Miracle-dz/UniFAR-FTUs huggingface dataset:
Gain-of-Sensitivity Mutations in a Trim 5-Resistant Primary Isolate of Pathogenic SIV Identify Two Independent Conserved Determinants

Retroviral capsid recognition by Trim5 blocks productive infection. Rhesus macaques harbor three functionally distinct Trim5 alleles: Trim5a, Trim5a and Trim5. Despite the high degree of amino acid identity between Trim5a and Trim5a alleles, the Q/TFP polymorphism results in the differential restriction of some primate lentiviruses, suggesting these alleles differ in how they engage these capsids. Simian immunodeficiency virus of rhesus macaques (SIVmac) evolved to resist all three alleles. Thus, SIVmac provides a unique opportunity to study a virus in the context of the Trim5 repertoire that drove its evolution in vivo. We exploited the evolved rhesus Trim5a resistance of this capsid to identify gain-ofsensitivity mutations that distinguish targets between the Trim5a and Trim5a alleles. While both alleles recognize the capsid surface, Trim5a and Trim5a alleles differed in their ability to restrict a panel of capsid chimeras and single amino acid substitutions. When mapped onto the structure of the SIVmac239 capsid N-terminal domain, single amino acid substitutions affecting both alleles mapped to the b-hairpin. Given that none of the substitutions affected Trim5a alone, and the fact that the b-hairpin is conserved among retroviral capsids, we propose that the b-hairpin is a molecular pattern widely exploited by Trim5a proteins. Mutations specifically affecting rhesus Trim5a (without affecting Trim5a) surround a site of conservation unique to primate lentiviruses, overlapping the CPSF6 binding site. We believe targeting this site is an evolutionary innovation driven specifically by the emergence of primate lentiviruses in Africa during the last 12 million years. This modularity in targeting may be a general feature of Trim5 evolution, permitting different regions of the PRYSPRY domain to evolve independent interactions with capsid. Citation: McCarthy KR, Schmidt AG, Kirmaier A, Wyand AL, Newman RM, et al. (2013) Gain-of-Sensitivity Mutations in a Trim5-Resistant Primary Isolate of Pathogenic SIV Identify Two Independent Conserved Determinants of Trim5a Specificity. PLoS Pathog 9(5): e1003352. doi:10.1371/journal.ppat. 1003352 Editor: Michael Emerman, Fred Hutchinson Cancer Research Center, United States of America Received November 25, 2012; Accepted March 25, 2013; Published May 9, 2013 Copyright: 2013 McCarthy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by NIH grants AI095092 and AI083118 to WEJ (http://www.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: welkin.johnson@bc.edu
Electrospun homogeneous silk fibroin/poly (ɛ-caprolactone) nanofibrous scaffolds by addition of acetic acid for tissue engineering

In this study, we investigated the phase separation phenomenon of silk fibroin/poly (ɛ-caprolactone) electrospinning solution to improve the performance of silk fibroin/poly (ɛ-caprolactone) electrospun nanofibers. It showed that phase separation does occur in just a few hours in the silk fibroin/poly (ɛ-caprolactone)/formic acid mixture solution. Acetic acid, small molecule nonsolvent for silk fibroin, was first introduced to silk fibroin/poly (ɛ-caprolactone)/formic acid solution, a homogeneous solution without separation for over several days was achieved after mixing for 5 h. The morphology and composition of the silk fibroin/poly (ɛ-caprolactone) and acetic acid-modified silk fibroin/poly (ɛ-caprolactone) fibrous scaffolds were examined by scanning electron microscopy, Fourier transform infrared spectroscopy and thermal gravimetric analyzer. Attachment and proliferation of mouse osteoblast MC3T3-E1 cells were tested by scanning electron microscopy and cytotoxity assay. The results indicated that the phase separation of silk fibroin/poly (ɛ-caprolactone) solution might led to inhomogeneous morphology and composition of the composite scaffolds, and the inhomogeneity of the silk fibroin/poly (ɛ-caprolactone) scaffolds with formic acid as solvent had a remarkable difference on cell adhesion and proliferation. In contrast, there was no significant difference among the silk fibroin/poly (ɛ-caprolactone) scaffolds with formic acid/acetic acid as solvent because of their good consistency in fiber morphology and composition. These obtained silk fibroin/poly (ɛ-caprolactone) nanofibers had small average diameter of 190 ± 40 nm. The obtained results proved that this study provided a facile and effective approach to achieve compositionally homogeneous silk fibroin/poly (ɛ-caprolactone) scaffolds with formic acid as solvent for effective applications.
Polymer thermal and acoustic properties using heterodyne detected transient grating technique

