Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell Culture Models for the Investigation of Hepatitis B and D Virus Infection

Chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) infections are major causes of liver disease and hepatocellular carcinoma worldwide. Despite the presence of an efficient preventive vaccine, more than 250 million patients are chronically infected with HBV. Current antivirals effectively control but only rarely cure chronic infection. While the molecular biology of the two viruses has been characterized in great detail, the absence of robust cell culture models for HBV and/or HDV infection has limited the investigation of virus-host interactions. Native hepatoma cell lines do not allow viral infection, and the culture of primary hepatocytes, the natural host cell for the viruses, implies a series of constraints restricting the possibilities of analyzing virus-host interactions. Recently, the discovery of the sodium taurocholate co-transporting polypeptide (NTCP) as a key HBV/HDV cell entry factor has opened the door to a new era of investigation, as NTCP-overexpressing hepatoma cells acquire susceptibility to HBV and HDV infections. In this review, we summarize the major cell culture models for HBV and HDV infection, discuss their advantages and limitations and highlight perspectives for future developments.
New supergravity backgrounds dual to = 1 SQCD-like theories with Nf = 2Nc

We present new supergravity backgrounds generated by Nc D5-branes, wrapping the S2 of the resolved conifold, in the presence of Nf = 2Nc smeared flavor D5-branes. The smearing allows us to take into account their backreaction on the geometry. We discuss the consistency, stability, and supersymmetry of these types of setups. We find near horizon geometries that we expect to be supergravity duals of SQCD-like theories with Nf = 2Nc. From these backgrounds, we numerically extract rectangular Wilson loops and beta functions of the dual field theory for the regime where our approximations are valid.
Balance of payment crises in emerging markets: how early were the ‘early’ warning signals?

Although many papers have already proposed empirical models of currency crises, the timing of such crises has received relatively little attention so far. Most papers use indeed a static specification and impose the same lag structure across all explanatory variables. This, by construction, prevents from specifically timing the crisis signals sent by the leading indicators. The objective here is to fill this gap by considering a set of dynamic discrete choice models. The first contribution is to identify how early in advance each explanatory variable sends a warning signal. Some indicators are found to signal a crisis in the very short run while others signal a crisis at more distant horizons. The second contribution is to show that state dependence matters, albeit mostly in the short run. The results have important implications for crisis prevention in terms of the timeliness and usefulness of the envisaged policy response.
On-Line Transition-Time Monitoring for Die-to-Die Interconnects in 3D ICs

Through Silicon Vias (TSVs) are known to be susceptible to various thermal-mechanical and electro-migration effects that could lead to unexpected resistance increase after certain time of field operation. To cope with this reliability threat, we present an on-line monitoring method that aims to continuously detect excessive transition time occurring to a TSV (which often indicates performance degradation). Our method attaches a monitor to the termination end of a TSV. Any transition there is converted into a pulse-width, which is further compared to a dynamically tunable threshold. A Timing Failure Threat (TFT) is thereby detected when the pulse-width exceeds the threshold. This method can be applied to a large number of TSVs easily since the monitoring results are binary and can be stored in FFs forming a scan chain for easy access.
The year in cardiology: heart failure 2014.

The year 2014 has become a remarkable year for heart failure. A bad start was caused by the publication of TOPCAT, showing that spironolactone did not prove to be beneficial for the treatment of patients with heart failure and preserved ejection fraction (HFpEF). Nevertheless, further insights in the study yields a few bright spots, and treatment with spironolactone might still be considered in patients with HFpEF. In acute heart failure, additional data were published on the effects of serelaxin. Serelaxin reduced wedge pressures, had similar effects in acute heart failure patients with and without a reduced ejection fraction, and had a neutral effect on diuretic response. But the most important news was related to the results of PARADIGM, where LCZ696, the first-in-class angiotensin-receptor neprilysin inhibitor, proved to be superior to enalapril in reducing mortality and morbidity in patients with heart failure and reduced ejection fraction (HFrEF). During the last decades, treatment of patients with heart failure with reduced ejection fraction (HFrEF) has improved dramatically with the introduction of ACE-inhibitors, β-blockers, angiotensin receptor blockers, and mineralocorticoid receptor antagonists. This caused a stepwise reduction in mortality and heart failure hospitalization. However, residual mortality and morbidity is still too high. Therefore, there is a continuous need for better therapies. The biggest heart failure news of 2014 in heart failure was the presentation and publication of the PARADIGM trial.1 The trial reported the effects of LCZ696, a first in class angiotensin receptor neprilysin inhibitor. LCZ696 comprises the molecular moieties of the angiotensin II AT1 receptor antagonist valsartan and the neprilysin inhibitor prodrug AHU377.2 In PARADIGM, the effect of LCZ696 on a composite of death from cardiovascular causes …
Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats

