Miracle-dz/UniFAR-FTUs huggingface dataset:
Correlation of Noncancer Benchmark Doses in Short‐ and Long‐Term Rodent Bioassays

This study investigated whether, in the absence of chronic noncancer toxicity data, short‐term noncancer toxicity data can be used to predict chronic toxicity effect levels by focusing on the dose–response relationship instead of a critical effect. Data from National Toxicology Program (NTP) technical reports have been extracted and modeled using the Environmental Protection Agency's Benchmark Dose Software. Best‐fit, minimum benchmark dose (BMD), and benchmark dose lower limits (BMDLs) have been modeled for all NTP pathologist identified significant nonneoplastic lesions, final mean body weight, and mean organ weight of 41 chemicals tested by NTP between 2000 and 2012. Models were then developed at the chemical level using orthogonal regression techniques to predict chronic (two years) noncancer health effect levels using the results of the short‐term (three months) toxicity data. The findings indicate that short‐term animal studies may reasonably provide a quantitative estimate of a chronic BMD or BMDL. This can allow for faster development of human health toxicity values for risk assessment for chemicals that lack chronic toxicity data.
Impact of Digital Labeling on Outcome Measures

Objective The purpose of this study was to determine whether the label attached to the hearing aid being presented would bias outcome measures towards newer technological designs. Design Two groups of subjects participated in this investigation. The groups were matched for age, gender, previous hearing aid experience, degree and configuration of hearing loss. Group A wore each of two digital hearing aids for 1 mo; Group B wore the same digital hearing aid for 2 mo, but the subjects were given the impression they were changing hearing aids after 1 mo. In each group the subjects were told that one of the months they were wearing a “digital” hearing aid and one of the months they were wearing a “conventional” hearing aid. Outcome measures consisted of a number of behavioral speech perception tasks and self-report measures, each completed at the onset and after 1 mo use with the hearing aids. Results Labeling effects were observed for many of the outcome measures. Using a mixed-model factorial analysis of variance to control for irrelevant variables and to explore interaction terms, prejudice (digital versus conventional labeling) was treated as a within-subject factor while the subject group (A or B) and clinician were treated as between-subject factors. Although only the APHAB RV and BN scales showed significant labeling effects on their own, the group of tests used in this study showed a significant labeling effect as a whole (p < 0.01). The total influence of labeling and related interaction terms indicated labeling-related effects accounted for 2 to 32% of the variance in individual outcome measures. Discussion The results of this investigation indicate a need for double-blinding in hearing aid research aimed at assessing the effectiveness of newer technologies, as well as a need for clinicians to critically evaluate the research describing the potential advantages of certain circuit options.
Responding to a changing nation: are faculty prepared for cross-cultural conversations and care?

BACKGROUND AND OBJECTIVES The United States is becoming increasingly diverse. Health disparities continue with little improvement despite national policies and standards. Medical institutions are modifying their curricula; however, little is known about faculty attitudes and comfort in addressing cultural issues. The purpose of this study was to determine faculty attitudes, self-perceived levels of comfort and skill, and future knowledge needs pertaining to cultural competence. METHODS A survey was administered to all clinical faculty at the University of Virginia School of Medicine. Survey questions addressed faculty attitudes and self-perceived levels of comfort and skill in dealing with cultural issues, as well as perceived need and interest in future cultural competence training. RESULTS When considering each phase of education (medical school, residency, continuing medical education [CME]), fewer than 25% of the respondents reported receiving formal instruction in cultural competency in any given phase, although 93% felt that cultural competency training was important. Fifty-eight percent felt "very comfortable" caring for diverse patients, although this dropped to 30% when specifying limited English proficiency. The situation in which the highest percentage of respondents felt "not particularly comfortable" or "not at all comfortable" was breaking bad news to a patient's family first if this was more culturally appropriate (47%). Respondents felt most skilled in working with medical interpreters, apologizing for cross-cultural misunderstandings, and eliciting the patients' perspectives about their health and illness. Respondents felt the least skilled providing culturally sensitive end-of-life care and dealing with cross-cultural conflicts. CONCLUSIONS Clinical faculty have received limited instruction on cultural competency, and the reported levels of comfort and skill in many challenging areas of multicultural health leave much room for improvement. Until faculty become more comfortable and are able to model and teach these behaviors to learners, positive responses to national policies in culturally competent care are likely to be limited.
Cardioprotective Angiotensin-(1–7) Peptide Acts as a Natural-Biased Ligand at the Angiotensin II Type 1 Receptor

