Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility

The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded β-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate—and structurally plastic—layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated β-sandwich and providing for conformational diversity used in immune evasion. A “layered” gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a β-sandwich clamp maintains gp120–gp41 interaction and regulates gp41 transitions.
Development and psychometric evaluation of the Primary Health Care Engagement (PHCE) Scale: a pilot survey of rural and remote nurses

Aim To report the development and psychometric evaluation of a scale to measure rural and remote (rural/remote) nurses’ perceptions of the engagement of their workplaces in key dimensions of primary health care (PHC). Background Amidst ongoing PHC reforms, a comprehensive instrument is needed to evaluate the degree to which rural/remote health care settings are involved in the key dimensions that characterize PHC delivery, particularly from the perspective of professionals delivering care. Methods This study followed a three-phase process of instrument development and psychometric evaluation. A literature review and expert consultation informed instrument development in the first phase, followed by an iterative process of content evaluation in the second phase. In the final phase, a pilot survey was undertaken and item discrimination analysis employed to evaluate the internal consistency reliability of each subscale in the preliminary 60-item Primary Health Care Engagement (PHCE) Scale. The 60-item scale was subsequently refined to a 40-item instrument. Findings The pilot survey sample included 89 nurses in current practice who had experience in rural/remote practice settings. Participants completed either a web-based or paper survey from September to December, 2013. Following item discrimination analysis, the 60-item instrument was refined to a 40-item PHCE Scale consisting of 10 subscales, each including three to five items. Alpha estimates of the 10 refined subscales ranged from 0.61 to 0.83, with seven of the subscales demonstrating acceptable reliability (α⩾0.70). The refined 40-item instrument exhibited good internal consistency reliability (α=0.91). The 40-item PHCE Scale may be considered for use in future studies regardless of locale, to measure the extent to which health care professionals perceive their workplaces to be engaged in key dimensions of PHC.
Identification of the NS5B S282T Resistant Variant and Two Novel Amino Acid Substitutions That Affect Replication Capacity in Hepatitis C Virus-Infected Patients Treated with Mericitabine and Danoprevir

ABSTRACT Baseline and posttreatment samples from hepatitis C virus (HCV) genotype (GT) 1-infected patients who received a combination of danoprevir and mericitabine from a phase II clinical study (INFORM-SVR) were analyzed. In addition to resistance monitoring, sequencing and phenotypic assays were combined with statistical analysis to identify potential novel amino acid substitutions associated with treatment outcome. The NS5B S282T substitution associated with mericitabine resistance was identified in 2/30 viral breakthrough patients and was replaced by wild-type viruses after cessation of drug treatment (during follow-up). The NS3 R155K substitution associated with danoprevir resistance was also observed in these 2 patients. All 69 GT 1a-infected patients who experienced viral breakthrough on treatment or relapsed during follow-up (relapsers) developed NS3 R155K. Among GT 1b-infected patients, substitutions at the danoprevir resistance locus NS3 D168 were observed in 15/20 subjects, whereas substitutions at the danoprevir resistance locus NS3 R155 were observed in 5/20 subjects. Interestingly, the baseline polymorphism NS5B Q47H was more prevalent in GT 1a-infected patients who achieved a sustained virologic response at follow-up week 24 (SVR24) than in non-SVR24 patients (2/13 versus 0/72), and a postbaseline NS3 S122G substitution was more prevalent in GT 1a-infected patients with viral breakthrough than in relapsers (4/22 versus 0/47). Neither substitution conferred resistance to danoprevir or mericitabine, but the substitutions reduced (NS5B Q47H) or improved (NS3 S122G) replication capacity by 2- to 4-fold. The NS5B S282T mericitabine-resistant variant was rare and did not persist once drug was discontinued. NS5B Q47H and NS3 S122G are two newly identified substitutions that affected replication capacity and were enriched in distinct treatment response groups. (This study has been registered at ClinicalTrials.gov under registration no. NCT01278134.)
Association Between the Metabolome and Low Bone Mineral Density in Taiwanese Women Determined by 1H NMR Spectroscopy

