Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteinases and plaque rupture: unblocking the road to translation

Purpose of review To review progress over the past 5 years in relating extracellular proteinases to plaque rupture, the cause of most myocardial infarctions, and consider the most promising prospects for developing related treatments. Recent findings Cysteinyl cathepsins have been implicated in multiple macrophage functions that could promote plaque rupture. Cathepsin K is an attractive target because it is a collagenase and selective inhibitors are already being used in phase III clinical trials. Several serine proteinases clearly influence vascular remodelling and atherogenesis but important, unrelated actions limit their value as therapeutic targets. Among the metalloproteinases, new evidence supports roles for A Disintigrin and Metalloproteinases (ADAMs), including ADAM-10, ADAM-17 and ADAM-33, which suggest that selective inhibitors might be effective treatments. For ADAMs with ThromboSpondin domains (ADAMTSs), there are biological and genome-wide association data linking ADAMTS-7 to incidence of coronary heart disease but not increased risk of myocardial infarctions. In the case of matrix metalloproteinases (MMPs), selective inhibitors of MMP-12 and MMP-13 are available and may be appropriate for development as therapies. Novel targets, including MMP-8, MMP-10, MMP-14, MMP-19, MMP-25 and MMP-28, are also being considered. Summary New opportunities exist to exploit proteinases as therapeutic targets in plaque rupture.
Circulating cell-free DNA in plasma/serum of lung cancer patients as a potential screening and prognostic tool.

BACKGROUND Evaluation of tumor-specific circulating DNA in plasma/serum is a promising noninvasive diagnostic and prognostic tool requiring only a blood sample, which circumvents the logistic difficulties associated with the use of invasive procedures for serial tumor samplings during screening of lung cancer. METHODS We reviewed English-language reports published in the MEDLINE database that provided the results of qualitative and quantitative studies on circulating DNA in serum/plasma of lung cancer patients. We searched the bibliographies of the retrieved reports and reviews. Abstracts presented at the 2003, 2004, and 2005 annual meetings of the American Society of Clinical Oncology were also reviewed. RESULTS More than 80 citations were retrieved, of which 33 met our criteria: 22 qualitative studies, and 11 quantitative studies. The studies varied in the choice of markers, frequency of alterations, sensitivities of used methodologies, sample sizes, treatment protocols, and prognostic correlates evaluated. CONCLUSIONS The findings from the studies on serum/plasma DNA suggest that it would be possible to develop a simple blood test with high sensitivity and specificity that has potential for screening of high-risk individuals, for prognostic or staging purposes, and to be used as intermediate end-points of efficacy in chemo-prevention and therapeutic trials. However, further work is needed to identify additional biomarkers and to standardize present techniques for sample collection, processing, and analysis. Large prospective studies with long follow-ups are essential to eventually integrate blood marker-based assays into the clinical setting.
The cellular receptor to human rhinovirus 2 binds around the 5‐fold axis and not in the canyon: a structural view

Human rhinovirus serotype 2 (HRV2) belongs to the minor group of HRVs that bind to members of the LDL‐receptor family including the very low density lipoprotein (VLDL)‐receptor (VLDL‐R). We have determined the structures of the complex between HRV2 and soluble fragments of the VLDL‐R to 15 Å resolution by cryo‐electron microscopy. The receptor fragments, which include the first three ligand‐binding repeats of the VLDL‐R (V1–3), bind to the small star‐shaped dome on the icosahedral 5‐fold axis. This is in sharp contrast to the major group of HRVs where the receptor site for ICAM‐1 is located at the base of a depression around each 5‐fold axis. Homology models of the three domains of V1–3 were used to explore the virus–receptor interaction. The footprint of VLDL‐R on the viral surface covers the BC‐ and HI‐loops on VP1.
A Distributed Voltage Controlled Oscillator in a standard 65nm CMOS Process

This paper presents the design of a distributed voltage controlled oscillator (DVCO). This oscillator has been designed in a low-cost low-power standard STMicroelectronics 65nm CMOS process. The DVCO achieves a tuning range from 9.6GHz to 11.6GHz, a phase noise better than -101dBc/Hz at 1MHz offset from the carrier and a total power consumption of 29mW
Do victims of crime fear crime more? Empirical evidence from the Survey of Living Conditions (2005) of Trinidad and Tobago

