Miracle-dz/UniFAR-FTUs huggingface dataset:
Modelling of Hepatitis E virus RNA-dependent RNA polymerase genotype 3 from a chronic patient and in silico interaction analysis by molecular docking with Ribavirin

Abstract Hepatitis E Virus (HEV) infection is an emergent zoonotic disease, where chronic hepatitis E associated to solid organ transplant (SOT) recipients, related to genotype 3, is the clinical manifestation of major concern. In this setting, ribavirin (RBV) treatment is the only available therapy, though drug-resistant variants could emerge leading to a therapeutic failure. Crystallographic structures have not been reported for most of the HEV proteins, including the RNA-polymerase (RdRp). Therefore, the mechanism of action of RBV against HEV and the molecular interactions between this drug and RdRp are largely unknown. In this work, we aimed to model in silico the 3 D structure of a novel HEV3 RdRp (HEV_C1_Uy) from a chronically HEV infected-SOT recipient treated with RBV and to perform a molecular docking simulation between RBV triphosphate (RBVT), 7-methyl-guanosine-5'-triphosphate and the modelled protein. The models were generated using I-TASSER server and validated with multiple bioinformatics tools. The docking analysis were carried out with AutoDock Vina and LeDock software. We obtained a suitable model for HEV_C1_Uy (C-Score=-1.33, RMSD = 10.4 ± 4.6 Å). RBVT displayed a binding affinity of −7.6 ± 0.2 Kcal/mol by molecular docking, mediated by 6 hydrogen-bonds (Q195-O14, S198-O11, E257-O13, S260-O2, O3, S311-O11) between the finger’s-palm-domains and a free binding energy of 31.26 ± 16.81 kcal/mol by molecular dynamics simulations. We identified the possible HEV RdRp interacting region for incoming nucleotides or analogs and provide novel insights that will contribute to better understand the molecular interactions of RBV and the enzyme and the mechanism of action of this antiviral drug. Communicated by Ramaswamy H. Sarma.
Thinning Technology of Patterned Silicon Wafer for Micro Pressure Sensor

Recently, the research of the gene using the transgenic mouse has been performed for the development of new medicines. However, 600,000 kinds of mice are produced for the elucidation of each gene function. For this reason, the intelligent microchips have been developed to obtain an individual identification and biological information. The ventricular rate of a mouse can be monitored by the micro pressure sensor mounted on the intelligent microchip. In this research, the detailed structure and functions of the micro pressure sensor were investigated by the FEM analysis, and the sensor-chips were manufactured on 6-inch silicon wafer. The wafer thickness had to be reduced owing to the size restriction of the intelligent microchip. The grinding of the 6-inch silicon wafer with 560 µm in thickness with 19200 sensor-chips was carried out by the newly developed thinning technology. After the basic characteristics of a sensor-chip were evaluated, the output profile containing small peaks corresponding to the heartbeat of a transgenic mouse was finally detected using a mounted sensor-chip.
The Suboptimal Pediatric HIV Viral Load Cascade

Background: Children living with HIV and taking antiretroviral therapy (ART) are a priority group for routine viral load (VL) monitoring. As per Lesotho guidelines, a VL ≥1000 copies/mL (“unsuppressed”) should trigger adherence counseling and a follow-up VL; 2 consecutive unsuppressed VLs (“virologic failure”) qualify for switching to second-line ART, with some exceptions. Here, we describe the pediatric VL cascade in Lesotho. Methods: In a prospective open cohort study comprising routine VL results from 22 clinics in Lesotho, we assessed outcomes along the VL cascade for children who had at least 1 VL test from January 2016 through June 2020. Data were censored on February 10, 2021. Results: In total, 1215 children received 5443 VL tests. The median age was 10 years (interquartile range 7–13) and 627/1215 (52%) were female; 362/1215 (30%) had at least 1 unsuppressed VL. A follow-up VL was available for 325/362 (90%), although only for 159/362 (44%) within 6 months of the first unsuppressed VL. Of those with a follow-up VL, 172/329 (53%) had virologic failure and 123/329 (37%) qualified for switching to second-line ART. Of these, 55/123 (45%) were ever switched, although only 9/123 (7%) were switched within 12 weeks of the follow-up VL. Delays were more pronounced in rural facilities. Overall, 100/362 (28%) children with an unsuppressed VL received a timely follow-up VL and, if required, a timely regimen switch. Conclusions: Despite access to VL monitoring, clinical management was suboptimal. HIV programs should prioritize timely clinical action to maximize the benefits of VL monitoring.
An ultra‐wideband bandpass filter using hybrid structure of microstrip and CPW

