Miracle-dz/UniFAR-FTUs huggingface dataset:
β3-Adrenergic Stimulation Differentially Inhibits Insulin Signaling and Decreases Insulin-induced Glucose Uptake in Brown Adipocytes*

Activity of the sympathetic nervous system is an important factor involved in the pathogenesis of insulin resistance and associated metabolic and vascular abnormalities. In this study, we investigate the molecular basis of cross-talk between β3-adrenergic and insulin signaling systems in mouse brown adipocytes immortalized by SV40 T infection. Insulin-induced tyrosine phosphorylation of the insulin receptor, insulin receptor substrate 1 (IRS-1), and IRS-2 was reduced by prestimulation of β3-adrenergic receptors (CL316243). Similarly, insulin-induced IRS-1-associated and phosphotyrosine-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity, but not IRS-2-associated PI 3-kinase activity, was reduced by β3-adrenergic prestimulation. Furthermore, insulin-stimulated activation of Akt, but not mitogen-activated protein kinase, was diminished. Insulin-induced glucose uptake was completely inhibited by β3-adrenergic prestimulation. These effects appear to be protein kinase A-dependent. Furthermore inhibition of protein kinase C restored the β3-receptor-mediated reductions in insulin-induced IRS-1 tyrosine phosphorylation and IRS-1-associated PI 3-kinase activity. Together, these findings indicate cross-talk between adrenergic and insulin signaling pathways. This interaction is protein kinase A-dependent and, at least in part, protein kinase C-dependent, and could play an important role in the pathogenesis of insulin resistance associated with sympathetic overactivity and regulation of brown fat metabolism.
The optimal top marginal tax rate: Application to Hungary

The paper applies recent developments in the theory of optimal income taxation to the Hungarian personal income tax system. The main conclusion is that the optimal top marginal tax rate in Hungary is likely to be higher, perhaps substantially, than the actual rate. It is discussed how this result depends on the parameters describing labor-supply behavior, the income distribution, and the redistributive preferences of society.
God Save Ulster!: The Religion and Politics of Paisleyism

This unique insight into Unionist politics and religion in Northern Ireland centres on the enigmatic and charismatic qualities of the Rev Ian Paisley, the only modern Western leader to have founded his own Church, the Free Presbyterian Church of Ulster, and his own political party, the Democratic Unionist Party. In this first serious study of Paisley's dual career, Dr Bruce analyses his enduring popularity and success, which mirror the complex issues continuing to plague the province.
Mechanisms Underlying Skeletal Muscle Weakness in Human Heart Failure: Alterations in Single Fiber Myosin Protein Content and Function

Background—Patients with chronic heart failure (HF) frequently experience skeletal muscle weakness that limits physical function. The mechanisms underlying muscle weakness, however, have not been clearly defined. Methods and Results—This study examined the hypothesis that HF promotes a loss of myosin protein from single skeletal muscle fibers, which in turn reduces contractile performance. Ten patients with chronic HF and 10 controls were studied. Muscle atrophy was not evident in patients, and groups displayed similar physical activity levels, suggesting that observed differences reflect the effects of HF and not muscle atrophy or disuse. In single muscle fibers, patients with HF showed reduced myosin heavy chain protein content (P<0.05) that manifested as a reduction in functional myosin-actin cross-bridges (P<0.05). No evidence was found for a generalized loss of myofilament protein, suggesting a selective loss of myosin. Accordingly, single muscle fiber maximal Ca2+-activated tension was reduced in myosin heavy chain I fibers in patients (P<0.05). However, tension was maintained in myosin heavy chain IIA fibers in patients because a greater proportion of available myosin heads were bound to actin during Ca2+ activation (P<0.01). Conclusions—Collectively, our results show that HF alters the quantity and functionality of the myosin molecule in skeletal muscle, leading to reduced tension in myosin heavy chain I fibers. Loss of single fiber myosin protein content represents a potential molecular mechanism underlying muscle weakness and exercise limitation in patients with HF.
The Association between Audit Committee Characteristics and Audit Fees