We investigated the acoustic and thermal features of a polymeric system by a heterodyne detected transient grating technique. We studied two polymers characterized by different molecular weights. Transient grating experiments could reveal a reliable series of information on sound velocity, acoustic damp- ing time, and thermal diffusion of the polymers. The tempera- ture and molecular weight dependence of the polymer acoustic and thermal properties are reported. V C 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 49: 685-690, 2011
Association between district-level perceived safety and self-rated health: a multilevel study in Seoul, South Korea

Objectives Several studies have reported the relationship between residents’ perceived neighbourhood safety and their health outcomes. However, those studies suffered from unreliability of neighbourhood safety measure and potential residual confounding related to crime rates. In this study, using multilevel analysis to account for the hierarchical structure of the data, we examined associations between district-level perceived safety and self-rated health after adjusting for potential confounders including the district-level crime rate. Design Cross-sectional study. Setting We used the first wave of Seoul Welfare Panel Study, which has 7761 individuals from 3665 households in 25 administrative districts in Seoul, South Korea. District-level perceived safety was obtained by aggregating responses from the residents that are representative samples for each administrative district in Seoul. To examine an association between district-level safety and residents’ self-rated health, we used mixed effect logistic regression. Results Our results showed that higher district-level perceived safety, an aggregated measure of district residents’ responses towards neighbourhood safety, was significantly associated with poor self-rated health after controlling for sex, age, education level, job status, marital status and household income (OR=0.87, 95% CI 0.78 to 0.97). Furthermore, this association was still robust when we additionally adjusted for the district-level crime rate (OR=0.86, 95% CI 0.77 to 0.95). Conclusions Our study highlights the importance of improving neighbourhood perceived safety to enhance residents’ health.
An Analytical Quantum Model to Calculate Fluorescence Enhancement of a Molecule in Vicinity of a Sub-10 nm Metal Nanoparticle

An analytical quantum model is used to calculate electrical permittivity of a metal nanoparticle located in an adjacent molecule. Different parameters, such as radiative and non-radiative decay rates, quantum yield, electrical field enhancement factor, and fluorescence enhancement are calculated by such a model and they are compared with those obtained by using the classical Drude model. It is observed that using an analytical quantum model presents a higher enhancement factor, up to 30%, as compared to classical model for nanoparticles smaller than 10 nm. Furthermore, the results are in better agreement with those experimentally realized.
Effects of Indigenous Wood Specie and Plastic/Wood Ratio on Physicomechanical Properties of Wood Plastic Composites

As noted wood flour species plays an important role in the properties of the resulting composites. The effect of wood species as filler and reinforcement agent on physical and mechanical properties of the WPC was investigated. The used wood species in this study were Ceiba pentandra; Triplochiton scleroxylon and Entandrophragma cylindricum at plastic/wood ratio of 1:2.3, 1:1.5 and 1:1 (w/w). The physical and mechanical properties such as water absorption, thickness swelling, linear expansion, density, weight gained, flexural modulus and strength were tested. Entandrophragma cylindricum ranked highly in mechanical properties at plastic/wood ratio of 1:2.3, and more dimensionally stable at plastic/wood ratio of 1:1. As the wood content increases in the formulations of the composite, the increased in the flexural and decreased in dimensional stability of the composites produced. This observation follows the same trend in all the wood species employed for the production of composites tested. Based on the results, the guidelines information from this study could be used as a basis for WPC manufacture in tropical country like Nigeria.
Identifying patients at high risk of heparin-induced thrombocytopenia-associated thrombosis with a platelet activation assay using flow cytometry