Hyperactivity of the renin–angiotensin–aldosterone system through the angiotensin II (Ang II)/Ang II type 1 receptor (AT1-R) axis constitutes a hallmark of hypertension. Recent findings indicate that only a subset of AT1-R signaling pathways is cardiodeleterious, and their selective inhibition by biased ligands promotes therapeutic benefit. To date, only synthetic biased ligands have been described, and whether natural renin–angiotensin–aldosterone system peptides exhibit functional selectivity at AT1-R remains unknown. In this study, we systematically determined efficacy and potency of Ang II, Ang III, Ang IV, and Ang-(1–7) in AT1-R–expressing HEK293T cells on the activation of cardiodeleterious G-proteins and cardioprotective &bgr;-arrestin2. Ang III and Ang IV fully activate similar G-proteins than Ang II, the prototypical AT1-R agonist, despite weaker potency of Ang IV. Interestingly, Ang-(1–7) that binds AT1-R fails to promote G-protein activation but behaves as a competitive antagonist for Ang II/Gi and Ang II/Gq pathways. Conversely, all renin–angiotensin–aldosterone system peptides act as agonists on the AT1-R/&bgr;-arrestin2 axis but display biased activities relative to Ang II as indicated by their differences in potency and AT1-R/&bgr;-arrestin2 intracellular routing. Importantly, we reveal Ang-(1–7) a known Mas receptor-specific ligand, as an AT1-R–biased agonist, selectively promoting &bgr;-arrestin activation while blocking the detrimental Ang II/AT1-R/Gq axis. This original pharmacological profile of Ang-(1–7) at AT1-R, similar to that of synthetic AT1-R–biased agonists, could, in part, contribute to its cardiovascular benefits. Accordingly, in vivo, Ang-(1–7) counteracts the phenylephrine-induced aorta contraction, which was blunted in AT1-R knockout mice. Collectively, these data suggest that Ang-(1–7) natural-biased agonism at AT1-R could fine-tune the physiology of the renin–angiotensin–aldosterone system.
Neural differentiation and synaptogenesis in retinal development

To investigate the pattern of neural differentiation and synaptogenesis in the mouse retina, immunolabeling, BrdU assay and transmission electron microscopy were used. We show that the neuroblastic cell layer is the germinal zone for neural differentiation and retinal lamination. Ganglion cells differentiated initially at embryonic day 13 (E13), and at E18 horizontal cells appeared in the neuroblastic cell layer. Neural stem cells in the outer neuroblastic cell layer differentiated into photoreceptor cells as early as postnatal day 0 (P0), and neural stem cells in the inner neuroblastic cell layer differentiated into bipolar cells at P7. Synapses in the retina were mainly located in the outer and inner plexiform layers. At P7, synaptophysin immunostaining appeared in presynaptic terminals in the outer and inner plexiform layers with button-like structures. After P14, presynaptic buttons were concentrated in outer and inner plexiform layers with strong staining. These data indicate that neural differentiation and synaptogenesis in the retina play important roles in the formation of retinal neural circuitry. Our study showed that the period before P14, especially between P0 and P14, represents a critical period during retinal development. Mouse eye opening occurs during that period, suggesting that cell differentiation and synaptic formation lead to the attainment of visual function.
Impact of intensive care unit discharge time on patient outcome