Osteoporosis is related to the alteration of specific circulating metabolites. However, previous studies on only a few metabolites inadequately explain the pathogenesis of this complex syndrome. To date, no study has related the metabolome to bone mineral density (BMD), which would provide an overview of metabolism status and may be useful in clinical practice. This cross‐sectional study involved 601 healthy Taiwanese women aged 40 to 55 years recruited from MJ Health Management Institution between 2009 and 2010. Participants were classified according to high (2nd tertile plus 3rd tertile) and low (1st tertile) BMD groups. The plasma metabolome was evaluated by proton nuclear magnetic resonance spectroscopy (1H NMR). Principal components analysis (PCA), partial least‐squares discriminant analysis (PLS‐DA), and logistic regression analysis were used to assess the association between the metabolome and BMD. The high and low BMD groups could be differentiated by PLS‐DA but not PCA in postmenopausal women (Q2 = 0.05, ppermutation = 0.04). Among postmenopausal women, elevated glutamine was significantly associated with low BMD (adjusted odds ratio [AOR] = 5.10); meanwhile, elevated lactate (AOR = 0.55), acetone (AOR = 0.51), lipids (AOR = 0.04), and very low‐density lipoprotein (AOR = 0.49) protected against low BMD. To the best of our knowledge, this study is the first to identify a group of metabolites for characterizing low BMD in postmenopausal women using a 1H NMR–based metabolomic approach. The metabolic profile may be useful for predicting the risk of osteoporosis in postmenopausal women at an early age. © 2014 American Society for Bone and Mineral Research.
Security Fungibility and the Cost of Capital: Evidence from Global Bonds

Abstract This paper examines the potential benefits of security fungibility by conducting the first comprehensive analysis of global bonds. Unlike other debt securities, global bonds' fungibility allows them to be placed simultaneously in bond markets around the world; they trade, clear, and settle efficiently within as well as across markets. We test the impact of issuing these securities on firms' cost of capital, issuing costs, liquidity, and shareholder wealth. Using a sample of 230 global bond issues by 94 companies from the U.S. and abroad over the period 1996–2003, we find that firms lower their cost of (debt) capital by issuing these fungible securities. We also document that the stock price reaction to the announcement of global bond issuance is positive and significant, while comparable domestic and eurobond issues over the same time period are associated with insignificant changes in shareholder wealth.
N6-methyladenosine is required for the hypoxic stabilization of specific mRNAs

Post-transcriptional regulation of mRNA during oxygen deprivation, or hypoxia, can affect the survivability of cells. Hypoxia has been shown to increase stability of a subset of ischemia-related mRNAs, including VEGF. RNA binding proteins and miRNAs have been identified as important for post-transcriptional regulation of individual mRNAs, but corresponding mechanisms that regulate global stability are not well understood. Recently, mRNA modification by N6-methyladenosine (m6A) has been shown to be involved in post-transcriptional regulation processes including mRNA stability and promotion of translation, but the role of m6A in the hypoxia response is unknown. In this study, we investigate the effect of hypoxia on RNA modifications including m6A. Our results show hypoxia increases m6A content of poly(A)+ messenger RNA (mRNA), but not in total or ribosomal RNA in HEK293T cells. Using m6A mRNA immunoprecipitation, we identify specific hypoxia-modified mRNAs, including glucose transporter 1 (Glut1) and c-Myc, which show increased m6A levels under hypoxic conditions. Many of these mRNAs also exhibit increased stability, which was blocked by knockdown of m6A-specific methyltransferases METTL3/14. However, the increase in mRNA stability did not correlate with a change in translational efficiency or the steady-state amount of their proteins. Knockdown of METTL3/14 did reveal that m6A is involved in recovery of translational efficiency after hypoxic stress. Therefore, our results suggest that an increase in m6A mRNA during hypoxic exposure leads to post-transcriptional stabilization of specific mRNAs and contributes to the recovery of translational efficiency after hypoxic stress.
Analysis of the Foreign Sector as an Endogenous Variable in SAM Linear Models: An Empirical Proposal

La consideración tradicional del sector exterior como una variable exógena en los modelos lineales Input-Output y de Matrices de Contabilidad Social, ha dado lugar a estimaciones sesgadas de hipotéticas perturbaciones de la demanda en la aplicación de esos modelos. El objetivo de este trabajo es analizar la posibilidad de incluir las operaciones con el extranjero como una variable endógena, proponiendo una solución a las dificultades asociadas a esta opción. Por lo tanto, la metodología aquí propuesta hace posible evitar la sobrevaloración en el impacto del sector exterior, como ocurre cuando se estima con otras metodologías. Una Matriz de Contabilidad Social de España se ha utilizado como base de datos para este trabajo.
Simultaneous genetic evaluation of sires and cows for a large population of dairy cattle.