[1] Department of Economics, The University of the West Indies, St. Augustine, Trinidad and Tobago. [2] Loughborough University Business School, Loughborough, Leicestershire, LE11 3TU, United Kingdom. [3] The Sir Arthur Lewis Institute of Social and Economic Studies, The University of the West Indies, St. Augustine, Trinidad and Tobago. This paper uses micro-level data from the Survey of Living Conditions (2005) to examine an ongoing research question related to whether the victims of crime fear crime more than non-victims. To a lesser extent, we also explore some of the social and economic factors that impacts on an individual’s fear of crime through the use of probit models. Our results indicate that people's fear of crime does appear to reflect whether they themselves were victims of crime. However, we go beyond the existing literature to suggest that victimization matters when individuals did not report the crime to the police or reported it but action was not taken. Thus, our study has direct policy implications on the role of the police effectiveness in reducing fear of crime.
Brief Report: High HIV Incidence in a South African Community of Men Who Have Sex With Men: Results From the Mpumalanga Men's Study, 2012–2015

Abstract:Cross-sectional studies among African men who have sex with men (MSM) populations demonstrate high HIV prevalence, but few incidence estimates exist. The Mpumalanga Men's Study in Gert Sibande, Mpumalanga province, South Africa, involved 3 serial cross-sectional surveys of MSM recruited through respondent-driven sampling between 2012 and 2015. Successive surveys recaptured a nested cohort of 179, contributing 144.3 person-years (PY) of observation. We observed 18 seroconversions, or incidence of 12.5/100 (PY) (95% confidence interval CI: 8.1 to 19.2/100 PY). Presumptions of high incidence among MSM were confirmed and demonstrate an urgent need for biomedical prevention and treatment programming for MSM in South Africa.
The Architectural Design of Globe: A Wide-Area Distributed System

Article summary. Developing large-scale wide-area applications requires an infrastructure that is presently lacking. Currently, most Internet applications have to be built on top of raw communication services, such as TCP connections. All additional services, including those for naming, replication, migration, persistence, fault tolerance, and security, have to be implemented for each application anew. Not only is this a waste of effort, it also makes interoperability between different applications difficult or even impossible. The authors present a novel, object-based framework for developing widearea distributed applications. The framework is based on the concept of a distributed shared object, which has the characteristic feature that its state can be physically distributed across multiple machines at the same time. All implementation aspects, including communication protocols, replication strategies, and distribution and migration of state, are part of each object and are hidden behind its interface. The current performance problems of the World-Wide Web are taken as an example to illustrate the benefit of encapsulating state, operations, and implementation strategies on a per-object basis. The authors describe how distributed objects can be used to implement worldwide scalable Web documents.
Schistosomiasis in the People's Republic of China: Prospects and Challenges for the 21st Century

SUMMARY Schistosomiasis japonica is a serious communicable disease and a major disease risk for more than 30 million people living in the tropical and subtropical zones of China. Infection remains a major public health concern despite 45 years of intensive control efforts. It is estimated that 865,000 people and 100,250 bovines are today infected in the provinces where the disease is endemic, and its transmission continues. Unlike the other schistosome species known to infect humans, the oriental schistosome, Schistosoma japonicum, is a true zoonotic organism, with a range of mammalian reservoirs, making control efforts extremely difficult. Clinical features of schistosomiasis range from fever, headache, and lethargy to severe fibro-obstructive pathology leading to portal hypertension, ascites, and hepatosplenomegaly, which can cause premature death. Infected children are stunted and have cognitive defects impairing memory and learning ability. Current control programs are heavily based on community chemotherapy with a single dose of the drug praziquantel, but vaccines (for use in bovines and humans) in combination with other control strategies are needed to make elimination of the disease possible. In this article, we provide an overview of the biology, epidemiology, clinical features, and prospects for control of oriental schistosomiasis in the People's Republic of China.
A study model with spacing and test effect

How to study more efficiently and maintain the lasting memory of knowledge has long been a contentious hot focus, particularly in the education of Internet era such as the massive open online Courses. Recently, many researchers have pointed out that studying and remembering have good spacing effect, and proposed various models including the effect. However, it does not consider the importance of testing in learning. In this paper, we proposed a new study model which combining with spacing effect and testing to construct a studying and scheduling sequence for different level students. The model consists of studying units, reviewing units and testing units, and can be parameterized to better adapt to the studying ability and the learning progress for diverse students. Example and experiments are given to illustrate and verified the ideas.
Dynamic Architectural Selection: A Genetic Algorithm Based Approach

As the software industry is focusing on dealing with various requirements and environments, such as mobile and ubiquitous environments, software systems are increasingly undergoing many situational changes. These changes influence the quality of services that the software provides. Therefore, to maintain the performance of the software, it must be reconfigured. The reconfiguration is a complex problem if an application faces a large number of situations and has a number of software architectural instances. In this paper, we propose a novel approach to autonomous architectural selection in response to the current situation of various environments. This approach enables a software system to determine the best architectural instance for the current situation. To quickly find the best instance, we apply a genetic algorithm to the selection process. Further, we provide a performance evaluation to demonstrate that our approach efficiently find the best instance (or considerably good instance).
Orbital tests of relativistic gravity using artificial satellites.