Objective:To determine the impact of nighttime intensive care unit (ICU) discharge on patient outcome. Design:Multiple-center, retrospective observational cohort study. Setting:Canadian hospitals. Patients:We used a prospectively collected dataset containing information on 79,090 consecutive admissions from 31 Canadian community and teaching hospitals. Interventions:None. Measurements and Main Results:Patients were categorized according to the time of ICU discharge into daytime (07:00–20:59) and nighttime (21:00–06:59). Admissions were excluded if the patients were a) ≤16 yrs of age (392); b) admitted following cardiac surgery (6,641); c) admitted following the initial admission for patients readmitted to the ICU within the same hospital stay (3,632); d) admitted due to a lack of available ward or specialty care beds (457); or c) transferred to another acute care facility (7,724). We found that 62,056 patients were discharged to the ward following the initial ICU admission. Of the 47,062 discharges eligible for analyses, 10.1% were discharged at night. The unadjusted odds of death for patients discharged from ICU at night was 1.35 (95% confidence interval, 1.23, 1.49), compared with patients discharged during the daytime. After adjustment for illness severity, source, case-mix, age, gender, and hospital size, the mortality risk was increased by 1.22-fold (95% confidence interval, 1.10, 1.36) for nighttime discharges. Multivariate regression analysis revealed that patients discharged from the ICU at night have a significantly shorter ICU length of stay than those discharged during the day (p < .001). Whereas hospital length of stay was similar for daytime and nighttime discharges who survived hospital stay, patients discharged at night who did not survive hospital stay had a significantly shorter hospital length of stay (p = .002). Conclusions:Patients discharged from the ICU at night have an increased risk of mortality compared with those discharged during the day.
Quality of sexual life of women on oral contraceptive continued-regimen: pilot study.

INTRODUCTION To date, women may use flexible oral contraceptive (OC) regimens. AIM The aim of this study was to evaluate the quality of sexual life of healthy women on continued-regimen OCs. METHODS Fifty women (age range 18-38) were enrolled. The Female Sexual Function Index (FSFI) and the Short Form-36 (SF-36) questionnaires were used to investigate, respectively, sexual behavior and the quality of life (QoL) of women on OC for 72 days with a 4-day hormone-free interval, for two cycles. Both the FSFI and the SF-36 were administered before starting OC intake, at the first (72-82 days) and the second (144-154 days) follow-ups. MAIN OUTCOME MEASURE The main outcomes are the FSFI and the SF-36 questionnaires. RESULTS The FSFI score obtained at the first follow-up detected a worsening with respect to baseline score (P < 0.05). The score obtained at the second follow-up detected an improvement with respect to both the baseline and the first follow-up total scores (P < 0.05). QoL improved at the first follow-up only as regards body pain (P < 0.05), and at the second follow-up as regards: physical role, body pain, general health, vitality, and social function (P < 0.05). CONCLUSIONS The use of continued-regimen OCs is able to improve the sexual behavior and the QoL of women.
HexA is a versatile regulator involved in the control of phenotypic heterogeneity of Photorhabdus luminescens

Phenotypic heterogeneity in microbial communities enables genetically identical organisms to behave differently even under the same environmental conditions. Photorhabdus luminescens, a bioluminescent Gram-negative bacterium, contains a complex life cycle, which involves a symbiotic interaction with nematodes as well as a pathogenic association with insect larvae. P. luminescens exists in two distinct phenotypic cell types, designated as the primary (1°) and secondary (2°) cells. The 1° cells are bioluminescent, pigmented and can support nematode growth and development. Individual 1° cells undergo phenotypic switching after prolonged cultivation and convert to 2° cells, which lack the 1° specific phenotypes. The LysR-type regulator HexA has been described as major regulator of this switching process. Here we show that HexA controls phenotypic heterogeneity in a versatile way, directly and indirectly. Expression of hexA is enhanced in 2° cells, and the corresponding regulator inhibits 1° specific traits in 2° cells. HexA does not directly affect bioluminescence, a predominant 1° specific phenotype. Since the respective luxCDABE operon is repressed at the post-transcriptional level and transcriptional levels of the RNA chaperone gene hfq are also enhanced in 2° cells, small regulatory RNAs are presumably involved that are under control of HexA. Another phenotypic trait that is specific for 1° cells is quorum sensing mediated cell clumping. The corresponding pcfABCDEF operon could be identified as the first direct target of HexA, since the regulator binds to the pcfA promoter region and thereby blocks expression of the target operon. In summary, our data show that HexA fulfills the task as repressor of 1° specific features in 2° cells in a versatile way and gives first insights into the complexity of regulating phenotypic heterogeneity in Photorhabdus bacteria.
Aspects of in vitro and in vivo research approaches directed toward identifying probiotics and prebiotics for human use.

