Miracle-dz/UniFAR-FTUs huggingface dataset:
Mucosal Tissue Tropism and Dissemination of HIV-1 Subtype B Acute Envelope-Expressing Chimeric Virus

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) transmission results from infection with one or a small number of variants from the donor quasispecies. Transmitted/founder (T/F) viruses have recently been identified from acutely infected patients, but the way in which they interact with primary targets of HIV-1 infection is poorly understood. We have conducted a biological characterization of a panel of subtype B T/F acute and chronic envelope (Env)-expressing chimeric virus in primary human target cells and mucosal tissues. Both acute and chronic Envs preferentially replicated in peripheral blood mononuclear cells (PBMC) and a CD4 T-cell line compared to monocyte-derived macrophages, or dendritic cells (DC). In a model of trans infection from monocyte-derived dendritic cells to T cells, chimeric virus from acute Envs achieved significantly lower titers compared to chronic Envs. Challenge of primary human mucosal tissues revealed significantly higher levels of replication in chronic Env-expressing virus in rectal tissue compared to cervical and penile tissues and enhanced replication in tonsillar tissue relative to acute Envs. In agreement with data from the DC to T-cell trans infection assay, chronic Env-chimeric virus pools were transmitted more efficiently by migratory cells from cervical and penile tissues to CD4+ T cells than individual acute Env chimeras. These data indicate that virus with HIV-1 Envs of transmitted acute infections preferentially replicate in T cells rather than macrophages or dendritic cells and are less efficiently transmitted from antigen-presenting cells to CD4 T cells than chronic Envs. Such properties together with chemokine (C-C motif) receptor 5 (CCR5) use may confer an advantage for transmission.
NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: the International Collaborative of NT-proBNP Study.

AIMS Experience with amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing for evaluation of dyspnoeic patients with suspected acute heart failure (HF) is limited to single-centre studies. We wished to establish broader standards for NT-proBNP testing in a study involving four sites in three continents. METHODS AND RESULTS Differences in NT-proBNP levels among 1256 patients with and without acute HF and the relationship between NT-proBNP levels and HF symptoms were examined. Optimal cut-points for diagnosis and prognosis were identified and verified using bootstrapping and multi-variable logistic regression techniques. Seven hundred and twenty subjects (57.3%) had acute HF, whose median NT-proBNP was considerably higher than those without (4639 vs. 108 pg/mL, P<0.001), and levels of NT-proBNP correlated with HF symptom severity (P=0.008). An optimal strategy to identify acute HF was to use age-related cut-points of 450, 900, and 1800 pg/mL for ages <50, 50-75, and >75, which yielded 90% sensitivity and 84% specificity for acute HF. An age-independent cut-point of 300 pg/mL had 98% negative predictive value to exclude acute HF. Among those with acute HF, a presenting NT-proBNP concentration >5180 pg/mL was strongly predictive of death by 76 days [odds ratio=5.2, 95% confidence interval (CI)=2.2-8.1, P<0.001]. CONCLUSION In this multi-centre, international study, NT-proBNP testing was valuable for diagnostic evaluation and short-term prognosis estimation in dyspnoeic subjects with suspected or confirmed acute HF and should establish broader standards for use of the NT-proBNP in dyspnoeic patients.
Speed control of brushless DC motor drive employing hard chopping PWM technique using DSP

This paper presents the speed control of brushless dc motor drive employing hard chopping PWM technique using TMS320F240 digital signal processor. BLDC is widely used because of its high mechanical power density, simplicity and cost effectiveness. The complete controller for BLDC is developed using TMS 320F240 digital signal processor, which has the special features for digital motor control. The three hall sensor signals are used to sense the rotor position. A shunt resistor is used to sense the actual current entering into the motor. These three hall signals, phase current sensing signal and the speed command are the input to the DSP. Both the outer velocity control loop and inner current control loop uses PI controller that has been implemented by programming in TMS320F240 DSP processor. According to the input command, feedback command and control algorithm, the PWM pulses for each phase generated by the DSP is given to MOSFET driver. The output of the driver is 6 independent PWM pulses that has to be given to the corresponding gate of the six MOSFET power switches used in the three-phase bridge inverter whose output is given to the stator of the BLDC motor.
27.5 A 4GS/s time-interleaved RF ADC in 65nm CMOS with 4GHz input bandwidth

