Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of Recombinant Vesicular Stomatitis Viruses That Exploit Defects in Host Defense To Augment Specific Oncolytic Activity

ABSTRACT Vesicular stomatitis virus (VSV) is a negative-stranded RNA virus normally sensitive to the antiviral actions of alpha/beta interferon (IFN-α/β). Recently, we reported that VSV replicates to high levels in many transformed cells due, in part, to susceptible cells harboring defects in the IFN system. These observations were exploited to demonstrate that VSV can be used as a viral oncolytic agent to eradicate malignant cells in vivo while leaving normal tissue relatively unaffected. To attempt to improve the specificity and efficacy of this system as a potential tool in gene therapy and against malignant disease, we have genetically engineered VSV that expresses the murine IFN-β gene. The resultant virus (VSV-IFNβ) was successfully propagated in cells not receptive to murine IFN-α/β and expressed high levels of functional heterologous IFN-β. In normal murine embryonic fibroblasts (MEFs), the growth of VSV-IFNβ was greatly reduced and diminished cytopathic effect was observed due to the production of recombinant IFN-β, which by functioning in a manner involving autocrine and paracrine mechanisms induced an antiviral effect, preventing virus growth. However, VSV-IFNβ grew to high levels and induced the rapid apoptosis of transformed cells due to defective IFN pathways being prevalent and thus unable to initiate proficient IFN-mediated host defense. Importantly, VSV expressing the human IFN-β gene (VSV-hIFNβ) behaved comparably and, while nonlytic to normal human cells, readily killed their malignant counterparts. Similar to our in vitro observations, following intravenous and intranasal inoculation in mice, recombinant VSV (rVSV)-IFNβ was also significantly attenuated compared to wild-type VSV or rVSV expressing green fluorescent protein. However, VSV-IFNβ retained propitious oncolytic activity against metastatic lung disease in immunocompetent animals and was able to generate robust antitumor T-cell responses. Our data indicate that rVSV designed to exploit defects in mechanisms of host defense can provide the basis for new generations of effective, specific, and safer viral vectors for the treatment of malignant and other disease.
Maternal thyroid function at 11 to 13 weeks of gestation and subsequent fetal death.

BACKGROUND Studies have shown that overt hypothyroidism is associated with a substantial risk of miscarriage. There is controversy as to whether subclinical hypothyroidism has the same effect and whether such effect is mediated by the presence of antithyroid antibodies. Our hypothesis is that maternal thyroid function in the first trimester is altered in pregnancies ending in miscarriage or fetal death. METHODS Thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine, anti-thyroperoxidase antibody, and anti-thyroglobulin antibody at 11-13 weeks of gestation were measured in 202 singleton pregnancies that subsequently resulted in miscarriage or fetal death, and the values were compared with the results of 4318 normal pregnancies. RESULTS In the fetal loss group, compared to the unaffected group, there was an increase in median TSH multiple of the normal median (1.133 vs. 1.007 MoM), decrease in median FT4 MoM (0.958 vs. 0.992 MoM), and increase in the incidence of TSH above the 97.5th centile (5.9% vs. 2.5%) and FT4 below the 2.5th centile (5.0% vs. 2.5%). Logistic regression analysis demonstrated that in the prediction of fetal loss there were significant contributions from FT4 MoM, maternal black ethnic origin, history of chronic hypertension, and use of ovulation drugs. The prevalence of antithyroid antibody positivity was not significantly different in the fetal loss group compared to that of normal pregnancies (15.3% vs. 16.8%). CONCLUSIONS Impaired thyroid function may predispose to miscarriage and fetal death.
Politics, Economics and Saudi Military Intervention in Bahrain

Abstract The March 14, 2011 Saudi military intervention in Bahrain to suppress pro-democracy uprisings created serious regional and global concerns. Political analysts and commentators have interpreted the Saudi intervention primarily in terms of domestic and regional political and strategic dynamics. This paper analyses the intervention issue from both political and economic perspectives and argues that the Saudi decision to intervene in Bahrain to trample the democratic rights of common Bahrainis was no less, if not more, influenced by economic factors than political and strategic calculations. Moreover, similar Saudi interventions in other Gulf Cooperation Council countries remain a reality if the status quo is seriously threatened by any internal pro-democracy forces, with or without external support.
Continuous Analysis of Repolarization Characteristics during Insulin Induced Hypoglycemia

Hypoglycemia has been shown to affect ECG. Reported changes are prolongation of QT-interval and increased R/T amplitude ratio. These ECG changes are suggested to be connected to so-called dead in bed syndrome. Continuous analysis of ECG changes and blood glucose values, during insulin induced hypoglycemia is presented. Altogether 22 subjects were analyzed in three different groups; 1) healthy group 2) diabetic patients diagnosed less 5 years ago and 3) chronic diabetics diagnosed over than 5 years ago. The results showed that 20 of 22 subjects’ QT-time was prolonged during hypoglycemia. In addition, in group 3 changes were smaller than in groups 1 and 2.
Weight-based victimization toward overweight adolescents: observations and reactions of peers.