The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280–350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50–60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation.
Dwarf galaxies in voids: suppressing star formation with photoheating

We study the structure formation in cosmological void regions using high-resolution hydrody-namical simulations. Despite being significantly underdense, voids are populated abundantly with small dark matter haloes which should appear as dwarf galaxies if their star formation is not suppressed significantly. We here investigate to which extent the cosmological ultraviolet (UV) background reduces the baryon content of dwarf galaxies, and thereby limits their cooling and star formation rates. Assuming a Haardt & Madau UV background with reionization at redshift z = 6, our samples of simulated galaxies show that haloes with masses below a characteristic mass of M c (z = 0) = 6.5 x 10 9 h -1 M ⊙ are baryon-poor, but in general not completely empty, because baryons that are in the condensed cold phase or are already locked up in stars resist evaporation. In haloes with mass M? M c , we find that photoheating suppresses further cooling of gas. The redshift- and UV-background-dependent characteristic mass M c (z) can be understood from the equilibrium temperature between heating and cooling at a characteristic overdensity of δ ≃ 1000. If a halo is massive enough to compress gas to this density despite the presence of UV-background radiation, gas is free to 'enter' the condensed phase and cooling continues in the halo, otherwise it stalls. By analysing the mass accretion histories of dwarf galaxies in voids, we show that they can build up a significant amount of condensed mass at early times before the epoch of reionization. Later on, the amount of mass in this phase remains roughly constant, but the masses of the dark matter haloes continue to increase. Consequently, photoheating leads to a reduced baryon fraction in void dwarf galaxies, endows them with a rather old stellar population, but still allows late star formation to some extent. We estimate the resulting stellar mass function for void galaxies. While the number of galaxies at the faint end is significantly reduced due to photoheating, additional physical feedback processes may be required to explain the apparent paucity of dwarfs in observations of voids.
DksA-Dependent Transcriptional Regulation in Salmonella Experiencing Nitrosative Stress

Redox-based signaling is fundamental to the capacity of bacteria to sense, and respond to, nitrosative and oxidative stress encountered in natural and host environments. The conserved RNA polymerase regulatory protein DksA is a thiol-based sensor of reactive nitrogen and oxygen species. DksA-dependent transcriptional control promotes antinitrosative and antioxidative defenses that contribute to Salmonella pathogenesis. The specific adaptive changes mediated by DksA in response to reactive species, however, have not been elucidated. Herein, we characterize DksA-dependent changes in gene expression in Salmonella enterica experiencing nitrosative stress. Genome-wide expression analysis of wild-type and ΔdksA Salmonella exposed to the nitric oxide (•NO) donor DETA NONOate demonstrated •NO- and DksA-dependent regulatory control of 427 target genes. Transcriptional changes centered primarily on genes encoding aspects of cellular metabolism. Several antioxidants and oxidoreductases important in redox buffering, •NO detoxification, and damage repair were also observed to be up-regulated in an •NO- and DksA-dependent manner. Compared to wild-type bacteria, •NO-treated ΔdksA Salmonella exhibited a de-repression of genes encoding components of iron homeostasis and failed to activate sulfur assimilation and cysteine biosynthetic operons. As cysteine is integral to efficient antinitrosative and antioxidative defense and repair programs, we further examined the redox-responsive transcriptional control of cysteine biosynthesis by DksA. These investigations revealed that the activation of genes comprising cysteine biosynthesis also occurs in response to hydrogen peroxide, is dependent upon the redox-sensing zinc finger motif of DksA, and requires the transcriptional regulator CysB. Our observations demonstrate that DksA mediates global adaptation to nitrosative stress in Salmonella and provide unique insight into a novel regulatory mechanism by which cysteine biosynthesis is controlled in response to reactive oxygen and nitrogen species.
The Correlation Between Small Dense LDL and Reactive Oxygen Metabolites in a Physical Activity Intervention in Hyperlipidemic Subjects