The performance and power consumption of high-speed ADCs has advanced such that some receiver architectures can directly sample the input without down-conversion. This work looks to extend the applicability of such high-speed ADCs by digitizing wireless communications bands up to 4GHz with a high level of spectral purity. Fabricated in foundry 65nm CMOS and operating up to 4GS/s with power consumption of 2.2W, the reported ADC achieves noise performance of over 60dBFS and linearity performance of 64dBc at 1.842GHz input frequency. At 3.8GHz input frequency, SNR is dominated by aperture jitter of 50fs and two-tone IMD3 is >60dBFS.
Cathepsin K, but Not Cathepsins B, L, or S, Is Abundantly Expressed in Human Osteoclasts (*)

Random high throughput sequencing of a human osteoclast cDNA library was employed to identify novel osteoclast-expressed genes. Of the 5475 ESTs obtained, approximately 4% encoded cathepsin K, a novel cysteine protease homologous to cathepsins S and L; ESTs for other cathepsins were rare. In addition, ESTs for cathepsin K were absent or at low frequency in cDNA libraries from numerous other tissues and cells. In situ hybridization in osteoclastoma and osteophyte confirmed that cathepsin K mRNA was highly expressed selectively in osteoclasts; cathepsins S, L, and B were not detectable. Cathepsin K was not detected by in situ hybridization in a panel of other tissues. Western blot of human osteoclastoma or fetal rat humerus demonstrated bands of 38 and 27 kDa, consistent with sizes predicted for pro- and mature cathepsin K. Immunolocalization in osteoclastoma and osteophyte showed intense punctate staining of cathepsin K exclusively in osteoclasts, with a polar distribution that was more intense at the bone surface. The abundant expression of cathepsin K selectively in osteoclasts strongly suggests that it plays a specialized role in bone resorption. Furthermore, the data suggest that random sequencing of ESTs from cDNA libraries is a valuable approach for identifying novel cell-selective genes.
Reduced large elastic artery stiffness with regular aerobic exercise in middle-aged and older adults: potential role of suppressed nuclear factor &kgr; B signalling

Objective: Aortic pulse-wave velocity (aPWV) increases with age and is a strong independent predictor of incident cardiovascular diseases (CVDs) in healthy middle-aged and older adults. aPWV is lower in middle-aged and older adults who perform regular aerobic exercise than in their sedentary peers. As exercise is associated with reduced systemic inflammation, we hypothesized that suppression of the pro-inflammatory transcription factor nuclear factor &kgr; B (NF&kgr;B) may mediate this process. Methods: aPWV was measured in young sedentary [n = 10, blood pressure (BP) 108 ± 3/59 ± 2 mmHg; mean ± SEM], middle-aged and older sedentary (n = 9, 124 ± 7/73 ± 5 mmHg) and middle-aged and older aerobic exercise-trained (n = 12, 110 ± 4/67 ± 2 mmHg) healthy, nonhypertensive men and women. Results: Baseline aPWV increased with age [626 ± 14 (young sedentary) vs. 859 ± 49 (middle-aged and older sedentary) cm/s, P < 0.001] but was 20% lower in middle-aged and older trained (686 ± 30 cm/s) than in middle-aged and older sedentary (P < 0.005). Short-term (4 days x 2500–4500 mg) treatment with the NF&kgr;B inhibitor salsalate (randomized, placebo-controlled cross-over design) reduced aPWV (to 783 ± 44 cm/s, P < 0.05) without changing BP (P = 0.40) or heart rate (P = 0.90) in middle-aged and older sedentary, but had no effect in young sedentary (623 ± 19) or middle-aged and older trained (699 ± 30). Following salsalate treatment, aPWV no longer was significantly different in middle-aged and older sedentary vs. middle-aged and older trained (P = 0.29). The reduction in aPWV with salsalate administration was inversely related to baseline (placebo) aPWV (r = −0.60, P < 0.001). Conclusion: These results support the hypothesis that suppressed NF&kgr;B signalling may partially mediate the lower aortic stiffness in middle-aged and older adults who regularly perform aerobic exercise. Because aPWV predicts incident cardiovascular events in this population, this suggests that tonic suppression of NF&kgr;B signalling in middle-aged and older exercising adults may potentially lower cardiovascular risk.
A Study on Behavioral Backward Incompatibility Bugs in Java Software Libraries

