening of miRNAs and provided theoretical support for buffalo fattening.
Recent Development of Probiotic Bifidobacteria for Treating Human Diseases

Bifidobacterium is a non-spore-forming, Gram-positive, anaerobic probiotic actinobacterium and commonly found in the gut of infants and the uterine region of pregnant mothers. Like all probiotics, Bifidobacteria confer health benefits on the host when administered in adequate amounts, showing multifaceted probiotic effects. Examples include B. bifidum, B. breve, and B. longum, common Bifidobacterium strains employed to prevent and treat gastrointestinal disorders, including intestinal infections and cancers. Herein, we review the latest development in probiotic Bifidobacteria research, including studies on the therapeutic impact of Bifidobacterial species on human health and recent efforts in engineering Bifidobacterium. This review article would provide readers with a wholesome understanding of Bifidobacteria and its potentials to improve human health.
Assessment of Stability of MIMU Probes to Skin-Marker-Based Anatomical Reference Frames During Locomotion Tasks: Effect of Different Locations on the Lower Limb

Soft tissue artefacts (STAs) undermine the validity of skin-mounted approaches to measure skeletal kinematics. Magneto-inertial measurement units (MIMU) gained popularity due to their low cost and ease of use. Although the reliability of different protocols for marker-based joint kinematics estimation has been widely reported, there are still no indications on where to place MIMU to minimize STA. This study aims to find the most stable positions for MIMU placement, among four positions on the thigh, four on the shank, and three on the foot. Stability was investigated by measuring MIMU movements against an anatomical reference frame, defined according to a standard marker-based approach. To this aim, markers were attached both on the case of each MIMU (technical frame) and on bony landmarks (anatomical frame). For each MIMU, the nine angles between each versor of the technical frame with each versor of the corresponding anatomical frame were computed. The maximum standard deviation of these angles was assumed as the instability index of MIMU-body coupling. Six healthy subjects were asked to perform barefoot gait, step negotiation, and sit-to-stand. Results showed that (1) in the thigh, the frontal position was the most stable in all tasks, especially in gait; (2) in the shank, the proximal position is the least stable, (3) lateral or medial calcaneus and foot dorsum positions showed equivalent stability performances. Further studies should be done before generalizing these conclusions to different motor tasks and MIMU-body fixation methods. The above results are of interest for both MIMU-based gait analysis and rehabilitation approaches using wearable sensors-based biofeedback.
Design of a switched reluctance machine for extended speed operation

This paper presents results from a design study investigating the feasibility of high efficiency, switched reluctance (SR) machines for application in minimal hybrid electric vehicles. The application requirements are presented, highlighting the constraining influences of the vehicle drive-line topology on the machine design. The benefit of continuous phase current excitation is reported for the first time, illustrating that constant power at extended speed operation can be realised with a higher number of phase winding turns per pole than would otherwise be achieved with conventional discontinuous current control. Thus, the torque/Ampere at, and below, base-speed is not as significantly compromised, an important consideration for the power inverter silicon rating and hence drive system cost. Validation of the design procedure and simulated results is presented via the correlation of simulated and test data taken from a prototype machine. The results demonstrate the potential of the SR technology for high performance, low cost automotive applications, combining arduous environmental and volumetric constraints.