The microbiota of the human gastrointestinal tract plays a key role in nutrition and health. Through the process of fermentation, gut bacteria metabolize various substrates (principally dietary components) to end products such as short-chain fatty acids and gases. This anaerobic metabolism is thought to contribute positively toward host daily energy requirements. However, under certain circumstances, the fermentative process may produce undesirable metabolites. This may cause the onset of gut disorders that can be manifest through both acute and chronic conditions. Moreover, the gut flora may become contaminated by transient pathogens that serve further to upset the normal community structure. There has been a recent increase in the use of dietary components that help to maintain, or even improve, the gut microflora "balance. " Probiotics are live microbial feed supplements added to appropriate food vehicles (usually fermented milks), whereas prebiotics are dietary carbohydrates that have a selective metabolism in the colon and serve to increase numbers of bacteria seen as desirable. Because of their purported health-promoting properties, lactic acid-producing bacteria, including bifidobacteria, are the usual target organisms. The market value and biological potential of both approaches are enormous. This article will summarize how efficacious types can be identified.
The dollar/euro exchange rate

While the practical policies toward the exchange rate of the Fed and the ECB are very similar, there is a major philosophical difference between the American view that governments have no business to worry about capital flows and exchange rates versus the European view that these things matter and that floating is simply not defending a particular rate. Under the first view, the only issue is what determines the exchange rate. The literature has concluded that not much can be said about this in the short run, but that in the long run misaligned rates tend to return toward equilibrium (“PPP”). Under the second view, it makes sense to ask what is the “fundamental equilibrium exchange rate” (or some FEER-like concept). Most of the evidence suggests that the dollar/euro rate at the time of writing the article ($1.27) represented at most a modest overshooting.
Dynamic microtubules regulate cellular contractility during T-cell activation

Significance T-cell activation is an essential event in the adaptive immune response to fight against infections. T cells were recently shown to be mechanosensitive, and to exert forces actively on the opposing antigen-presenting cell during activation. However, the molecular basis of force generation by T cells is poorly understood. Here, we report a molecular mechanism that involves the T-cell microtubule (MT) and actomyosin cytoskeletons, which interact through Rho GTPase activity. Our study highlights the role played by the MT cytoskeleton in regulating actomyosin-generated forces, which play a key role in T-cell activation. T-cell receptor (TCR) triggering and subsequent T-cell activation are essential for the adaptive immune response. Recently, multiple lines of evidence have shown that force transduction across the TCR complex is involved during TCR triggering, and that the T cell might use its force-generation machinery to probe the mechanical properties of the opposing antigen-presenting cell, giving rise to different signaling and physiological responses. Mechanistically, actin polymerization and turnover have been shown to be essential for force generation by T cells, but how these actin dynamics are regulated spatiotemporally remains poorly understood. Here, we report that traction forces generated by T cells are regulated by dynamic microtubules (MTs) at the interface. These MTs suppress Rho activation, nonmuscle myosin II bipolar filament assembly, and actin retrograde flow at the T-cell–substrate interface. Our results suggest a novel role of the MT cytoskeleton in regulating force generation during T-cell activation.
Coffee marketing cooperatives and rural poverty alleviation: Evidence from Southern Ethiopia

In this chapter we examine the determinants of cooperative membership and its welfare effects among small-scale coffee growers. Data collection has taken place in Sidama Zone, Southern Ethiopia, using a detailed household survey. We have found the following important variables determining farmers’ participation in coffee marketing cooperatives: age of the household head, land size, household size and educational level of the household head. With regards to welfare impacts, our findings reveal that while cooperative members obtain higher prices and have a higher coffee income, there are no significant differences between them and the control group in relation to coffee productivity, access to credits, savings or technical assistance.
Economic Dynamics in Transitional Economies: The Four-P Governments, the EU Enlargement, and the Bruxelles Consensus