This study examines the association between audit committee characteristics and audit fees, using data gathered under the recent SEC fee disclosure rules. We hypothesize that audit fees will be positively associated with audit committee independence, financial expertise, and meeting frequency. We examine a sample of 492 nonregulated, Big 5‐audited firms that filed proxy statements with the SEC in the period from February 5, 2001 to June 30, 2001. We find that audit committee independence (defined as an audit committee comprised entirely of outside, independent directors) and financial expertise (defined as an audit committee containing at least one member with financial expertise) are significantly, positively associated with audit fees. This is in contrast to the findings of Carcello et al. (2002a), who find that audit committee characteristics are not significant in the presence of board‐related variables. Meeting frequency (defined as an audit committee that meets at least four times annually) was not .
Update on neuroimaging in epilepsy

Neuroimaging in epilepsy is a very large and growing field. Researchers in this area have quickly adopted new methods, resulting in a lively literature. Basic features of common epilepsies are well known, but, outside of the specific area of epilepsy surgery evaluation, new methods evolving in the last few years have had limited new beneficial clinical impact. Here, an overview of the epilepsy neuroimaging literature of the last 5 years, with an emphasis on mesial temporal lobe epilepsy, idiopathic generalized epilepsies, presurgical evaluation and new developments in functional MRI is presented. The need for attention to clinical translation, as well as immediate opportunities and future trends in this field, are discussed.
Constant disloyalty and the keys to community

Purpose – This paper aims to argue that trust and a sense of community are important in any organization, but increasingly complex structures and different cultures in large companies make it difficult to achieve a community. This, in turn, can harm trust, which is potentially damaging to business success.Design/methodology/approach – The paper demonstrates that different groups in an organization – the global group, matrixed middle and locally loyal – have different community needs. The costs and benefits of community for the three groups are also different. Each group faces its own challenges, but those in the middle group often have the greatest challenges as they constantly find themselves torn between central directives and local realities.Findings – The paper contends that, while community and trust correlate with lower costs, faster change, profitability and retention, in more extensive, distributed complex organizations the cost of building community is much higher and organizations therefore need.
Individual Entrepreneurial Intent: Construct Clarification and Development of an Internationally Reliable Metric

Individual entrepreneurial intent is a key construct in research on new business formation. However, neither a clear or consistent definition of nor a uniform and reliable way to measure individual entrepreneurial intent has yet emerged. Several management scholars have highlighted the impediment this constitutes to the advancement of entrepreneurship research. This paper first seeks to clarify the construct of individual entrepreneurial intent and then reports the development and validation of a reliable and internationally applicable individual entrepreneurial intent scale.
The Effect of Management Commitment To Service On Employee Service Behaviors: the Mediating Role of Job Satisfaction

This study focuses on the effect of four management-commitment-to-service factors (i.e., organizational support, rewards, empowerment, and training) on employees' job satisfaction and service behaviors. Ten hotels, located in Bangkok, the capital of Thailand, participated in this study. The structural equation model using Thai hotel workers indicated that rewards, empowerment, and training are positively related to job satisfaction but did not support a path from organizational support to job satisfaction. The positive impact of empowerment on employees' job satisfaction in a high-power-distance culture such as Thailand was an unexpected finding. It may result from proper training and reward systems offered to young Thai frontline employees who are familiar with and favor U.S. (Western) culture. Furthermore, job satisfaction was found to have a significant influence on Thai employees' extra-role customer service behaviors and cooperation. In summary, this study shows that job satisfaction serves as a mediator between three management service initiatives (rewards, empowerment, and training) and employees' service behaviors toward customers and coworkers.
Optimizing long-circulating liposomes for delivery of simvastatin to C26 colon carcinoma cells