We reexamine non-Einsteinian effects observable in the orbital motion of low-orbit artificial Earth satellites. The motivations for doing so are twofold: (i) recent theoretical studies suggest that the correct theory of gravity might contain a scalar contribution which has been reduced to a small value by the effect of the cosmological expansion; (ii) presently developed space technologies should soon give access to a new generation of satellites endowed with drag-free systems and tracked in three dimensions at the centimeter level. Our analysis suggests that such data could measure two independent combinations of the Eddington parameters (beta - 1) and (gamma - 1) at the 10^-4 level and probe the time variability of Newton's "constant" at the d(ln G)/dt ~ 10^-13 yr^-1 level. These tests would provide well-needed complements to the results of the Lunar Laser Ranging experiment, and of the presently planned experiments aiming at measuring (gamma -1). In view of the strong demands they make on the level of non- gravitational perturbations, these tests might require a dedicated mission consisting of an optimized passive drag-free satellite.
Isolation of Vaginal Lactobacilli and Characterization of Anti-Candida Activity

Healthy vaginal microbiota is dominated by Lactobacillus spp. , which form a critical line of defence against pathogens, including Candida spp. The present study aims to identify vaginal lactobacilli exerting in vitro activity against Candida spp. and to characterize their antifungal mechanisms of action. Lactobacillus strains were isolated from vaginal swabs of healthy premenopausal women. The isolates were taxonomically identified to species level (L. crispatus B1-BC8, L. gasseri BC9-BC14 and L. vaginalis BC15-BC17) by sequencing the 16S rRNA genes. All strains produced hydrogen peroxide and lactate. Fungistatic and fungicidal activities against C. albicans, C. glabrata, C. krusei, C. tropicalis, C. parapsilosis and C. lusitaniae were evaluated by broth micro-dilution method. The broadest spectrum of activity was observed for L. crispatus BC1, BC4, BC5 and L. vaginalis BC15, demonstrating fungicidal activity against all isolates of C. albicans and C. lusitaniae. Metabolic profiles of lactobacilli supernatants were studied by 1H-NMR analysis. Metabolome was found to be correlated with both taxonomy and activity score. Exclusion, competition and displacement experiments were carried out to investigate the interference exerted by lactobacilli toward the yeast adhesion to HeLa cells. Most Lactobacillus strains significantly reduced C. albicans adhesion through all mechanisms. In particular, L. crispatus BC2, L. gasseri BC10 and L. gasseri BC11 appeared to be the most active strains in reducing pathogen adhesion, as their effects were mediated by both cells and supernatants. Inhibition of histone deacetylases was hypothesised to support the antifungal activity of vaginal lactobacilli. Our results are prerequisites for the development of new therapeutic agents based on probiotics for prophylaxis and adjuvant therapy of Candida infection.
Combining Information from Ancestors and Personal Experiences to Predict Individual Differences in Developmental Trajectories

A persistent question in biology is how information from ancestors combines with personal experiences over the lifetime to affect the developmental trajectories of phenotypic traits. We address this question by modeling individual differences in behavioral developmental trajectories on the basis of two assumptions: (1) differences among individuals in the behavior expressed at birth or hatching are based on information from their ancestors (via genes, epigenes, and prenatal maternal effects), and (2) information from ancestors is combined with information from personal experiences over ontogeny via Bayesian updating. The model predicts relationships between the means and the variability of the behavior expressed by neonates and the subsequent developmental trajectories of their behavior when every individual is reared under the same environmental conditions. Several predictions of the model are supported by data from previous studies of behavioral development, for example, that the temporal stability of personality will increase with age and that the intercepts and slopes of developmental trajectories for boldness will be negatively correlated across individuals or genotypes when subjects are raised in safe environments. We describe how other specific predictions of the model can be used to test the hypothesis that information from ancestors and information from personal experiences are combined via nonadditive, Bayesian-like processes.
Mutation-Driven β-Lactam Resistance Mechanisms among Contemporary Ceftazidime-Nonsusceptible Pseudomonas aeruginosa Isolates from U.S. Hospitals