Nowadays, due to the frequent technological innovationand market changes, software libraries are evolving veryquickly. To make sure that existing client software applicationsare not broken after a library update, backward compatibilityhas always been one of the most important requirements duringthe evolution of software platforms and libraries. However, due to various reasons, backward compatibility is seldom fullyachieved in practice, and many relevant software failures arereported. Therefore, it is important to understand the status, major reasons, and impact of backward incompatibilities in realworld software. Previous studies on this topic mainly focus onAPI signature changes between consecutive versions of softwarelibraries, but behavioral changes of APIs with untouched signaturesare actually more dangerous and are causing most realworldbugs because they cannot be easily detected. This paperpresents an empirical study on 126 real-world software bugreports on backward incompatibilities of software libraries. Wefind that 67% of fixed client bugs caused by backward incompatibilitiesin software libraries are fixed by client developers, through several simple change patterns made to the backwardincompatible API invocations.
Procrastinating Behavior in Computer-Based Learning Environments to Predict Performance: A Case Study in Moodle

Introduction: Research about student performance has traditionally considered academic procrastination as a behavior that has negative effects on academic achievement. Although there is much evidence for this in class-based environments, there is a lack of research on Computer-Based Learning Environments (CBLEs). Therefore, the purpose of this study is to evaluate student behavior in a blended learning program and specifically procrastination behavior in relation to performance through Data Mining techniques. Materials and Methods: A sample of 140 undergraduate students participated in a blended learning experience implemented in a Moodle (Modular Object Oriented Developmental Learning Environment) Management System. Relevant interaction variables were selected for the study, taking into account student achievement and analyzing data by means of association rules, a mining technique. The association rules were arrived at and filtered through two selection criteria: 1, rules must have an accuracy over 0.8 and 2, they must be present in both sub-samples. Results: The findings of our study highlight the influence of time management in online learning environments, particularly on academic achievement, as there is an association between procrastination variables and student performance. Conclusion: Negative impact of procrastination in learning outcomes has been observed again but in virtual learning environments where practical implications, prevention of, and intervention in, are different from class-based learning. These aspects are discussed to help resolve student difficulties at various ages.
More unequal or less? A review of global, regional and national income inequality

This article presents a multi-perspective discussion of trends in income inequality. Recent evidence from many sources shows that global income inequality is high and relatively stable, with the main changes being driven by developments in China and India. In developed countries, the trend has been towards higher levels of inequality over the last thirty years; and this has also been true of developing countries in the past decade, with the exception of Latin America, which is analysed here in detail. In the region, income became less unevenly distributed between 2002 and 2014, mainly because inequality within countries declined in most cases; but the latest measurements suggest that this trend is faltering.
Review article: the association between nodular regenerative hyperplasia, inflammatory bowel disease and thiopurine therapy

Nodular regenerative hyperplasia (NRH) is increasingly being recognised in patients with inflammatory bowel disease (IBD). However, the pathogenesis and incidence of NRH in IBD, and the putative roles played by azathioprine (AZA), mercaptopurine (MP), or tioguanine (TG) remain unclear.
Influence of shell parameters on response of polymer-shelled microbubbles to high-frequency ultrasound

