Miracle-dz/UniFAR-FTUs huggingface dataset:
Gata3 restrains B cell proliferation and cooperates with p18INK4c to repress B cell lymphomagenesis

GATA3, a lineage specifier, controls lymphoid cell differentiation and its function in T cell commitment and development has been extensively studied. GATA3 promotes T cell specification by repressing B cell potential in pro T cells and decreased GATA3 expression is essential for early B cell commitment. Inherited genetic variation in GATA3 has been associated with lymphoma susceptibility. However, it remains elusive how the loss of function of GATA3 promotes B cell development and induces B cell lymphomas. In this study, we found that haploid loss of Gata3 by heterozygous germline deletion increased B cell populations in the bone marrow (BM) and spleen, and decreased CD4 T cell populations in the thymus, confirming that Gata3 promotes T and suppresses B cell development. We discovered that haploid loss of Gata3 reduced thymocyte proliferation with induction of p18Ink4c (p18), an inhibitor of CDK4 and CDK6, but enhanced B cell proliferation in the BM and spleen independent of p18. Loss of p18 partially restored Gata3 deficient thymocyte proliferation, but further stimulated Gata3 deficient B cell proliferation in the BM and spleen. Furthermore, we discovered that haploid loss of Gata3 in p18 deficient mice led to the development of B cell lymphomas that were capable of rapidly regenerating tumors when transplanted into immunocompromised mice. These results indicate that Gata3 deficiency promotes B cell differentiation and proliferation, and cooperates with p18 loss to induce B cell lymphomas. This study, for the first time, reveals that Gata3 is a tumor suppressor specifically in B cell lymphomagenesis.
Bootstrapped Thompson Sampling and Deep Exploration

This technical note presents a new approach to carrying out the kind of exploration achieved by Thompson sampling, but without explicitly maintaining or sampling from posterior distributions. The approach is based on a bootstrap technique that uses a combination of observed and artificially generated data. The latter serves to induce a prior distribution which, as we will demonstrate, is critical to effective exploration. We explain how the approach can be applied to multi-armed bandit and reinforcement learning problems and how it relates to Thompson sampling. The approach is particularly well-suited for contexts in which exploration is coupled with deep learning, since in these settings, maintaining or generating samples from a posterior distribution becomes computationally infeasible.
Nonparametric methods in economics and finance : dependence, causality and prediction

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Cryptic density dependence: effects of spatio-temporal covariation between density and site quality in reef fish

The importance and strength of density dependence continues to engender debate because of its central importance to population dynamics and regulation. Here, we show how confounding effects of site quality can mask strong effects of density dependence. In particular, we explore spatiotemporal variation and covariation among (1) densities of newly settled coral reef fish (Thalassoma hardwicke), (2) environmental characteristics, and (3) the strength of density-dependent mortality. Environmental features of patch reefs were spatially and temporally variable and influenced density-dependent survival. Higher-quality sites (i.e., reefs possessing features that yield greater numbers of recruits at any given settlement level) received greater settlement, and this relationship masked the operation of density dependence when variation in quality among sites (or times) was not distinguished (a common approach in many Observational studies of density dependence). Our work illustrates how spatiotemporal covariation in settlement density and site quality can obscure patterns of density dependence at larger scales, contributing to a phenomenon we call "cryptic density dependence. " Acknowledging patterns and consequences of covariance may alter the way we study population dynamics, especially of marine organisms, where the link between processes that affect settlement and post-settlement survival remains relatively poorly understood.
Limits to the performance of software shared memory: a layered approach

Much research has been done in fast communication on clusters and in protocols for supporting software shared memory across them. However, the end performance of applications that were written for the more proven hardware-coherent shared memory is still not very good on these systems. Three major layers of software (and hardware) stand between the end user and parallel performance, each with its own functionality and performance characteristics. They include the communication layer, the software protocol layer that supports the programming model, and the application layer. These layers provide a useful framework to identify the key remaining limitations and bottlenecks in software shared memory systems, as well as the areas where optimization efforts might yield the greatest performance improvements. This paper performs such an integrated study, using this layered framework, for two types of software distributed shared memory systems: page-based shared virtual memory (SVM) and fine-grained software systems (FG). For the two system layers (communication and protocol), we focus on the performance costs of basic operations in the layers rather than on their functionalities. This is possible because their functionalities are now fairly mature. The less mature applications layer is treated through application restructuring. We examine the layers individually and in combination, understanding their implications for the two types of protocols and exposing the synergies among layers.
A study on relations between loops in sequences generated by the logistic map over integers and real numbers