Background Small dense low-density lipoprotein (sdLDL), which has a small LDL particle size with a greater susceptibility to oxidation, is considered a risk marker for cardiovascular disease (CVD). The diacron reactive oxygen metabolites (d-ROMs) have recently been introduced as a clinically useful oxidative stress-related marker. Physical activity can reduce the CVD risk. The present study investigated the correlation between the changes of the mean LDL particle size and the oxidative stress status, as assessed by the d-ROMs, in a physical activity intervention in hyperlipidemic subjects. Methods We performed a 6-month intervention study of 30 hyperlipidemic subjects (12 male/18 female, mean age 64 years), focusing on a moderate physical activity increase. The clinical data, including the atherosclerotic risk factors besides the mean LDL particle size measured with the gel electrophoresis and the d-ROMs, were evaluated pre- and post-intervention. Results The mean LDL particle size was significantly larger in the post-intervention than in the pre-intervention evaluation (26.9 ± 0.3 (SD) vs. 27.1 ± 0.4 nm, P < 0.01), while the d-ROMs levels were significantly reduced in the post-intervention period compared to those at pre-intervention (319 ± 77 vs. 290 ± 73 U. Carr., P < 0.05). A stepwise multiple regression analysis revealed that there was an independent, significant and inverse correlation between the pre- and post-intervention changes of the d-ROMs and the mean LDL particle size (β = -0.55, P < 0.01). Conclusions The intervention study suggests that sdLDL and oxidative stress can concomitantly affect the risk of developing CVD and that both factors can improve by even a moderate increase in physical activity among hyperlipidemic subjects.
Algebra-Based Scalable Overlay Network Monitoring: Algorithms, Evaluation, and Applications

Overlay network monitoring enables distributed Internet applications to detect and recover from path outages and periods of degraded performance within seconds. For an overlay network with end hosts, existing systems either require measurements, and thus lack scalability, or can only estimate the latency but not congestion or failures. Our earlier extended abstract [Y. Chen, D. Bindel, and R. H. Katz, ldquoTomography-based overlay network monitoring,rdquo Proceedings of the ACM SIGCOMM Internet Measurement Conference (IMC), 2003] briefly proposes an algebraic approach that selectively monitors linearly independent paths that can fully describe all the paths. The loss rates and latency of these paths can be used to estimate the loss rates and latency of all other paths. Our scheme only assumes knowledge of the underlying IP topology, with links dynamically varying between lossy and normal. In this paper, we improve, implement, and extensively evaluate such a monitoring system. We further make the following contributions: i) scalability analysis indicating that for reasonably large n (e.g., 100), the growth of k is bounded as O(n log n), ii) efficient adaptation algorithms for topology changes, such as the addition or removal of end hosts and routing changes, iii) measurement load balancing schemes, iv) topology measurement error handling, and v) design and implementation of an adaptive streaming media system as a representative application. Both simulation and Internet experiments demonstrate we obtain highly accurate path loss rate estimation while adapting to topology changes within seconds and handling topology errors.
Efficacy and Safety of Flibanserin for the Treatment of Hypoactive Sexual Desire Disorder in Women: A Systematic Review and Meta-analysis.

IMPORTANCE In August 2015, the US Food and Drug Administration (FDA) approved flibanserin as a treatment for hypoactive sexual desire disorder (HSDD) in premenopausal women, despite concern about suboptimal risk-benefit trade-offs. OBJECTIVE To conduct a systematic review and meta-analysis of randomized clinical trials assessing efficacy and safety of flibanserin for the treatment of HSDD in women. DATA SOURCES Medical databases (among others, Embase, Medline, Psycinfo) and trial registries were searched from inception to June 17, 2015. Reference lists of retrieved studies were searched for additional publications. STUDY SELECTION Randomized clinical trials assessing treatment effects of flibanserin in premenopausal and postmenopausal women were eligible. No age, language, or date restrictions were applied. Abstract and full-text selection was done by 2 independent reviewers. DATA EXTRACTION AND SYNTHESIS Data were extracted by one reviewer and checked by a second reviewer. Results were pooled using 2 approaches depending on the blinding risk of bias. MAIN OUTCOMES AND MEASURES Primary efficacy outcomes included number of satisfying sexual events (SSEs), eDiary sexual desire, and Female Sexual Function Index (FSFI) desire. Safety outcomes included, among others, 4 common adverse events (AEs): dizziness, somnolence, nausea, and fatigue. RESULTS Five published and 3 unpublished studies including 5914 women were included. Pooled mean differences for SSE change from baseline were 0.49 (95% CI, 0.32-0.67) between 100-mg flibanserin and placebo, 1.63 (95% CI, 0.45-2.82) for eDiary desire, and 0.27 (95% CI, 0.17-0.38) for FSFI desire. The risk ratio for study discontinuation due to AEs was 2.19 (95% CI, 1.50-3.20). The risk ratio for dizziness was 4.00 (95% CI, 2.56-6.27) in flibanserin vs placebo, 3.97 (95% CI, 3.01-5.24) for somnolence, 2.35 (95% CI, 1.85-2.98) for nausea, and 1.64 (95% CI, 1.27-2.13) for fatigue. Women's mean global impression of improvement scores indicated minimal improvement to no change. CONCLUSIONS AND RELEVANCE Treatment with flibanserin, on average, resulted in one-half additional SSE per month while statistically and clinically significantly increasing the risk of dizziness, somnolence, nausea, and fatigue. Overall, the quality of the evidence was graded as very low. Before flibanserin can be recommended in guidelines and clinical practice, future studies should include women from diverse populations, particularly women with comorbidities, medication use, and surgical menopause.
Permanent supportive housing for domestic violence victims: program theory and client perspectives