Polymer-shelled ultrasound contrast agents (UCAs) can undergo a “compression only” behavior leading to shell rupture and nonlinear response of the released gas bubbles when ultrasonically excited below 10 MHz. This study investigated if polymer-shelled UCAs exhibited a similar behavior when excited at frequencies above 10 MHz. Accordingly, two experiments were performed: one examined the compression-induced rupture of UCA shells by subjecting them to static overpressure, and the other investigated subharmonic components in the backscattered signal produced by individual UCAs sonicated with 20-MHz tonebursts. Four varieties of polylactide-shelled UCAs, each with a distinct shell-thickness-to-radius ratio (STRR), were employed; the STRRs were 7.5, 40, 65, and 100 nm/μm. Different UCA types exhibited distinctly different rupture thresholds that were linearly related to their STRR, but uncorrelated with UCA size. The subharmonic response of these polymer-shelled UCAs did not exhibit a strong correlation with UCA-rupture pressures and, consequently, their STRRs. Although the Philips UCAs had greater STRRs in comparison to Point UCAs and were more resilient, they produced significantly greater subharmonic activity than the Point UCAs. The results of this two-part study indicated that the polymer-shelled UCAs may not adhere to the rupture-based mechanism of subharmonic generation when excited at 20 MHz.
Loss of secretory response of rat basophilic leukemia (2H3) cells at 40 degrees C is associated with reversible suppression of inositol phospholipid breakdown and calcium signals.

Antigen-induced stimulatory signals as well as histamine secretion from the RBL-2H3 cells were found to be highly temperature dependent. There was no hydrolysis of inositol phospholipids, increase in cytosol calcium concentration (calcium signal), or secretion upon antigen stimulation at temperatures below 20 degrees C. At higher temperatures (i.e., 20 to 37 degrees C), all responses increased in extent with increase in temperature. Temperatures of 38 degrees C or higher, however, resulted in a marked decline in all responses, until no responses were observed at 40 to 42 degrees C. As indicated by the decay in calcium signal, the duration of response was also temperature dependent. The response was of long duration at 30 to 32 degrees C, but it became progressively more transient as the temperature was increased from 32 to 40 degrees C. The effects of low or high temperature were fully reversible. For example, in the presence of antigen, stimulatory signals immediately appeared once the temperature was decreased from 40 to 37 degrees C. Although the diminished responses could be explained, in part, by a reduction in rates of IgE receptor aggregation and phospholipase C activity, the reductions were insufficient to account for complete loss of activity at 40 degrees C. We conclude that generation of intracellular signals in 2H3 cells is blocked by quite small elevations in temperature above 37 degrees C, possibly as consequence of changes in membrane fluidity.
Generative mathematical modelling to demonstrate virtual simulations of neovascular age related macular degeneration

Purpose To develop a generative mathematical model of wet age-related macular degeneration (AMD) and model the impact of injections of anti-vascular endothelial growth factor to virtual patients with the condition. Methods We isolated key pathophysiological components of macular degeneration in terms of macular edema development and response to anti-vascular endothelial growth factor (VEGF) agents. We developed mathematical models for each of these components using constants determined from published biological experimentation. Consequently, we combined the mathematical models of the separate components to arrive at an end-to-end model of the evolution of macular edema size and its response to treatment. Results We present a series of simulations based upon our idealised model. Initially, we demonstrate the theoretical change in macular edema height in wet macular degeneration over time without and with anti-VEGF interventions. In our final simulation, we demonstrate the powerful possibilities of virtual clinical trials by simulating a virtual model of a landmark study using our existing mathematical AMD model. Conclusions Using our mathematical modelling based upon known pathological and pharmacological processes we have been able to model the effect of intravitreal injection of an anti-VEGF agent on macular edema from age related macular degeneration. We were subsequently able to mathematically simulate a major clinical trial with results that mirror many key features of the clinical established study. We anticipate that the generative model presented here can evolve to be a useful supportive tool in the challenge to deliver optimal therapy for patients with wet macular degeneration.
Performance et défense de l’unité familiale : la valeur du capital émotionnel

L’unité, un particularisme de l’entreprise familiale, nous intéresse pour la logique émotionnelle qu’elle recèle. Dans un but de compréhension de la valeur en contexte familial, nous étudions un phénomène complexe, celui du risque de rupture de l’intégrité d'un groupe. L’entrisme de LVMH au capital d’Hermès a eu pour conséquence un renforcement de la défense de l’unité familiale d’Hermès. La menace d’une prise de contrôle rampante a élevé l’unité au rang de priorité. Sa préservation détruit certes de la valeur financière mais pérennise le modèle et met en évidence l'impact de la valeur socio-émotionnelle.
A comparison of learning rules in pulse-based neural networks