An ultra‐wideband (UWB) bandpass filter is proposed based on the hybrid structure of microstrip and coplanar waveguide (CPW). First, the detached‐mode resonator is formed on the CPW layer, which composes a quarter‐wavelength (λ/4) multiple‐mode resonator (MMR) with a short‐stub and a λ/4 single‐mode resonator. Then, two λ/4 microstrip open‐stubs on the top side of the common substrate are introduced for bandwidth enhancement to meet the UWB passband limit. Quasi‐elliptic function response and UWB operation are achieved. The simulated and measured results show an excellent agreement. © 2009 Wiley Periodicals, Inc. Microwave Opt Technol Lett 51: 2470–2473, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.24658
Digital Discovery: A Model for Integrating Digital Interactives During Social Studies Lessons

The Internet offers a wide array of resources for social studies teachers. Digital interactives, in particular, offer promise. They combine images, sounds, videos, and animation and are organized around specific themes or historical subjects. Verizon’s Thinkfinity and the Public Broadcasting Service’s Learning Media websites are two leading collections of this style of resource. With an efficient search and thoughtful planning, teachers can use digital interactives to create more engaging and exciting learning experiences for their students. This article proposes a four-step model that can be used to assist teachers in finding these resources and integrating them into social studies lessons. The model invites teachers to determine curricular needs, search the digital landscape, establish entry points, then build the digital interactive-enhanced lesson.
On the effect of MOX fuel conductivity in predicting melting in FR fresh fuel by means of TRANSURANUS code

The capability of the fuel to operate at high power without melting is important to Fast Reactors. Reactor design limits normally require that there be a low probability of fuel melting during steady-state operation, including overpower conditions. This requirement has a direct effect on the steady-state power limit of the fuel pin and hence on the reactor power. The development of computational tools that are able to capture the occurrence of high temperature phenomena and mechanisms is thus an important step in reducing the margin of conservatisms and increasing the reactor efficiency. Among the experiments that were conducted for this purpose, HEDL P-19 experiment has been selected and simulated using TRANSURANUS code to exploit its capability to capture the inception of MOX fuel melting. The experiment included 8 fresh pins with cladding Outside Diameters (OD) 5.84 mm, and 8 fresh 6.35 mm OD pins. It was performed during 1971 to investigate the effect of the initial fuel-to-cladding diametric gap size (from 0.086 to 0.25 mm) on the linear heat rate needed to initiate incipient melting at beginning-of-life. All 5.84 mm OD pins with fuel-to-cladding gaps equal to or less than 0.14 mm had no fuel melting. The remaining 5.84 mm OD pins and all the 6.35 mm OD pins experienced partial fuel melting. This work reported hereafter consists of two parts. The main objective of the first one is to assess the capability of TRANSURANUS to predict the measured melting heights of the tested rods and its implications on the thermal conductivity correlations implemented in the code. The second part included modifications that targeted the high temperature thermal conductivity term in two TRANSURANUS correlations. The modifications were incorporated into the code that was recompiled.
The significant factors causing delay of building construction projects in Malaysia

Purpose – The paper seeks to identify the major factors causing delay in building construction projects in Malaysia.Design/methodology/approach – A questionnaire survey was used to carry out the study. The questionnaire consisted of 31 factors which were grouped into four major categories by responsibility – contractor factors, owner factors, consultant factors and external factors. The level of importance of the categories was measured and the relative importance of weights was ranked.Findings – The study finds that financial problems are the main factor and coordination problems are the second most important factor causing delay in construction projects in Malaysia. The results were analyzed to rank the causes of delay and further classify the types of delay.Research limitations/implications – The scope of this study is limited to building projects in the Klang Valley area, where major Malaysian cities such as Kuala Lumpur, Putrajaya, Petaling Jaya, Shah Alam and Seremban are located. The data for this .
Experience-Dependent Modulation of Rubber Hand Illusion in Badminton Players.