A strategy for simultaneous sire and cow evaluation of genetic merit was implemented. First lactation records of 1,074,971 Holstein cows in 20,065 herds were included. After inclusion of ancestors, there were 1,741,356 equations: 1,505,938 cow, 229,394 herd-year-season, 6000 sire, and 24 genetic group equations. All known genetic relationships among animals were considered. Genetic group coefficients were assigned based on animals that had one or more parents unidentified. Mixed model equations from an animal model were transformed to solve for total additive genetic merit. The coefficient matrix was sparse with . 00039% nonzero elements. Equations were blocked by herds. A final block included sires, groups, and cows that had no daughters or records. Effects of herd-year-season were solved last within each herd. All herd blocks were solved before sire equations. A form of block iteration with successive overrelaxation was used to obtain solutions. A total of 30 rounds were completed. Number of iterations per round for herd blocks decreased from an average of 4.93 in round 1 to the minimum allowed, 3.00, in round 30. The correlation between Northeast Artificial Insemination Sire Comparisons and sire solutions from this study stabilized at . 94. At round 30, 96.4, 95.2, 99.4, and 75.0% of solutions for cow, sire, herd-year-season, and group effects changed less than 4.54 kg from the previous round.
Human Psychology of Common Appraisal: The Reddit Score

The Reddit score reflects a common appraisal by a community of Reddit subscribers of a submitted item, called a story. The general random walk with random maximum boundary is demonstrated to describe the distribution function of the Reddit score of an arbitrary story in the online social news aggregator Reddit.com. Exponential tails, predicted by the analysis, are observed, while a curious intermediate “power law-like” region seems to correspond to a remarkable empirical observation that the total number of downvotes depends in “power law” fashion on the total number of upvotes. Stronger even, those downvotes increase faster than the upvotes, which is a surprising fact that asks for a (socio-psychological? ) explanation.
New Insights on the Mechanisms of Disease Course Variability in ALS from Mutant SOD1 Mouse Models

Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous disease in terms of progression rate and survival. This is probably one of the reasons for the failure of many clinical trials and the lack of effective therapies. Similar variability is also seen in SOD1G93A mouse models based on their genetic background. For example, when the SOD1G93A transgene is expressed in C57BL6 background the phenotype is mild with slower disease progression than in the 129Sv mice expressing the same amount of transgene but showing faster progression and shorter lifespan. This review summarizes and discusses data obtained from the analysis of these two mouse models under different aspects such as the motor phenotype, neuropathological alterations in the central nervous system (CNS) and peripheral nervous system (PNS) and the motor neuron autonomous and non‐cell autonomous mechanisms with the aim of finding elements to explain the different rates of disease progression. We also discuss the identification of promising prognostic biomarkers by comparative analysis of the two ALS mouse models. This analysis might possibly suggest new strategies for effective therapeutic intervention in ALS to slow significantly or even block the course of the disease.
6D Object Pose Estimation with Depth Images: A Seamless Approach for Robotic Interaction and Augmented Reality

To determine the 3D orientation and 3D location of objects in the surroundings of a camera mounted on a robot or mobile device, we developed two powerful algorithms in object detection and temporal tracking that are combined seamlessly for robotic perception and interaction as well as Augmented Reality (AR). A separate evaluation of, respectively, the object detection and the temporal tracker demonstrates the important stride in research as well as the impact on industrial robotic applications and AR. When evaluated on a standard dataset, the detector produced the highest f1-score with a large margin while the tracker generated the best accuracy at a very low latency of approximately 2 ms per frame with one CPU core: both algorithms outperforming the state of the art. When combined, we achieve a powerful framework that is robust to handle multiple instances of the same object under occlusion and clutter while attaining real-time performance. Aiming at stepping beyond the simple scenarios used by current systems, often constrained by having a single object in absence of clutter, averting to touch the object to prevent close-range partial occlusion, selecting brightly colored objects to easily segment them individually or assuming that the object has simple geometric structure, we demonstrate the capacity to handle challenging cases under clutter, partial occlusion and varying lighting conditions with objects of different shapes and sizes.
Clinical Governance and evidence-based laboratory medicine