We are interested in properties of the logistic maps with finite precision and theirs sequences. In this paper, we focus on a cyclic part, which we call a loop, in a sequence generated by the logistic map over integers successively, since the loop always exists in the sequence. We can observe loops in sequences generated by the logistic map with irrational numbers as initial values. We will show the relations between loops in sequences generated by the map over integers and real numbers. We will also show a correspondence between these loops by averages of squared differences.
Simvastatin modulates cellular components in influenza A virus-infected cells

Influenza A virus is one of the most important health risks that lead to significant respiratory infections. Continuous antigenic changes and lack of promising vaccines are the reasons for the unsuccessful treatment of influenza. Statins are pleiotropic drugs that have recently served as anti-influenza agents due to their anti-inflammatory activity. In this study, the effect of simvastatin on influenza A-infected cells was investigated. Based on the MTT cytotoxicity test, hemagglutination (HA) assay and qPCR it was found that simvastatin maintained cell viability and decreased the viral load significantly as compared to virus-inoculated cells. The expression of important pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6 and interferon-γ), which was quantified using ELISA showed that simvastatin decreased the expression of pro-inflammatory cytokines to an average of 2-fold. Furthermore, the modulation of actin filament polymerization was determined using rhodamine staining. Endocytosis and autophagy processes were examined by detecting Rab and RhoA GTPase protein prenylation and LC3 lipidation using western blotting. The results showed that inhibiting GTPase and LC3 membrane localization using simvastatin inhibits influenza replication. Findings of this study provide evidence that modulation of RhoA, Rabs and LC3 may be the underlying mechanisms for the inhibitory effects of simvastatin as an anti-influenza compound.
Infectious mononucleosis and corticosteroids: management practices and outcomes.

OBJECTIVE Although many studies have examined the effects of systemic corticosteroid therapy (SCT) on the clinical course of infectious mononucleosis (IM), few have evaluated the influence of these studies on treatment patterns and outcomes. The purpose of this study was to review current therapeutic strategies and outcomes in uncomplicated and complicated IM. DESIGN Retrospective case series. SETTING Tertiary care center. PATIENTS We identified 206 immunocompetent patients with IM diagnosed during the previous 5 years. Patient information, including age, sex, history and physical findings at presentation, pertinent laboratory data, management practices, and treatment outcomes, were analyzed. INTERVENTIONS Systemic corticosteroid therapy was used in 44.7% of patients. Evaluation of treatment indications for SCT revealed that 8.0% of the study population qualified by traditional criteria for the use of corticosteroids; 92.0% of patients received SCT for other indications. Factors associated with the observed increase in corticosteroid use included a history of repeat visits, inpatient admission, and otolaryngology consultation. MAIN OUTCOME MEASURES Diagnosis was made on the basis of a positive heterophil antibody test (monospot test) with appropriate clinical findings (97.5% of patients) or by the presence of lymphocytosis with appropriate clinical findings (2.4% of patients). RESULTS Systemic corticosteroid therapy was not positively associated with fever, decreased oral intake, tonsillar hypertrophy, or duration of symptoms. No significant differences in incidence of disease complications, rates of hospital admission, or length of hospital stay were noted between the steroid and nonsteroid treatment groups. CONCLUSIONS Despite consistent and uniform acceptance in the medical literature that SCT in the setting of IM should be reserved for patients with impending airway obstruction, corticosteroids continue to be used on a much broader scale at this tertiary care institution. This observation suggests that clinicians see value in SCT for treatment of IM beyond the classically accepted reasons. Moreover, despite previous reports of possible adverse consequences of SCT in IM, our review failed to demonstrate any such trend.
Cognitive flexibility and long-term depression (LTD) are impaired following β-catenin stabilization in vivo

Significance Complex learning and memory are believed to require the weakening or elimination of synapses in the brain, a process mediated by adhesion molecules, which maintain synapse strength and stability. In the present study, we examine in vivo the effects of stabilization of β-catenin, an intracellular protein that is a component of the cadherin adhesion complex. We find that stabilization of β-catenin in the brain prevents normal activity-dependent downscaling of synapse strength, resulting in a striking impairment in cognitive flexibility. These results demonstrate that β-catenin plays an important role in learning and memory and that aberrant increases in synaptic adhesion can have detrimental effects on cognitive function. The cadherin/β-catenin adhesion complex is a key mediator of the bidirectional changes in synapse strength which are believed to underlie complex learning and memory. In the present study, we demonstrate that stabilization of β-catenin in the hippocampus of adult mice results in significant impairments in cognitive flexibility and spatial reversal learning, including impaired extinction during the reversal phase of the Morris water maze and deficits in a delayed nonmatch to place T-maze task. In accordance with these deficits, β-catenin stabilization was found to abolish long-term depression by stabilizing cadherin at the synaptic membrane and impairing AMPA receptor endocytosis, while leaving basal synaptic transmission and long-term potentiation unaffected. These results demonstrate that the β-catenin/cadherin adhesion complex plays an important role in learning and memory and that aberrant increases in synaptic adhesion can have deleterious effects on cognitive function.
Attenuation of VEGFR-2 Expression by sFlt-1 and Low Oxygen in Human Placenta