BACKGROUND Weight-based victimization has become increasingly reported among overweight youth, but little is known about adolescents' perceptions and observations of weight-based teasing and bullying. This study examined adolescents' observations of and reactions to weight-based victimization toward overweight students at school. METHODS Adolescents (N = 1555) at 2 high schools in central Connecticut completed a questionnaire that examined their perceptions of how common weight-based victimization is compared to other forms of teasing at school, what types of weight-based teasing are frequently observed, who typical perpetrators of weight-based victimization are, and their own reactions to observed teasing incidents. Participants also completed the Fat Phobia Scale. RESULTS Participants perceived being overweight as a primary reason that peers are victimized at school. At least 84% of participants observed overweight students being teased in a mean way and teased during physical activities, and 65% to 77% of students observed overweight and obese peers being ignored, avoided, excluded from social activities, having negative rumors spread about them, and being teased in the cafeteria. Most students also observed verbal threats and physical harassment toward overweight and obese students. Although the majority of participants felt comfortable stepping in to help an overweight peer who has been teased, many remain passive bystanders following these incidents. CONCLUSION Youth perceive frequent and multiple forms of weight-based victimization. Schools' efforts to address weight bias and assist overweight and obese students are important.
Inventory Planning for a Modular Product Family

This paper is motivated by observing that an increasing number of firms are offering modular products assembled with multiple option choices for the consumer. Starting with the PC offerings by Dell which allowed (and still allows) users to configure their product by choosing among multiple choices for each option, the current market place seems to have evolved to a make‐to‐stock scenario where Apple offers its IPAD series with multiple models each with a unique storage size, color, and wireless chip technology. The focus of our work is on determining the optimal stocking level of modular end‐products. Our analysis is based on a benchmark model with the aim of maximizing expected profit subject to an aggregate fill rate constraint as well as variant‐specific individual fill rates under a make‐to‐stock setting. To further assess the robustness of our finding, we consider the extensions of correlated market preferences over options, price‐dependent demand, and alternative probability distributions for characterizing uncertainty in market preferences or aggregate demand. Finally we also show how to extend the single period model into a multiple‐period setting. Through extensive computational analysis, we find that more precise estimates of market preferences for various modular options constitute extremely valuable information that goes beyond the usefulness of forecasts of aggregate market demand. From a practical perspective, this might be indicative of another classic marketing‐operations trade‐off. Offering more options for consumers would be preferred by marketing managers since this would reach more consumers and hence, enhance product sales. On the other hand, the ability to obtaining greater forecast accuracy would decline when the number of options increase. Hence, from an operational perspective, it would be preferred to limit option choices (so that better forecasts can be obtained) since this would lead to lower stocking costs and hence, higher profits.
CEO Succession Mechanisms, Organizational Context, and Performance: A Socio‐Emotional Wealth Perspective on Family‐Controlled Firms

This article extends the literature on CEO succession and financial performance by addressing corporate owners' mixed motives and desires to protect their interest in being in business. We draw on a Socio-Emotional Wealth (SEW) perspective to investigate how the choice of one of three succession mechanisms – relay succession, ‘horse races’ among internal CEO candidates, and hiring from outside – may effectively balance trade-offs between corporate owners' non-financial SEW motives and the firm's financial performance. We find that implementing one of these succession mechanisms reduces the negative impact that typically characterizes CEO transitions in family firms. We also show that family presence on the board of directors offsets the benefits of having selected these balancing succession mechanisms, in either placing too much emphasis on SEW, or creating negative dynamics that make the chosen succession mechanisms less effective.
Performance of newcomers in highly interdependent teams: the case of basketball teams

Abstract Sports teams have to continually change their player rosters in order to be competitive. As the hiring of new players is a high financial investment, team managers need to increase their understanding about newcomer performance. With this purpose, this study is focused on newcomers' performance in the interactive environment of basketball teams. This work tested a multilevel model using longitudinal data from 132 newcomers in 30 National Basketball Association teams. The results of this study may be especially appealing for sports team coaches by showing how newcomers improved their initial performance after they had spent sufficient time playing with other team members. In addition, the results show that how a high prior performance of the current members may make newcomers' adaptation harder, involving a negative effect on the initial performance of the newcomers. These results should be useful for team managers who have to plan the season and make hiring decisions.
Adipogenic Differentiation of hMSCs is Mediated by Recruitment of IGF‐1r Onto the Primary Cilium Associated With Cilia Elongation