The US Violence Against Women Act of 2005 allocated $10 million to support collaborative efforts to create permanent housing options for domestic violence victims. Such programs are relatively new and rare, and up to now little research has examined their efficacy. This research investigates one permanent housing option, the permanent supportive housing model, through an exploratory case study of a Connecticut-based program currently being developed. The study compares the program design articulated by administrators and advocates with perspectives of domestic violence agency clients. Findings indicate important differences between the program activities and goals articulated by administrators, and those preferred by clients. Although everyone agreed that personal safety was a priority, administrators stressed independence and choice whereas clients sought a stricter, community-centered environment with time-limited stays. These themes can be used to develop hypotheses for larger studies and have important preliminary policy and program implications.
Dispersal Can Limit Local Plant Distribution

The ability of species to establish new popuiations at unoccupied sites is a critical feature in the maintenance of biological diversity, and it has taken on new importance as a result of global climate change and expected changes in species distributior~ To examine the dispersal potential of plant specie~ seeds of four annual piant species were exper- imentally dispersed 40 to 600 m from existing populations in Massachusetts (U.Xik ) to 34 nearby unoccupied but ap- parently suitable siteg At three of these site~ new popula- tions were established that persisted for four generations and expanded slowly in area At seven site~ a small tnttial pop- uiation eventually died out At the 24 other siteg new pop- ulatiom did not become established, indicating that the sites were in some way unsuitabl¢ that not enough seeds arrived, or that conditions suitable for seed germination do not oc- cur every year. These results suggest that some species may be unable to disperse naturally out of their existing ranges in response to global climate changg particularly if habitat fragmentation creates barriers to dispersal These species may have to be assisted to reach suitable sites nearby to prevent their extinction in the wild.
Book Review: Neural Connections and Receptive Field Properties in the Primary Visual Cortex

A cubic millimeter of primary visual cortex contains about 100,000 neurons that are heavily interconnected by intrinsic and extrinsic afferents. The effort of many neuroanatomists over the past has revealed the general outline of these connections; however, their function remains a mystery. Recently, combined physiological and anatomical approaches are beginning to reveal the role of these connections in the generation of cortical receptive fields. A common theme emerges from all these studies: cortical connections are remarkably specific and this specificity is determined in great extent by the type of connection and the neuronal response properties. Feedforward connections follow relatively rigid rules of wiring selectively targeting neurons with receptive fields matched in position and contrast polarity (thalamus—cortical layer 4) or position and orientation selectivity (layer 4—layers 2 + 3). In contrast, horizontal connections follow more flexible rules connecting distant cells that are not retinotopically aligned and neighboring cells with different orientation preferences. These differences in connectivity may give a hint on how visual stimuli are processed in the primary visual cortex. An attractive hypothesis is that local stimuli use the highly selective feedforward inputs to reliably drive cortical neurons while background stimuli modulate their activity through more flexible horizontal (and feedback) connections.
CD4+ T-Cell Effectors Inhibit Epstein-Barr Virus-Induced B-Cell Proliferation

ABSTRACT In immunodeficient hosts, Epstein-Barr virus (EBV) often induces extensive B-cell lymphoproliferative disease and lymphoma. Without effective in vitro immune surveillance, B cells infected by the virus readily form immortalized cell lines. In the regression assay, memory T cells inhibit the formation of foci of EBV-transformed B cells that follows recent in vitro infection by EBV. No one has yet addressed which T cell regulates the early proliferative phase of B cells newly infected by EBV. Using new quantitative methods, we analyzed T-cell surveillance of EBV-mediated B-cell proliferation. We found that CD4+ T cells play a significant role in limiting proliferation of newly infected, activated CD23+ B cells. In the absence of T cells, EBV-infected CD23+ B cells divided rapidly during the first 3 weeks after infection. Removal of CD4+ but not CD8+ T cells also abrogated immune control. Purified CD4+ T cells eliminated outgrowth when added to EBV-infected B cells. Thus, unlike the killing of EBV-infected lymphoblastoid cell lines, in which CD8+ cytolytic T cells play an essential role, prevention of early-phase EBV-induced B-cell proliferation requires CD4+ effector T cells.