Vascular endothelial growth factor receptor 2 (VEGFR-2), the primary receptor for VEGF, is crucial for normal endothelial function. sFlt-1, a truncated and soluble form of VEGFR-1 which binds and inhibits VEGF, is increased in preeclampsia and is positively regulated by low oxygen. Here, we investigated the effects of sFlt-1 and hypoxia on VEGFR-2 expression and signaling in the human placenta. VEGFR-2 transcript and protein levels were significantly decreased in preeclamptic placentae compared to controls (1.82 and 1.85 fold, respectively). An inverse correlation was observed for VEGFR-2 and sFlt-1 levels in both singleton and twin placentae from patients with preeclampsia. Immunofluorescence analyses revealed co-localization of VEGFR-2 and sFlt-1 in placental vasculature and co-immunoprecipitation analyses confirmed VEGFR-2 and sFlt-1 interaction only in preeclamptic placentae compared to age-matched controls. VEGFR-2 transcript and protein levels from explants cultured in 3% O2 were significantly decreased compared to those incubated at 20% O2 (5.9 and 12.47 fold, respectively). Also, VEGFR-2 transcript levels were significantly decreased in early first trimester placentae (low oxygen environment) compared to late first trimester placentae (2.05 fold). We next explored whether sFlt-1 directly affects VEGFR-2 expression. Treatment of first trimester placental explants with sFlt-1 resulted in significantly decreased levels of VEGFR-2 (2.03 fold) and downstream signaling proteins phospho-ERK (1.60 fold) and phospho-Akt (1.64 fold). Our findings show a novel hypoxia-induced and PE-related down-regulation of VEGFR-2 in the human placenta. sFlt-1, which is known to be increased in hypoxic conditions and PE, directly attenuates VEGFR-2 expression and signaling. A direct interaction between sFlt-1 and VEGFR-2 may represent an important mechanism in VEGFR-2 regulation, inhibition of VEGFR-2-mediated processes in placentation and a novel platform to examine the onset of preeclampsia.
ABS: adaptative borders search of frequent itemsets

In this paper, we present an ongoing work to discover maximal frequent itemsets in a transactional database. We propose an algorithm called ABS for Adaptive Borders Search, which is in the spirit of algorithms based on the concept of dualization. From an abstract point of view, our contribution can be seen as an improvement of the basic APRIORI algorithm for mining maximal frequent itemsets. The key point is to decide dynamically at which iteration, if any, the dualization has to be made to avoid the enumeration of all subsets of large maximal itemsets. Once the first dualization has been done from the current negative border, APRIORI is no longer used and instead, another dualization is carried out from the positive border known so far. The process is repeated until no change occurs anymore in the positive border in construction. Experiments have been done on FIMI datasets from which tradeoffs on adaptive behavior have been proposed to guess the best iteration for the first dualization. Far from being the best implementation wrt FIMI'03 contributions, performance evaluations of ABS exhibit better performance than IBE, the only public implementation based on the concept of dualization.
How Governments Retrench in Crisis: The Case of Ireland

The Irish experience of fiscal retrenchment under crisis conditions poses new questions of governance, the evolving answers to which are likely to involve importance changes in the state’s organizational profile and in its policy competences. The government is required to formulate and implement extremely tough choices, particularly since Ireland entered an EU-IMF loan programme in November 2010. Yet government does retain some policy discretion in the priorities it adopts in the composition of budget adjustment and in the distributive impact of cuts. This paper sets out to explore where the adjustments have been made through examination both of the composition of budgets and of the organizational configuration of state institutions, and it analyses how these outcomes can be accounted for. The paper draws upon a new official database setting out a detailed compositional analysis of Irish public spending between 2008 and 2012, and upon the Irish State Administration Database (http://isad.ie) through which the organizational aspects of the state's policy capacity can be analysed.
Migratory patterns of sympathetic ganglioblasts and other neural crest derivatives in chick embryos