Summary To diagnose heparin-induced thrombocytopenia (HIT), detection of platelet-activating antibodies (HIT antibodies) is crucial. However, serum platelet activation profiles vary across patients and depend on test conditions. We evaluated the association between clinical outcomes and platelet-activating profiles assessed by a platelet microparticle assay (PMA), which detects activation of washed platelets induced by HIT antibodies, in 401 consecutive patients clinically suspected of having HIT. We made modifications to the assay, such as donor selection for washed platelets that increased sensitivity. Serum that activated platelets at a therapeutic (but not high) heparin concentration was defined as positive. Of these, serum that activated platelets within 30 minutes or in the absence of heparin was defined as strongly positive. The remaining samples were considered weakly positive. As a result, 97 % and 93 % of patients who tested strongly and weakly positive had clinical profiles consistent with HIT, respectively. The incidence of thromboembolic events (TEEs) after heparin exposure in patients who tested strongly positive, weakly positive, and negative was 61 %, 40 %, and 29 %, respectively. Among patients who did not experience a TEE on the day HIT was suspected, there was no significant difference in the cumulative incidence of subsequent TEEs between patients who tested strongly and weakly positive when argatroban was initiated on the same day (19.0 % vs 7.1 %, p=0.313), but there was a significant difference when argatroban therapy was delayed by one or more days (61.1 % vs 17.6 %, p=0.007). The modified PMA is effective in diagnosing HIT and identifying patients at high risk for HIT-associated TEEs. Supplementary Material to this article is available online at www.thrombosis-online.com.
Assistive Mobile Manipulation : Designing for Operators with Motor Impairments Phillip

Individuals with severe motor impairments can operate mobile manipulators for physical assistance with activities of daily living. However, relatively little attention has been given to designing these systems with the explicit aim of reducing operator workload and increasing usability. This is especially important for operators with limited input bandwidth as a result of motor impairments. To address this challenge, we have worked regularly with Henry Evans, an individual with severe motor impairments, and Jane, his wife and primary caregiver. With their collaboration, we have developed an assistive robotic system that can be teleoperated via a modern web browser and a single-button mouse or equivalent. This increases accessibility for individuals with motor impairments already using assistive Human-Computer Interfaces. Our system uses a video-centric approach to reduce complexity, provides clear, easily switchable modes of interaction, and enables the use of task-level planning and task-relevant undo. We performed a preliminary evaluation of this system via remote operation by Henry Evans performing the Action Research Arm Test (ARAT), a clinical test for manipulation capability. In this evaluation, the system provided a clinically significant improvement relative to Henry’s own capability.
Clearance Prediction of Targeted Covalent Inhibitors by In Vitro-In Vivo Extrapolation of Hepatic and Extrahepatic Clearance Mechanisms

The concept of target-specific covalent enzyme inhibitors appears attractive from both an efficacy and a selectivity viewpoint considering the potential for enhanced biochemical efficiency associated with an irreversible mechanism. Aside from potential safety concerns, clearance prediction of covalent inhibitors represents a unique challenge due to the inclusion of nontraditional metabolic pathways of direct conjugation with glutathione (GSH) or via GSH S-transferase–mediated processes. In this article, a novel pharmacokinetic algorithm was developed using a series of Pfizer kinase selective acrylamide covalent inhibitors based on their in vitro-in vivo extrapolation of systemic clearance in rats. The algorithm encompasses the use of hepatocytes as an in vitro model for hepatic clearance due to oxidative metabolism and GSH conjugation, and the use of whole blood as an in vitro surrogate for GSH conjugation in extrahepatic tissues. Initial evaluations with clinical covalent inhibitors suggested that the scaling algorithm developed from rats may also be useful for human clearance prediction when species-specific parameters, such as hepatocyte and blood stability and blood binding, were considered. With careful consideration of clearance mechanisms, the described in vitro-in vivo extrapolation approach may be useful to facilitate candidate optimization, selection, and prediction of human pharmacokinetic clearance during the discovery and development of targeted covalent inhibitors.
Elite status maintained: a 12-year physiological and performance follow-up of two Olympic champion rowers