With a similar mechanism of processing spikes as biological neural systems, spiking neural networks (SNNs) are expected to perform a better performance than traditional rate based neural networks. Despite the progress in the application of SNNs, how does the brain learn information from spiking based codes remains an open question. To train a spiking neuron output desired spike trains, many learning methods have been proposed, and can be mainly divided into two classes: spike-driven methods and membrane potential-driven methods. Moreover, different learning algorithms have different advantages in different applications. Therefore, in this paper, we analysis and compare the existing learning algorithm for spiking neurons, including learning efficiency, learning accuracy.
Expression and Localization of Human Endothelin-Converting Enzyme-1 Isoforms in Symptomatic Atherosclerotic Disease and Saphenous Vein

Endothelin-converting enzyme (ECE-1) is a critical enzyme in the production of the potent vasoconstrictor peptide endothelin (ET-1). It has previously been shown that the levels of both ET-1 and ECE-1 are raised in atherosclerosis, but the possible relevance of the isoforms of ECE-1 in these changes has not yet been investigated. The aim of this study was to examine the expression of the ECE-1a and ECE-1c isoforms in human atherosclerotic pathologies. Immunohistochemical analysis was carried out on sections from atherosclerotic and non-atherosclerotic vascular tissue using a combination of ECE-1 isoform-specific antibodies, anti–α-actin antibodies to identify smooth muscle cells (SMC) and anti-CD68 antibodies to identify macrophages. ECE-1 isoform expression was also examined in cultured SMC and in macrophages isolated from human blood. Results indicated differences in isoform expression in athero-sclerotic lesions, with distinct patterns of staining for ECE-1a and ECE-1c. ECE-1c immunoreactivity was seen in macrophages, and also correlated with actin staining. ECE-1a was also localized to macrophages and SMC. Results of this study suggest that these local changes influence the expression patterns of the ECE-1 isoforms within individual cell types. Correlation of these isoform expression patterns with the stage of atherosclerosis could provide novel indicators of disease progression.
Attributable cost of catheter-associated bloodstream infections among intensive care patients in a nonteaching hospital*

Objective:To determine the attributable cost and length of stay of intensive care unit (ICU)–acquired, catheter-associated bloodstream infections from a hospital-based cost perspective, after adjusting for potential confounders. Design:Patients admitted to the ICU between January 19, 1998, and July 31, 2000, were observed prospectively for the occurrence of catheter-associated bloodstream infections. Hospital costs were obtained from the hospital cost accounting database. Setting:The medical and surgical ICUs at a 500-bed suburban, tertiary care hospital. Patients:Patients requiring central venous catheterization while in the ICU. Interventions:None. Measurements and Main Results:We measured occurrence of catheter-associated bloodstream infection, in-hospital mortality rate, total ICU and hospital lengths of stay, and total hospital costs. Catheter-associated bloodstream infection occurred in 41 of 1,132 patients (3.6 cases per 1000 catheter days). Patients with catheter-associated bloodstream infection had significantly higher unadjusted ICU length of stay (median, 24 vs. 5 days; p < .001), hospital length of stay (median, 45 vs. 11 days; p < .001), mortality rate (21 [51%] vs. 301 [28%], p = .001), and total hospital costs ($83,544 vs. $23,803, p < .001). Controlling for other factors that may affect costs and lengths of stay, catheter-associated bloodstream infections resulted in an attributable cost of $11,971 (95% confidence interval, $6,732–$18,352), ICU length of stay of 2.41 days (95% confidence interval, 0.08–3.09 days), and hospital length of stay of 7.54 days (95% confidence interval, 3.99–11.09 days). Conclusions:Patients with catheter-associated bloodstream infection had significantly longer ICU and hospital lengths of stay, with higher unadjusted total mortality rate and hospital cost compared with uninfected patients. After adjusting for underlying severity of illness, the attributable cost of catheter-associated bloodstream infection was approximately $11,971.