While it is well established that neural crest cells migrate to give rise to a variety of cell types and tissues, the migratory patterns among individual neural crest derivatives have not been fully worked out. Such knowledge is important not only in relation to the mechanisms of neural crest migration and differentiation, but also in understanding the ontogeny of the PNS. Of special interest in the latter regard is the origin of sympathetic ganglion cells and their innervation, since studies on ganglion cell innervation have suggested that the matching between pre- and postganglionic neurons might be based on their early positions along the neuraxis (see preceding paper). In the present study, I have used the quail-chick transplantation technique to examine the migratory patterns of the precursors of sympathetic ganglion cells, dorsal root ganglion cells, and melanocytes that originate from 1 or 2 segments of the trunk neural crest. My results indicate that precursors of sympathetic ganglion cells, on average, migrate 2 segments rostrally and 3 segments caudally. Thus, individual sympathetic ganglia comprise neurons that originate from up to 6 segments of the neuraxis. Precursors of melanocytes also migrate along the rostrocaudal axis, but to an even greater extent than sympathetic ganglioblasts. In contrast, precursors of dorsal root ganglion cells do not migrate at all along the rostrocaudal axis (although they migrate along a ventromedial pathway to give rise to the dorsal root ganglia of the same segmental level). The number of neural crest segments contributing to each sympathetic ganglion is approximately equal to the number of spinal cord segments contributing to its innervation. (ABSTRACT TRUNCATED AT 250 WORDS)
The Rodney L. White Center for Financial Research Are Stars' Opinions worth More? the Relation between Analyst Reputation and Recommendations Values Are Stars' Opinions worth More? the Relation between Analyst Reputation and Recommendation Values

We study the effect of personal reputation on the values of analysts' stock recommendations using the 1994-2003 U.S. data. All-American (AA) analysts' buy recommendations earn significantly positive abnormal returns over the 10-year period. Buy recommendations of analysts at top-tier banks also earn significantly positive abnormal returns, but only AAs contribute to this out-performance; top-tier non-AAs' buy recommendations do not provide positive abnormal returns. Interestingly, sell recommendations made by all four subgroups of analysts (top-tier AA, top-tier non-AA, lower-status AA, lower-status non-AA) have significant investment value. Among them, top-tier-bank analysts out-perform lower-status-bank analysts. Comparing investment performances across groups, we find that top-tier AAs out-perform all the other groups in both buy and sell category. The value of their recommendation is economically significant. For buys, they out-perform the market by 6.12% per year in raw returns, and by 4.35% and 2.59% per year in market-and Fama-French three-factor adjusted returns, respectively. For sells, their market-and three-factor-adjusted returns are 3.56% and 6.9% per year, respectively. These results indicate that active sell-side research has value, and that personal reputation is positively related to recommendation value. We document evidence consistent with the existence of conflict of interest in top-tier investment banks. We find that buy recommendations made by top-tier non-AAs out-perform all other groups in the peak year of 1999, but they yield the negative and the lowest abnormal returns in the subsequent trough of 2000. Since top-tier analysts generally have superior skill, this volatile performance pattern is consistent with top-tier non-AAs aggressively touting " glamour " stocks during market booms and subsequently being reluctant to downgrade their former champion stocks in the following bear market. In contrast, since top-tier AAs' recommendations remain valuable during the troughs of the market, our results indirectly suggest that personal reputation, as indicated by the AA status, can play a mitigating role in the conflict of interest problem and thus has a net positive effect on the value of analysts' stock recommendations.
Associations between primary healthcare and unplanned medical admissions in Norway: a multilevel analysis of the entire elderly population

Objective To examine if individual risk of unplanned medical admissions (UMAs) was associated with municipality general practitioner (GP) or long-term care (LTC) volume among the entire Norwegian elderly population. Design Cross-sectional population-based study. Setting 428 of 430 Norwegian municipalities in 2009. Participants All Norwegians aged ≥65 years (n=721 915; 56% women—15% of the total population). Main outcome measure Individual risk of UMA. Results Using a multilevel analytical framework, consisting of individuals (N=722 464) nested within municipalities (N=428), nested within local hospital areas (N=52) we found no association between municipality GP or LTC volume and UMAs. However, we found that higher LTC levels of provision were associated with fewer hospitalisations among the older age groups. A modest geographical variability was observed for UMA in adjusted analysis. Conclusions A higher primary healthcare volume was only associated with fewer UMAs among the oldest old in a universally accessible healthcare system.
A Reappraisal of the U.S. Clinical Trials of Post-Treatment Lyme Disease Syndrome

Four federally funded randomized placebo-controlled treatment trials of post-treatment Lyme syndrome in the United States have been conducted. Most international treatment guidelines summarize these trials as having shown no acute or sustained benefit to repeated antibiotic therapy. The goal of this paper is to determine whether this summary con-clusion is supported by the evidence. Methods: The methods and results of the 4 U.S. treatment trials are described and their critiques evaluated. Results: 2 of the 4 U.S. treatment trials demonstrated efficacy of IV ceftriaxone on primary and/or secondary outcome measures. Conclusions: Future treatment guidelines should clarify that efficacy of IV ceftriaxone for post-treatment Lyme fatigue was demonstrated in one RCT and supported by a second RCT, but that its use was not recommended primarily due to adverse events stemming from the IV route of treatment. While repeated IV antibiotic therapy can be effective, safer modes of delivery are needed.