Abstract Simvastatin (SIM) is a lipophilic statin that has potential benefits for prevention and treatment of several types of malignancies. However, its low water solubility and the toxicity associated with administration of high doses recommend it for encapsulation in carriers able to deliver the therapeutic dose in the tumor. In this work, liposomes with long-circulating properties were proposed as delivery systems for SIM. The objective of this study was to optimize the formulation of SIM-loaded long-circulating liposomes (LCL-SIM) by using D-optimal experimental design. The influence of phospholipids concentration, phospholipids to cholesterol molar ratio and SIM concentration was studied on SIM liposomal concentration, encapsulation efficiency and liposomal size. The optimized formulation had liposomal SIM concentration 6238 µg/ml, EE % of 83.4 % and vesicle size of 190.5 nm. Additionally we evaluated the in vitro cytotoxicity of the optimized liposomal SIM (LCL-SIM-OPT) on C26 murine colon carcinoma cells cultivated in monoculture as well as in co-culture with murine peritoneal macrophages at a cell density ratio that provides an approximation of physiological conditions of colon carcinoma development in vivo. Our preliminary studies suggested that LCL-SIM-OPT exerted cytotoxicity on C26 cells probably via enhancement of oxidative stress in co-culture environment.
Potassium and sodium ion current noise in the membrane of the squid giant axon.

1. The spectral density of current noise power from 20 mm segments of giant axons of the squid Loligo vulgaris has been measured under space‐clamp and voltage‐clamp conditions. From 4 to 1000 Hz the measured noise is larger by several orders of magnitude than the theoretical thermal noise. The amplifier's noise, which may yield appreciable contributions above 200 Hz, could be evaluated and subtracted from the total noise using direct measurements of the membrane impedance.
Earnings Management During Import Relief Investigations

This study tests whether firms that would benefit from import relief (e.g., tariff increases and quota reductions) attempt to decrease earnings through earnings management during import relief investigations by the United States International Trade Commission (ITC). The import relief determination made by the ITC is based on several factors that are specified in the federal trade acts, including the profitability of the industry. Explicit use of accounting numbers in import relief regulation provides incentives for managers to manage earnings in order to increase the likelihood of obtaining import relief and/or increase the amount of relief granted. While studies of earnings management typically examine situations in which all contracting parties have incentives to "perfectly" monitor (adjust) accounting numbers for such manipulation, import relief investigations provide a specific motive for earnings management that is not
Bifidobacterium Breve Enhances Transforming Growth Factor &bgr;1 Signaling by Regulating Smad7 Expression in Preterm Infants

Objectives: Transforming growth factor (TGF) &bgr;1 displays a broad spectrum of activities in mucosal regulation, including induction of oral tolerance, potent anti-inflammatory effects, mucosal IgA expression and effects on epithelial cell proliferation and differentiation. The present study examined the effect of probiotics on the immunologic system of preterm infants in relation to TGF-&bgr; signaling. Methods: Subjects comprised 19 preterm infants divided into 2 groups: receiving Bifidobacterium breve supplementation (B. breve group) and without supplementation (controls). Blood samples were collected from both groups on days 0, 14 and 28 after birth. Serum cytokine levels were measured using enzyme-linked immunosorbent assay, and expression levels of the TGF-&bgr; signaling molecule, Smad, were examined using semiquantitative reverse transcriptase-polymerase chain reaction. Results: Serum TGF-&bgr;1 level was elevated on day 14 and remained elevated on day 28 in the B. breve group. Level of messenger RNA expression was enhanced for Smad3 and reduced for Smad7 (antagonistic Smad) after B. breve administration relative to levels in controls on day 28. Conclusions: These results demonstrated that the administration of B. breve to preterm infants can up-regulate TGF-&bgr;1 signaling and may possibly be beneficial in attenuating inflammatory and allergic reactions in these infants.
Does Government Funding Alter Nonprofit Governance? Evidence from New York City Nonprofit Contractors

This paper explores the relationship between nonprofit board governance practices and government contracting. Monitoring by a board is one way a governmental agency can help to insure quality performance by its contractors. Agencies could thus use both their selection process and their post-contracting power to influence board practice. Using a new, rich data set on the nonprofit contractors of New York City, we test a series of hypotheses on the effects of government funding on board practices. We find that significant differences exist in board practices as a function of government funding levels, differences that mark a shift of focus or energy away from some activities, towards others. Trustees of nonprofits which receive high government funding are significantly less likely to engage in the traditional board functions, such as fund raising, while more likely to engage in financial monitoring and advocacy.
Effects of metformin on insulin secretion, insulin action, and ovarian steroidogenesis in women with polycystic ovary syndrome.