Badminton players have a plastic modification of their arm representation in the brain due to the prolonged use of their racket. However, it is not known whether their arm representation can be altered through short-term visuotactile integration. The neural representation of the body is easily altered when multiple sensory signals are integrated in the brain. One of the most popular experimental paradigms for investigating this phenomenon is the "rubber hand illusion. " This study was designed to investigate the effect of prolonged use of a racket on the modulation of arm representation during the rubber hand illusion in badminton players. When badminton players hold the racket, their badminton experience in years is negatively correlated with the magnitude of the rubber hand illusion. This finding suggests that tool embodiment obtained by the prolonged use of the badminton racket is less likely to be disturbed when holding the racket.
Rho kinase inhibition ameliorates vascular remodeling and blood pressure elevations in a rat model of apatinib-induced hypertension

Objectives: Hypertension is one of the major adverse effects of tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factors. However, the mechanism underlying TKIs-induced hypertension remains unclear. Here, we explored the role of the RhoA/Rho kinase (ROCK) signaling pathway in elevation of blood pressure (BP) induced by apatinib, a selective TKI approved in China for treatment of advanced or metastatic gastric cancer. A nonspecific ROCK inhibitor, Y27632, was then combined with apatinib and its efficacy in alleviating apatinib-induced hypertension was evaluated. Methods: Normotensive female Wistar–Kyoto rats were exposed to two different doses of apatinib, or apatinib combined with Y27632, or vehicle for 2 weeks. BP was monitored by a tail-cuff plethysmography system. The mRNA levels and protein expression in the RhoA/ROCK pathway were determined, and vascular remodeling assessed. Results: Administration of either a high or low dose of apatinib was associated with a rapid rise in BP, reaching a plateau after 12 days. Apatinib treatment mediated upregulation of RhoA and ROCK II in the mid-aorta, more significant in the high-dose group. However, ROCK I expression showed no statistically significant differences. Furthermore, the mRNA level of GRAF3 decreased dose-dependently. Apatinib administration was also associated with decreased levels of MLCP, and elevated endothelin-1 (ET-1) and collagen I, which were accompanied with increased mid-aortic media. However, treatment with Y27632 attenuated the above changes. Conclusion: These findings suggest that activation of the RhoA/ROCK signaling pathway could be the underlying mechanism of apatinib-induced hypertension, while ROCK inhibitor have potential therapeutic value.
AMSTE precision fire control tracking overview

The DARPA Affordable Moving Surface Target Engagement (AMSTE) program is a research effort to develop a system concept to track and engage a moving surface target with a single unitary warhead. Engaging a moving surface target requires precision tracking to a degree that has not been demonstrated in previous work. Tracking moving surface targets is especially difficult because of the targets ability to maneuver in unpredictable ways, such as coming to a stop, and the potential for a large number of nearby confusing targets. Because of the importance of tracking to the overall AMSTE system, a significant portion of the program is dedicated to developing advanced tracking algorithms. This paper will briefly describe the current state of the art of surface target trackers developed under the DARPA Moving Target Exploitation (MTE) program. It then identifies the inadequacies in association and bias removal that must be overcome to obtain the high fidelity tracks required for weapon targeting. The improved tracking techniques discussed include the use of data from multiple Ground Moving Target Indicator (GMTI) sensors to improve location accuracy, bias removal techniques, advanced multiple hypothesis trackers, variable state interacting multiple models using higher order motion models, feature aided tracking and terrain analysis.
Is SARS‐CoV‐2 viral clearance in nasopharyngeal swabs an appropriate surrogate marker for clinical efficacy of neutralising antibody‐based therapeutics?