Primary cilia are single non‐motile organelles that provide a highly regulated compartment into which specific proteins are trafficked as a critical part of various signaling pathways. The absence of primary cilia has been shown to prevent differentiation of human mesenchymal stem cells (hMSCs). Changes in primary cilia length are crucial for regulating signaling events; however it is not known how alterations in cilia structure relate to differentiation. This study tested the hypothesis that changes in primary cilia structure are required for stem cell differentiation. hMSCs expressed primary cilia that were labeled with acetylated alpha tubulin and visualized by confocal microscopy. Chemically induced differentiation resulted in lineage specific changes in cilia length and prevalence which were independent of cell cycle. In particular, adipogenic differentiation resulted in cilia elongation associated with the presence of dexamethasone, while insulin had an inhibitory effect on cilia length. Over a 7‐day time course, adipogenic differentiation media resulted in cilia elongation within 2 days followed by increased nuclear PPARγ levels; an early marker of adipogenesis. Cilia elongation was associated with increased trafficking of insulin‐like growth factor‐1 receptor β (IGF‐1Rβ) into the cilium. This was reversed on inhibition of elongation by IFT‐88 siRNA transfection, which also decreased nuclear PPARγ. This is the first study to show that adipogenic differentiation requires primary cilia elongation associated with the recruitment of IGF‐1Rβ onto the cilium. This study may lead to the development of cilia‐targeted therapies for controlling adipogenic differentiation and associated conditions such as obesity. Stem Cells 2015;33:1952–1961
UK direct investment in the United States: a mode of entry analysis

This article investigates the reasons underlying the high propensity of UK firms to directly invest in the United States via acquisition and merger. Using a binomial logit model, this study analyses data from 142 firms in five industrial sectors over the period 1984–1994. Together, these sectors account for more than 80% of UK foreign direct investment (FDI) in the sample period. The results highlight the role of diversification in explaining this behaviour. In contrast, the relative lack of evidence to support the role of exchange rates and leverage in influencing the decision to merge/acquire continues to fuel division as to the role of capital market imperfections in determining mode of entry.
Environmental Contamination with Vancomycin-Resistant Enterococci from Hospital Sewage in Portugal

ABSTRACT Vancomycin-resistant enterococci (VRE) were detected in samples of sewage obtained downstream of hospitals of the Porto area in Portugal, and in samples from the Douro Estuary. Clonal analysis, Tn1546 typing, and presence of putative virulence traits indicate the clinical origin of these isolates. This observation highlights the importance of hospital sewage in the VRE contamination of the environment.
Test‐retest reliability of balance tests in children with cerebral palsy

To investigate intrasession and intersession reliability of balance tests in children with or without disabilities, 50 children without disabilities (ND) and 36 children with cerebral palsy (CP) aged from 5 to 12 years were tested. Intrasession reliability of postural stability of the Smart Balance Master System and one‐leg standing test were assessed in both groups and intersession reliability of the Smart Balance Master System and balance subtest of the Bruininks‐Oseretsky Test of Motor Proficiency (BOTMP) were assessed in ND children. Intersession reliability of the postural stability test in ND children, obtained using the Smart Balance Master System, was of moderate to good reliability in centre target (CT), sway vision (SV), eyes open and sway surface (EOSS), and sway vision and sway surface (SVSS; ICC 0.72 to 0.84). In children with CP, intrasession reliability was high in CT (ICC 1). One‐leg standing tests in both groups also had moderate to good intersession reliability (ICC 0.56 to 0.99). Agreement of failure score of lateral rhythmic shifting (LRS) at 1 second and 2 seconds pace was 85% and 93% respectively in ND children. Within the balance subtest of BOTMP, only two items had 100% agreement. Results suggest that postural stability tests in four conditions (CT, SV, EOSS, and SVSS), LRS, one‐leg standing, and walking on a line are reliable and can be used to monitor balance control in ND children. Postural stability in CT condition and one‐leg standing test are reliable in children with CP. Further study is needed to establish more reliable balance tests for children with CP.
Corporate governance and the current crisis

Purpose – This paper seeks to look at “the crisis” in terms of a failure of corporate governance.Design/methodology/approach – The paper relies on data summarized from personal interviews with directors of financial institutions in the aftermath of September 2008. It takes an interpretive approach and mediates the date to unpick the crisis in terms of governance at four levels.Findings – The paper suggests that a multivariate quality management may be a positive reaction to the crisis.Originality/value – The paper offers insights based on privileged original data from senior managers.
On the relationship between gender disparities in scholarly communication and country-level development indicators