* Foreword * Preface * Acknowledgments * Abbreviations and Acronyms * Introduction * The Regional Context * The Purpose of This Book * Liberalization and Economic Hopes * Synopsis * Chapter 1. The Political Economy in Europe: The Three-P Governments * Introduction * A Formalized Methodology of Analysis * The Microfoundations of Monetary Games * Credibility and Inconsistency * Inconsistency and Institutional Devices Toward Credibility * The Eastern and Western Evidence * Chapter 2. Accepting a Challenge: Joining the Western European Club * Introduction * Interactions and Conflicts in Economic Choices * Structural Economic Convergence: An Alternative Approach * Trade and Financial Integration * Estimation Results * Toward a Political Economy of Integration * Chapter 3. Developments in Transitional Economies: "Syndromes" and Structural Breaks * Introduction * The Decisive Disputes * Economic Slumps and The Syndromes * The Underground Economy: A Syndrome? * The Other Syndromes * The Transformation up to the End of the 1990s * From the 1990s to an Economy Without Syndromes * Chapter 4. The Political Economy of Keynes, Schumpeter, and the Supply-Siders * Introduction * Provoking a Supply Response * Recovery Persistence * Common Fears * Political Economy Conclusions * Chapter 5. The Bruxelles Consensus and the Fourth-P Government * Introduction * The Definitive Issues * A New Consensus versus a Second Lab Experience * Is the Transformation Over? * The Fourth-P Government * A Paradigm for the Next Decade * Appendix. Relevant Internet Addresses: Widening of the EU's Boundaries * Notes * References * Index
Optimized uplink-downlink decoupling in LTE-U networks: An echo state approach

Uplink-downlink decoupling in which users can be associated to different base stations in the uplink and downlink in heterogeneous small cell networks (SCNs) has attracted significant attention recently. However, most existing works focus on simple association mechanisms in LTE SCNs that operate only in the licensed band. In contrast, in this paper, the problem of resource allocation with uplink-downlink decoupling is studied for an SCN that incorporates LTE in the unlicensed band (LTE-U). Here, the users can access both licensed and unlicensed bands while being associated to different base stations. This problem is formulated as an optimization problem which jointly incorporates user association, spectrum allocation, and load balancing. To solve this problem, a distributed algorithm based on the machine learning framework of echo state networks is proposed using which the small base stations autonomously choose their optimal bands allocation strategies while having only limited information on the network's and users' states. Simulation results show that the proposed approach yields significant gains, in terms of total rate, that reach up to 41% and 54%, respectively, compared to Q-learning and nearest neighbor algorithms. The results also show that ESN significantly improves convergence time of up to 17% compared to Q-learning.
Visualization of three-dimensional maps

A three-dimensional map is a partition of a 3D manifold into topological polyhedra. We consider the problem of visualizing the topology of a three-dimensional map given only its combinatorial description. Our solution starts by automatically constructing a "nice" geometric realization of the map in R/sup m/, for some m/spl ges/4. The geometric realization is chosen by optimizing certain aesthetic criteria, measured by energy functions. We then project this model to R/sup 3/, and display the resulting multi-celled solid object with a variety of specialized rendering techniques.
Portfolio Diversification and Selectivity Performance of Fund Managers in India - A Study of Select Equity Funds

This article discusses the portfolio diversification of top 10 sectors of sample funds and evaluates selective abilities of Indian fund managers of select Equity large Cap and Small and Mid Cap funds. Researcher emphasized on secondary data only and selected 12 equity funds; 6 Large Caps and 6 Small and Mid Caps, selected from 6 Mutual fund houses 2 from public sector and 4 from private sector using purposive sampling. To know the degree of diversification R Square is used and to measure Selectivity performance Jensen’s Alpha and Fama’s Measure of decomposition was applied and found out that, during the study period 67.67% sample funds fund managers have superior stock selection ability and 33.33% were in lack of selection skills. Keywords: R Square, Diversification, Jensen’s Alpha, Fama’s Measure of decomposition, Selectivity, Net selectivity, selectivity performance.