Abstract Background: Clinical Governance is described as “a framework through which the NHS organisations are accountable to continue to improve the quality of the service and safeguarding high standards of care by creating an environment in which excellence in clinical care would flourish”; it is aimed to ensure continuous improvement in the overall standard of clinical care, ensuring that clinical decisions are based on the most up-to-date evidence in terms of effectiveness. Methods: If Clinical Governance is a framework through which NHS organisations are accountable to continuously improve the quality of their services and safeguarding high standards of care, Clinical Effectiveness is a vital part of Clinical Governance. Clinical Effectiveness is a term that refers to measuring and monitoring the quality of care, and comprises various activities, including: Evidence-Based Practice, Research and Development, Clinical Audit, Clinical Guidelines, Integrated Care Pathways, and Total Quality Management. Results: The application of evidence-based medicine (EBM) in laboratory medicine or evidence-based laboratory medicine (EBLM) aims to advance clinical diagnosis by researching and spreading new knowledge, combining methods from clinical epidemiology, statistics and social science with the traditional pathophysiological molecular approach. EBLM, by evaluating the role of diagnostic investigations in the clinical decision-making process, can help in translating the results of good quality research into everyday practice. Conclusions: If Clinical Governance is a framework through which organisations are accountable to improve the quality of care, health professionals should identify high quality standards, and systematically and rigorously monitor against them the process and outcomes that represent the diagnostic process. Within such a policy framework, practice guidelines are expected to play a major role, providing the basis to access the quality of care and guidance where clinical practice is found not in line with professional standards.
Soft real-time traffic communication in loaded Wireless Mesh Networks

Industrial applications have been shifting towards wireless multi-hop networks in recent years due to their lower cost of deployment and reconfiguration compared with their wired counterparts. These wireless networks usually must support real-time communication to meet the application requirements. For this reason, Wireless Mesh Networks (WMNs) are potential candidates for industrial applications as they support a fixed infrastructure of static nodes for relaying packets. To meet the application demands, we modify the wireless chain network protocol (WICKPro) to support soft real-time traffic in WMNs with chain topologies over IEEE 802.11. We employ tele-operation of mobile robots as our case study, and perform extensive simulation and laboratory experiments. We show that the data delivery ratio is increased up to 42% in a scenario with 7 nodes, when the maximum end-to-end delay tolerated by the application is doubled. This is particularly suited to soft real-time applications that can trade longer delays by higher reliability. Moreover, when compared with a distributed priority-based token-passing protocol (RT-WMP), the lower overhead of WICKPro allows, in an error-free scenario, obtaining a throughput improvement of 33.42% on average.
Why Men and Women Want to Leave? Turnover Intent Among Public Procurement Officers

This study examines differences in turnover intent between men and women with the aim of building a better understanding of factors that contribute to disparities between the sexes and creating more useful recruitment and retention strategies. The study proposes a theoretical framework where personal, human capital, organizational, and structural/community factors contribute to the desire to change jobs. The focus here is on procurement officers as their role is critical in public sector organizations from the local to the federal level. They also are unique in that their skill set is transferable from one organization to another and procurement officers have relatively high opportunities to move both within and between organizations. The study finds that there are important differences in the drivers of turnover intent between men and women and that most differences lie in the personal, human capital, and organizational categories.
The Impact of Acquiring Unrestricted Work Authorization on Romanian and Bulgarian Migrants in the United Kingdom

When Romania and Bulgaria (the so-called A2 countries) joined the European Union in 2007, the United Kingdom imposed temporary restrictions on the employment and welfare entitlements of A2 citizens that lasted until January 1, 2014. This article analyzes the impact of the removal of these restrictions on the labor market outcomes and use of welfare benefits of A2 migrants. Applying difference-in-difference analysis to data from the UK’s Labour Force Survey, the results suggest that acquiring unrestricted work authorization had a significant negative impact on the incidence of self-employment among A2 migrants but there are no discernible effects on other labor market outcomes or on their receipt of a range of welfare benefits. The article offers potential explanations for these results.
Apoptosis induced by high-LET radiations is not affected by cellular p53 gene status

To learn more about the biological effects of high-linear energy transfer (LET) radiations, we examined radiation-induced apoptosis in response to high-LET radiations in cells with wild-type, mutated and null p53 gene. Three human lung cancer cell lines were used. These lines had identical genotypes, except for the p53 gene. Cells were exposed to X-rays or high-LET radiations (13 – 200 keV μm−1) using different nuclei ion beams. Cellular radiation sensitivities were determined with the use of colony-forming assays. Apoptosis was detected and quantified using Hoechst 33342 staining with fluorescence microscopy. It was found that (1) there was no significant difference in cellular sensitivity to high-LET radiation (>85 keV μm−1), although the sensitivity of wild-type p53 cells to X-rays was higher than that of mutated p53 or p53-null cells; (2) X-ray-induced apoptosis at higher frequencies in wild-type p53 cells when compared with mutated p53 and p53-null cells; and (3) Fe beams (200 keV μm−1) induced apoptosis in a p53-independent manner. The results indicate that high-LET radiations induces apoptosis in human lung cancer cells in a manner that does not seem to depend on the p53 gene status of the cells.