Viral clearance is likely the best way to assess the efficacy of antibody‐based therapies. Although antibodies can mediate a variety of effects that include modulation of inflammation, the demonstration of viral clearance provides an accessible and measurable parameter that can be used to evaluate efficacy and determine dosing. Therefore, it is important to ascertain the ability of monoclonal antibodies and convalescent plasma to effect viral clearance. For COVID‐19, which is caused by the respiratory virus SARS‐CoV‐2, the most common assay to assess viral clearance is via a nasopharyngeal swab (NPS). However, assessment of antibody efficacy by sampling this site may be misleading because it may not be as accessible to serum antibodies as respiratory secretions or circulating blood. Adding to the complexity of assessing the efficacy of administered antibody, particularly in randomised controlled trials (RCTs) that enroled patients at different times after the onset of COVID‐19 symptoms, viral clearance may also be mediated by endogenous antibody. In this article we critically review available data on viral clearance in RCTs, matched control studies, case series and case reports of antibody therapies in an attempt to identify variables that contribute to antibody efficacy and suggest optimal strategies for future studies.
Factor Structure and Criterion-Related Validity of the Air Force Officer Qualifying Test Form T for Pilot Applicants

The Air Force Officer Qualifying Test (AFOQT) is the primary selection tool for officer applicants in the U.S. Air Force (USAF) for nearly seven decades. The AFOQT is revised and modified periodically, with rigorous equating and linking effort to ensure comparability and connectivity across forms. The most recent version of AFOQT is Form T that includes 10 cognitive ability and knowledge subtests. Despite the continuing validation effort of the AFOQT across forms, it was mostly directed to the general population of officer applicants, but not to any specific subpopulation. The current investigation reported three studies in an attempt to provide evidence for factor structure and criterion-related validity of AFOQT Form T for pilot applicants via four analytical approaches: meta-analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and structural equation modeling (SEM). The results suggested that AFOQT Form T data are best represented by a bifactor model with a general ability and four specific abilities, and that each latent construct has a distinct predictive utility for pilot performance criteria.
Exploring key stakeholders’ attitudes and opinions on medical assistance in dying and palliative care in Canada: a qualitative study protocol

Introduction Canadians have had legal access to medical assistance in dying (MAiD) since 2016. However, despite substantial overlap in populations who request MAiD and who require palliative care (PC) services, policies and recommended practices regarding the optimal relationship between MAiD and PC services are not well developed. Multiple models are possible, including autonomous delivery of these services and formal or informal coordination, collaboration or integration. However, it is not clear which of these approaches are most appropriate, feasible or acceptable in different Canadian health settings in the context of the COVID-19 pandemic and in the post-pandemic period. The aim of this qualitative study is to understand the attitudes and opinions of key stakeholders from the government, health system, patient groups and academia in Canada regarding the optimal relationship between MAiD and PC services. Methods and analysis A qualitative, purposeful sampling approach will elicit stakeholder feedback of 25–30 participants using semistructured interviews. Stakeholders with expertise and engagement in MAiD or PC who hold leadership positions in their respective organisations across Canada will be invited to provide their perspectives on the relationship between MAiD and PC; capacity-building needs; policy development opportunities; and the impact of the COVID-19 pandemic on the relationship between MAiD and PC services. Transcripts will be analysed using content analysis. A framework for integrated health services will be used to assess the impact of integrating services on multiple levels. Ethics and dissemination This study has received ethical approval from the University Health Network Research Ethics Board (No 19-5518; Toronto, Canada). All participants will be required to provide informed electronic consent before a qualitative interview is scheduled, and to provide verbal consent prior to the start of the qualitative interview. Findings from this study could inform healthcare policy, the delivery of MAiD and PC, and enhance the understanding of the multilevel factors relevant for the delivery of these services. Findings will be disseminated in conferences and peer-reviewed publications.
Leveraging node heterogeneity to improve content discovery and content retrieval in peer-to-peer networks