Gender disparities in science remain, despite decades of policies aimed at achieving gender parity. Yet, little is known about the macro-level factors affecting such disparities. This paper examines the degree to which country-level human development indicators (HDI) and gender inequality indicators (GII) gathered by the United Nations Development Report can reveal systemic gender inequalities in scholarship. Countries ‘low’ in HDI and GII had the lowest contribution of female participation in science and highest degree of international collaboration. Research from highly developed countries was more cited, although gender disparities remained. For HDI, gross national income was a strong predictor of scientific output and impact (and, to a lesser degree, collaboration). The rate of women in the labor force was the strongest predictive variable in GII, explaining differences in output, collaboration, and impact. However, predictive variables differed by HDI/GII quartile, suggesting that monolithic policies may not be appropriate for addressing gender disparities in science.
Standing on the Shoulders of Giants: Cumulative Research and the Patent Law

Most innovators stand on the shoulders of giants, and never more so than in the current evolution of high technologies, where almost all technical progress builds on a foundation provided by earlier innovators. Most economics literature on patenting and patent races has looked at innovations in isolation, without focusing on the externalities or spillovers that early innovators confer on later innovators. But the cumulative nature of research poses problems for the optimal design of patent law that are not addressed by that perspective. The challenge is to reward early innovators fully for the technological foundation they provide to later innovators, but to reward later innovators adequately for their improvements and new products as well. This paper investigates the use of patent protection and cooperative agreements among firms to protect incentives for cumulative research.
Corporate Financial Policy, Information, and Market Expectations: An Empirical Investigation of Dividends

This paper documents a relationship between announcements of unexpected changes in financial policy and unexpec ted changes in performance of the firm. Using a new methodology that combines analysis of stock price movements and earnings forecast data the authors provide evidence that analysts revise their earnings fo recasts rationally following the announcement of an unexpected divide nd change by an amount positively related to the size of both the une xpected dividend change and the change in equity value surrounding th e announcement. The results provide direct evidence consistent with t he hypothesis that unexpected dividend changes signal information abo ut firm performance to market participants. Copyright 1987 by American Finance Association.
Measuring Effects of Trade Policy Distortions: How Far Have We Come?

After a brief review of the literature to the early 1970s, this paper assesses the contributions by economists during the past three decades to measuring the distortionary effects of trade policies. It does not pretend to be a comprehensive survey, but draws on selections from the literature that give a sense of the distance the profession has travelled from a trade policy practitioner's viewpoint since Corden's first paper on the subject in 1957. Phenomenal though that progress has been, there is ample room for further improvement in computing the economic (and other) effects of trade-related policies and their reform. The paper concludes with suggestions of where the priorities should be in global modelling of trade policy reform, as the world moves into the next round of multilateral trade negotiations.
Socioemotional Wealth Conflict in Family Firms

While Cruz, Larraza–Kintana, Garcés–Galdeano, and Berrone demonstrate how SEW can simultaneously elicit good and bad behavior in regard to corporate social responsibility, their findings also give rise to the idea that maintaining control and influence over day–to–day operations (internal socioemotional wealth [SEW]) and maintaining positive assessments of the firm's reputation (external SEW) may at times be in conflict. This commentary builds upon this notion by highlighting the need to explicitly examine SEW conflict, as well as offering initial theorizing on how family firms will pursue SEW preservation in these situations. Drawing on image theory, we theorize a process where preserving internal SEW is generally used as the guiding script in family firms because it is more salient on an everyday basis. However, we propose that if its preservation threatens the organization's identity and reputation, the script will be disrupted, precipitating a shift to preserving external SEW. The article concludes by discussing the broader theoretical implications of SEW conflict for family firms.
The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion

CD1d-restricted natural killer T (NKT) cells are a subset of regulatory T cells that react with glycolipid antigens. Although preclinical studies have effectively targeted NKT cells for immunotherapy, little is known regarding the early in vivo response of these cells to antigenic stimulation. We have analyzed the early response of NKT cells to glycolipid antigens and bacterial infection by using specific reagents for tracking these cells. Our results demonstrate dramatic in vivo expansion and surface phenotype alterations after NKT cell activation with α-galactosylceramide. In addition, we show significant NK1.1 down-modulation on NKT cells in the setting of oral Salmonella infection. Our results indicate that in vivo activation of NKT cells leads to a dynamic response characterized by surface receptor down-modulation and expansion. These findings alter current understanding of NKT cell biology and should aid in the rational design of NKT cell-based immunotherapies.
Measuring country event risk compensation on BRICs international portfolio management

The BRICs nations (Brazil, Russia, India and China) have a strong relative economic growth pattern in the world among economic powers. The allure of globalization has made the analysis and assessment of national critical component of international portfolio management in recent years. We construct the model from comparing the relative SD of stock return whereby higher SDs are generally associated with more risk. This relative SD forms a principle component in the change of the weights on the international portfolio choice. The result shows that event jump risk not only makes the investor's allocation more conservative overall, but also it can be compensated on BRICs event risk.