Hyperinsulinemia contributes to the ovarian androgen overproduction and glucose intolerance of polycystic ovary syndrome (PCOS). We sought to determine whether metformin would reduce insulin levels in obese, nondiabetic women with PCOS during a period of weight maintenance and thus attenuate the ovarian steroidogenic response to the GnRH agonist leuprolide. All subjects (n = 14) had an oral glucose tolerance test, a GnRH agonist (leuprolide) test, a frequently sampled iv glucose tolerance test, graded and oscillatory glucose infusions, and a dual energy x-ray absorptiometry scan before and after treatment with metformin (850 mg, orally, three times daily for 12 weeks). With weight maintenance (body mass index: pretreatment, 39.0 +/- 7.7 kg/m2, posttreatment, 39.1 +/- 7.9 kg/m2), oral glucose tolerance, insulin sensitivity (Si; 0.87 +/- 0.82 vs. 0.74 +/- 0.63 x 10(-5) min-1/ pmol.L), and the relationship between Si and first phase insulin secretion (AIRg vs. Si) were not improved by metformin. The insulin secretory response to glucose, administered in both graded and oscillatory fashions, was likewise unaltered in response to metformin. Free testosterone levels remained about 2-fold elevated (pretreatment, 26.6 +/- 12.7 pg/mL; posttreatment, 22.4 +/- 9.8 pg/mL). Both basal and stimulated LH and FSH levels were unaffected by metformin. The mean responses to leuprolide of 17-hydroxyprogesterone (pretreatment, 387 +/- 158 ng/dL; posttreatment, 329 +/- 116 ng/dL) as well as those of the other ovarian secretory products (androstenedione, dehydroepiandrosterone, progesterone, and estradiol) were not attenuated by metformin. We conclude that hyperinsulinemia and androgen excess in obese nondiabetic women with PCOS are not improved by the administration of metformin.
Promises and challenges for the implementation of computational medical imaging (radiomics) in oncology

Medical image processing and analysis (also known as Radiomics) is a rapidly growing discipline that maps digital medical images into quantitative data, with the end goal of generating imaging biomarkers as decision support tools for clinical practice. The use of imaging data from routine clinical work-up has tremendous potential in improving cancer care by heightening understanding of tumor biology and aiding in the implementation of precision medicine. As a noninvasive method of assessing the tumor and its microenvironment in their entirety, radiomics allows the evaluation and monitoring of tumor characteristics such as temporal and spatial heterogeneity. One can observe a rapid increase in the number of computational medical imaging publications-milestones that have highlighted the utility of imaging biomarkers in oncology. Nevertheless, the use of radiomics as clinical biomarkers still necessitates amelioration and standardization in order to achieve routine clinical adoption. This Review addresses the critical issues to ensure the proper development of radiomics as a biomarker and facilitate its implementation in clinical practice.
The Choice of Foreign Market Entry Modes: The Role of Resources and Industrial Driving Forces

The objective of the paper is to analyse the effects of corporate resources, attitudes of owner/entrepreneur/manager to internationalisation and the characteristics of the business industry on the entry mode choice. Based on factor and cluster analyses the authors highlight the latent structure lying behind different variables and find typical groups of companies matching the identified factors. Providing physical resources and access to appropriate information is necessary, but not sufficient. The attitude of the owner/entrepreneur/manager to internationalisation should be improved as well so that they will be able to appear and operate successfully in international markets. Giving the right place to subjective matters in promoting internationalisation may contribute to the increase in corporate participation in different support programs. On the basis of the obtained findings, different waysof how support programs can promote the companies’ international activities and strengthen their commitments to achieving higher added values can be defined.
Reluctant Entrepreneurs and their Clients The Case of Selfemployed Freelance Workers in the British Book Publishing Industry