Distributed content-addressed networks like the Interplanetary File System (IPFS) have gained popularity in recent years. It is used as a data storage layer for Blockchain applications or generally as a censorship-resistant file-sharing network. In the past, many traditional peer-to-peer networks eventually implemented super-peer sub-topologies within their otherwise nonhierarchical network to increase the efficiency of various system tasks. While it can be observed that IPFS also holds such tendencies, no formalism supports these developments. This article will present a research project that will investigate if and how a super-peer architecture can complement the IPFS network from a content discovery and retrieval perspective. Further, first preliminary results on peer churn rate in the IPFS and Filecoin networks will be discussed.
Proliferative, contractile, and biosynthetic activity of adult canine articular chondrocytes in Type I and II collagen-glycosaminoglycan matrices in vitro

One tissue engineering approach being investigated for the treatment of defects in articular cartilage involves the implantation of autologous chondrocyte-seeded absorbable scaffolds. The purpose of this thesis was to establish a foundation for future studies by investigating the behavior of freshly isolated and passaged chondrocytes in scaffolds of different composition. This study evaluated the effects of passage number (freshly isolated and passages 1 and 2) and collagen type on the proliferation, contraction, and biosynthetic activity of adult canine articular chondrocytes grown in type I and II collagen-glycosaminoglycan matrices. Adult articular chondrocytes were acquired from 8 canines, and either freshly isolated cells or cells cultured in monolayer up to two passages were seeded into porous type I and type II collagen-glycosaminoglycan matrices (CG). These porous scaffolds were manufactured by freeze-drying and were subsequently cross-linked by dehydrothermal (DHT) and carbodiimide (EDAC) treatments. The matrices were cut to disks 4mm in diameter by 3mm thick and were dynamically seeded at a cell density of 10,000 chondrocytes/mm 3. The type II CG matrices were terminated at 1-day and 1, 2, 4, 8, and 12 weeks in culture. Culture of the type I matrices was terminated after 1-day and 1 and 4 weeks. EDAC cross-linking imparted a degree of mechanical stiffness to the matrices such that they adequately resisted the smooth muscle actin-enabled contraction. PO, P1, and P2 cells seeded in the type II matrices continued to proliferate over a 4-week period, but thereafter the PO and P1 cells continued to increase in number and the P2 cells decreased. It was demonstrated that collagen type (type I or type II) did not have a significant effect on DNA content, GAG content, or biosynthesis for up to 4 weeks when all data were included. Due to the variance in data, statistical outliers were excluded and statistical analyses revealed a significant effect of collagen type on protein and GAG synthesis with higher levels in the type II scaffold. Western blot analysis demonstrated that P1 and P2 cells seeded in the type II matrices were capable of synthesizing type II collagen thus demonstrating that they retained the articular chondrocyte phenotype. These findings support the continued investigation of type I or II CG matrices seeded with second passage chondrocytes and culture for 4 weeks as implants for articular cartilage tissue engineering. The advantage of being able to culture chondrocytes for 2 passages is that greater numbers of cells can be made available for seeding purposes. Thesis Supervisor: Myron Spector Title: Senior Lecturer, Department of Mechanical Engineering Professor of Orthopaedic Surgery (Biomaterials), Harvard Medical School
Design criteria for laboratory measurements of low permeability rocks

The advantages and limitations of two versions of the pulse technique for laboratory measurements of low permeabilities (10−16 to 10−24 m²) are discussed. The transient pulse technique developed by Brace et al. [1968] is the preferred method because of the ease of data reduction. The modified transient pulse technique developed by Trimmer et al. [1980] can be used when the assumptions inherent in the transient pulse technique are invalid. The systematic error associated with the transient pulse technique is a function of the ratio of the effective sample pore volume to the reservoir volumes. If this ratio is less than 0.25, then the error associated with the transient technique is less than 10%. The modified transient pulse technique does not suffer from this systematic error. Criteria are also presented for optimizing the experimental configuration for measurement durations as well as ease of data reduction.