ABSTRACT OprD loss and hyperexpression of AmpC, MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM were evaluated among 120 Pseudomonas aeruginosa isolates collected during 2012 in U.S. hospitals and selected based on ceftazidime MIC values (1 to >32 μg/ml). AmpC derepression (10-fold greater than that with the control) and OprD loss (decreased/no band) were the most prevalent resistance mechanisms: 47.5 and 45.8% of the isolates were considered positive, respectively. Elevated expression of the efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was observed in 32.5, 8.3, 0.0, and 28.4% of the isolates, respectively. A total of 21 different combinations of resistance mechanisms were noted, and the most prevalent included AmpC derepression with OprD loss with and without efflux hyperexpression (38 and 10 isolates, respectively). A total of 26 isolates had no changes in the resistance mechanisms tested and had lower MIC values for all β-lactams or β-lactam/β-lactamase inhibitor combinations analyzed. OprD loss had a strong correlation with elevated MIC results for imipenem and meropenem (median MIC values of 8 and 4 μg/ml, respectively), with all combinations displaying OprD loss also displaying elevated median MIC values for these carbapenems (4 to >8 μg/ml). AmpC expression levels were greater in isolates displaying elevated cefepime, ceftazidime, or piperacillin-tazobactam MIC values (≥4, ≥4, and ≥16 μg/ml, respectively). Isolates displaying derepressed AmpC had ceftolozane-tazobactam MIC values ranging from 1 to 16 μg/ml. No strong correlation was noticed with MIC values for this β-lactam/β-lactamase inhibitor combination and OprD loss or hyperexpression of efflux systems. Two KPC-producing isolates were detected among 16 isolates displaying ceftolozane-tazobactam MIC values of ≥8 μg/ml.
The greening of Protestant thought

The Greening of Protestant Thought traces the increasing influence of environmentalism on American Protestantism since the first Earth Day, which took place in 1970. Robert Booth Fowler explores the extent to which ecological concerns permeate Protestant thought and examines contemporary controversies within and between mainline and fundamentalist Protestantism over the Bible's teachings about the environment. Fowler explores the historical roots of environmentalism in Protestant thought, including debates over God's relationship to nature and the significance of the current environmental crisis for the history of Christianity. Although he argues that mainline Protestantism is becoming increasingly 'green,' he also examines the theological basis for many fundamentalists' hostility toward the environmental movement. In addition, Fowler considers Protestantism's policy agendas for environmental change, as well as the impact on mainline Protestant thinking of modern eco-theologies, process and creation theologies, and ecofeminism.
Cryptogenic cirrhosis: metabolic liver disease due to insulin resistance.

OBJECTIVE Etiopathogenesis of cryptogenic cirrhosis (CC) is not yet well established. Up to 20% of non-alcoholic fatty liver disease (NAFLD) may progress to cirrhosis, mostly termed as cryptogenic. Insulin resistance and altered metabolic parameters form a major pathogenic link between NAFLD and CC. CC may thus be actually a metabolic liver disease. MATERIALS AND METHODS Thirty-four patients of CC and 32 patients having cirrhosis due to chronic hepatitis B (Hep B) were assessed in a cross-sectional study in a tertiary hospital for insulin resistance, % β-cell activity, obesity indices, plasma glucose, lipid profiles, and many other parameters. RESULTS CC patients had higher homeostasis model assessment (HOMA)-IR compared to Hep B group (P = 0.000016). A positive correlation between IR values and Child-Pugh score among CC patients was found ("r" = 0.87; P < 0.00001). Out of 34 CC patients, 15 (44.1%) had obesity contrary to 6 (18.8%) in the control group (P = 0.0022). Differences were observed in subcutaneous fat (P = 0.0022), intra-abdominal fat (P = 0.0055), waist circumference (P = 0.014), and percentage body fat (P = 0.047) between the two groups. Significant differences were observed in the levels of triglyceride, total cholesterol, and very low density lipoprotein (VLDL). CONCLUSION Most of the CC patients showed significantly higher prevalence of HOMA-IR, obesity indices, and various parameters of "lipotoxicity" and metabolic syndrome, suggesting that CC may be the long-term consequence of a type of "metabolic liver disease. " Further studies are required to evaluate the role of therapeutic interventions to enhance insulin sensitivity in such patients.
The Determinants of Students’ Perceived Learning Outcomes and Satisfaction in University Online Education: An Update*

A stream of research over the past decade that identifies predictors of e-learning success suggests that there are several critical success factors (CSFs) that must be managed effectively to fully realize promise for e-learning. Grounded in constructivist learning theories, this study advances previous work on CSFs in university online education. Structural equation modeling is applied to examine the determinants of students’ satisfaction and their perceived learning outcomes in the context of university online courses. The independent variables of motivation (intrinsic and extrinsic), student self-regulation, dialogue (instructor-student, and student-student), instructor, and course design are examined as potential determinants of online learning outcomes. A total of 372 responses from students who have completed at least one online course at a university in the Midwestern United States were used to examine the structural model. Findings indicate that instructor-student dialogue, student-student dialogue, instructor, and course design significantly affect students’ satisfaction and learning outcomes. However, both extrinsic student motivation and student self-regulation have no significant relationship with user satisfaction and learning outcomes. Finally, intrinsic student motivation affects learning outcomes but not user satisfaction. The findings suggest that course design, instructor, and dialogue are the strongest predictors of user satisfaction and learning outcomes.