JOHN STANWORTH IS DIRECTOR OF THE Future of Work Research Group at the London Management Centre, University of Westminster, England; Celia Stanworth is a researcher with the Future of Work Research Group and also a Senior Lecturer in Human Resource Management and Industrial Relations at Greenwich University Business School, England. The twin processes of large firm job loss and small firm job creation have traditionally been seen as essentially compartmentalised processes that is, jobs shed by large firms are seen as gone forever, while the jobs created by their small firm counterparts are seen in the opposite sense as completely new economic creations. However, the research reported here, drawn from the publishing industry in Britain, illustrates a more symbiotic relationship. It observes employers' changes in labour-use strategies, resulting in former in-house employees becoming externally located (homebased) and changing their employment status to 'freelance' selfemployed.
A Theory of Corporate Scope and Financial Structure

The authors simultaneously address three basic issues regarding the corporation: the optimal scope of operation, the optimal financial structure, and the relationship between these two. The starting point is that financial structure serves as a bonding device on the managers' self-interest behavior. The effectiveness of this bonding depends on the distribution of the firm's future cash flow, which in turn depends on the firm's scope. The authors' theory also links the firm's investment decisions to its operation scope. As empirical implications, the theory reconciles the failure of the 1960s U.S. conglomerates with the success of the Japanese keiretsu. Copyright 1996 by American Finance Association.
Safety of Withdrawing Inhaled Nitric Oxide Therapy in Persistent Pulmonary Hypertension of the Newborn

Objective. Because of case reports describing hypoxemia on withdrawal of inhaled nitric oxide (I-NO), we prospectively examined this safety issue in newborns with persistent pulmonary hypertension who were classified as treatment successes or failures during a course of I-NO therapy. Methods. Randomized, placebo-controlled, double-masked, dose-response clinical trial at 25 tertiary centers from April 1994 to June 1996. Change in oxygenation and outcome (death and/or extracorporeal membrane oxygenation) during or immediately after withdrawing I-NO were the principal endpoints. Patients (n = 155) were term infants, <3 days old at study entry with echocardiographic evidence of persistent pulmonary hypertension of the newborn. Exclusion criteria included previous surfactant treatment, high-frequency ventilation, or lung hypoplasia. Withdrawal from treatment gas (0, 5, 20, or 80 ppm) started once treatment success or failure criteria were met. Withdrawal of treatment gas occurred at 20% decrements at <4 hours between steps. Results. The patient profile was similar for placebo and I-NO groups. Treatment started at an oxygenation index (OI) of 25 ± 10 (mean ± SD) at 26 ± 18 hours after birth. For infants classified as treatment successes (mean duration of therapy = 88 hours, OI <10), decreases in the arterial partial pressure of oxygen (Pao 2) were observed only at the final step of withdrawal. On cessation from 1, 4, and 16 ppm, patients receiving I-NO demonstrated a dose-related reduction in Pao 2 (−11 ± 23, −28 ± 24, and −50 ± 48 mm Hg, respectively). For infants classified as treatment failures (mean duration of therapy = 10 hours), no change in OI occurred for the placebo group (−13 ± 36%, OI of 31 ± 11 after the withdrawal process); however a 42 ± 101% increase in OI to 46 ± 21 occurred for the pooled nitric oxide doses. One death was possibly related to withdrawal of I-NO. Conclusion. For infants classified as treatment successes, a dose response between the I-NO dose and decrease in Pao 2 after discontinuing I-NO was found. A reduction in I-NO to 1 ppm before discontinuation of the drug seems to minimize the decrease in Pao 2 seen. For infants failing treatment, discontinuation of I-NO could pose a life-threatening reduction in oxygenation should extracorporeal membrane oxygenation not be readily available or I-NO cannot be continued on transport.