ABSTRACT This case study reports the results of a 12-year (2005–2016) follow-up study of two Olympic champion rowers. The rowers were prospective athletes at the junior level when the study began, and we monitored their relevant physiological and performance data annually. Our findings indicated that their V̇O2max gradually increased up to about 22 years of age and leveled off at a value of approximately 7 l·min−1 with minimal fluctuations thereafter. However, the variables that directly influence the V̇O2max changed. There was an age-related decline in maximal heart rate of about 0.5 beats·year−1, while oxygen pulse, which serves as an indirect measure of stroke volume, correspondingly increased by about 1 ml O2·beat−1 per year, allowing the athletes to maintain exceptional V̇O2max values. Maximal minute power of the studied rowers, derived each year from their ramp-wise tests, closely resembled the mean power output sustained during the 2000-m all-out tests on a rowing ergometer. A 12-year improvement of 28% and 33% occurred for the mean power output sustained over 2000 and 6000-m on a rowing ergometer, respectively. The findings contribute to the body of knowledge on athletes representing the true elites of their respective sports.
Wavelength Scanning with a Tilting Interference Filter for Glow-Discharge Elemental Imaging

Glow discharges have long been used for depth profiling and bulk analysis of solid samples. In addition, over the past decade, several methods of obtaining lateral surface elemental distributions have been introduced, each with its own strengths and weaknesses. Challenges for each of these techniques are acceptable optical throughput and added instrumental complexity. Here, these problems are addressed with a tilting-filter instrument. A pulsed glow discharge is coupled to an optical system comprising an adjustable-angle tilting filter, collimating and imaging lenses, and a gated, intensified charge-coupled device (CCD) camera, which together provide surface elemental mapping of solid samples. The tilting-filter spectrometer is instrumentally simpler, produces less image distortion, and achieves higher optical throughput than a monochromator-based instrument, but has a much more limited tunable spectral range and poorer spectral resolution. As a result, the tilting-filter spectrometer is limited to single-element or two-element determinations, and only when the target spectral lines fall within an appropriate spectral range and can be spectrally discerned. Spectral interferences that result from heterogeneous impurities can be flagged and overcome by observing the spatially resolved signal response across the available tunable spectral range. The instrument has been characterized and evaluated for the spatially resolved analysis of glow-discharge emission from selected but representative samples.
On the Emergence of Shadow IT - a Transaction Cost-Based Approach

Information Technology (IT) used for business processes is not only provided by the organization’s IT department. Business departments and users autonomously implement IT solutions, which are not embedded in the organizational IT service management. This increasingly occurring phenomenon is called Shadow IT. The various opportunities and risks of Shadow IT challenge organizations and call for approaches to manage the phenomenon. An initial point to achieve measurable indications for the management is to explain why Shadow IT emerges. Therefore, this paper explores the business decision to implement Shadow IT. Based on existing research we derive that Shadow IT is created after a make-or-buy decision, which is substantiated in the Transaction Cost Theory. We deploy a triangulation approach using the methods expert interviews and multiple-case study to investigate Shadow IT emergence. Our findings identify prohibitive transaction costs in the exchange relation between business and IT departments, influenced by misalignment, as the main explanation. We conclude that the principles of Transaction Cost Theory may be applied to develop governance structures for managing Shadow IT. This strengthens the link between IT Governance and Business IT Alignment and expands the understanding of business integration within the IT domains of an organization.
Estrus Induction Response and Fertility Performance in Delayed Pubertal Heifers Treated withAegle marmelosandMurraya koenigii

The present study was designed to examine the estrus induction response and fertility performance in delayed pubertal heifers treated with two medicinal plants Aegle marmelos in combination with Murraya koenigii. A total of 11 heifers were treated with the plants leaf powder for 9 days per orally after determining the dose by the extrapolation from effective dose of 50% ethanolic extract in rats (1000 mg/kg b. wt.) with optimum ovarian response. Extrapolated extract dose was subsequently converted to powder dose based on per cent yield. Six heifers were kept as untreated control. Six out of 11 (54.1%) heifers in treatment group and 1 out of 6 (16.7%) in control group exhibited standing estrus. All these estrus heifers were inseminated and confirmed as pregnant and calved in due course. Though the proportion of heifers that showed estrus, became pregnant and calved in the end, did not achieve statistical significance (P>0.05) between the groups, nevertheless, the number and proportion of such heifers was higher in the treatment group than that of control. In conclusion, the present study indicates that Aegle marmelos in combination with Murraya koenigii have the potential to induce estrus in delayed pubertal heifers with appreciable fertility performance.
Mechanical Properties of Vacuum Carbon-Deoxidized Thick-Wall 2¼Cr-1Mo Steel Forging

The effect of postweld heat treatment on the susceptibility to temper embrittlement of 2 1 / 4 Cr-1Mo steel forgings which have various silicon contents has been investigated. Then, to verify the validity of low-silicon 2 1 / 4 Cr-1Mo steel for an actual forging, the mechanical properties and the susceptibility to temper embrittlement of a 296-mm (11.7-in.)-thick forged ring made from a 100-ton ingot with silicon content reduced to below 0.10 percent by the vacuum carbon deoxidation (VCD) process have been tested. The results are as follows: (I) the through-thickness mechanical properties of the forging meet the requirements of ASME SA-336. F22; (2) silicon content has no significant effect on the creep-rupture strength at least to IS 000 h at 550°C (1022°F) and 600°C (1112°F); and (3) the susceptibility to embrittlement is very low, as the shift in 50 percent fracture appearance transition temperature is 14°C (25°F) for step cooling and 22°C (40°F) for isothermal treatment at 475°C (887°F) for 5000 h.
Effects of botulinum toxin A injections in spinal cord injury patients with detrusor overactivity and detrusor sphincter dyssynergia.

OBJECTIVE To evaluate the safety and effect of botulinum toxin A injection in the detrusor and external urethral sphincter in male patients with detrusor overactivity (DO) and detrusor external sphincter dyssynergia (DESD) secondary to spinal cord injury. METHODS A multicentre trial was conducted from June 2012 to August 2015. A total of 65 spinal cord injury patients with DO and DESD participated in the study. Of these, 59 received 200 U botulinum toxin Aintradetrusor and 100 U external urethral sphincter injections. The effective outcomes included maximum detrusor pressure at first DO and DESD, VDO-DESD, maximum urethral closure pressure, duration of first DO and DESD, Incontinence-Specific Quality-of-Life Instrument, voiding volume, urinary incontinence episodes and complete dryness. Adverse events were recorded. RESULTS All patients experienced a significant mean reduction in PdetmaxDO -DESD (46.60%), maximum urethral closure pressure (29.61%), duration of first DO and DESD (42.93%) and a significant mean increase in VDO-DESD (38.11%) 12-weeks post-injection. Significant (p < 0.001) improvement in mean Incontinence-Specific Quality-of-Life Instrument, voiding volume, urinary incontinence episodes and complete dryness were found in all patients at 2 weeks and were sustained at 8 weeks and 16 weeks. CONCLUSION Botulinum toxin A injection in the detrusor and external urethral sphincter is an effective treatment to protect the upper urinary tract and improve quality of life for patients with DO and DESD secondary to spinal cord injury.