Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and Adverse Effects Associated With Raloxifene: Multiple Outcomes of Raloxifene Evaluation

OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2–3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI −0.5–4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100–582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8–1.1), gallbladder disease (RR 1.0; 95% CI 0.7–1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4–5.1), or endometrial cancer (RR 0.9; 95% CI 0.3–2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I
Effect of immobilization on skeletal muscle nicotinic cholinergic receptors in the rat

THE effect of 4 weeks of hind limb immobilization on nicotinic acetylcholinergic receptors (nAChRs) in the neuromuscular junction of the soleus (SOL) and tibialis anterior (TIB) muscles was studied in rats. Quantitative measurements of the receptors was performed using [3H]α-bungarotoxin ([3H]α-BTx) receptor autoradiography. Junctional and extrajunctional nAChRs were significantly increased in the SOL and TIB after 4 weeks immobilization. However, a significant decrease in fiber cross-sectional area was observed only in the SOL muscle. Remobilization for 4 weeks reversed the changes in cholinergic receptors and muscle fibers but not in bone. Our findings suggested that lack of nerve impulses are of importance for the events that take place after immobilization leading to muscle atrophy and osteoporosis.
Altered Cav1.2 function in the Timothy syndrome mouse model produces ascending serotonergic abnormalities

Polymorphism in the gene CACNA1C, encoding the pore‐forming subunit of Cav1.2 L‐type calcium channels, has one of the strongest genetic linkages to schizophrenia, bipolar disorder and major depressive disorder: psychopathologies in which serotonin signaling has been implicated. Additionally, a gain‐of‐function mutation in CACNA1C is responsible for the neurodevelopmental disorder Timothy syndrome that presents with prominent behavioral features on the autism spectrum. Given an emerging role for serotonin in the etiology of autism spectrum disorders (ASD), we investigate the relationship between Cav1.2 and the ascending serotonin system in the Timothy syndrome type 2 (TS2‐neo) mouse, which displays behavioral features consistent with the core triad of ASD. We find that TS2‐neo mice exhibit enhanced serotonin tissue content and axon innervation of the dorsal striatum, as well as decreased serotonin turnover in the amygdala. These regionally specific alterations are accompanied by an enhanced active coping response during acute stress (forced swim), serotonin neuron Fos activity in the caudal dorsal raphe, and serotonin type 1A receptor‐dependent feedback inhibition of the rostral dorsal raphe nuclei. Collectively, these results suggest that the global gain‐of‐function Cav1.2 mutation associated with Timothy syndrome has pleiotropic effects on the ascending serotonin system including neuroanatomical changes, regional differences in forebrain serotonin metabolism and feedback regulatory control mechanisms within the dorsal raphe. Altered activity of the ascending serotonin system continues to emerge as a common neural signature across several ASD mouse models, and the capacity for Cav1.2 L‐type calcium channels to impact both serotonin structure and function has important implications for several neuropsychiatric conditions.
IgA Antibodies Impair Resistance against Helicobacter pylori Infection: Studies on Immune Evasion in IL-10-Deficient Mice1

We recently reported that Helicobacter pylori-specific Abs impair the development of gastritis and down-regulate resistance against H. pylori infection. In this study, we asked whether IgA Abs specifically can have an impact on H. pylori colonization and gastric inflammation. To obtain a sensitive model for the study of inflammation we crossed IgA- and IL-10-deficient mice. We found that IL-10−/−/IgA−/− mice were significantly less colonized than IL-10−/−/IgA+/+ mice, which in turn were less colonized than wild-type (WT) mice. The IL-10−/−/IgA−/− mice exhibited a 1.2-log reduction in bacterial counts compared with that in IL-10−/−/IgA+/+ mice, suggesting that IgA Abs rather promoted than prevented infection. The reduced colonization in IL-10−/−/IgA−/− mice was associated with the most severe gastritis observed, albeit all IL-10−/− mice demonstrated more severe gastric inflammation than wild-type mice. The gastritis score and the infiltration of CD4+ T cells into the gastric mucosa were significantly higher in IL-10−/−/IgA−/− mice than in IL-10−/−/IgA+/+ mice, arguing that IgA Abs counteracted inflammation. Moreover, following oral immunization, IL-10−/−/IgA−/− mice were significantly better protected against colonization than IL-10−/−/IgA+/+ mice. However, the stronger protection was associated with more severe postimmunization gastritis and gastric infiltration of CD4+ T cells. There was also a clear increase in complement receptor-expressing cells in IL-10−/−/IgA−/− mice, though C3b-fragment deposition in the gastric mucosa was comparable between the two. Finally, specific T cell responses to recall Ag demonstrated higher levels of IFN-γ production in IL-10−/−/IgA−/− as compared with IL-10−/−/IgA+/+ mice. Thus, it appears that IgA and IL-10 help H. pylori bacteria evade host resistance against infection.
Curious Partnership in Global Imbalances: China’s Continual Accumulation of US Treasuries

The combination of American excess consumption and China’s financial extravaganza in accumulating US treasuries has been widely perceived as a major contributor to global imbalances. The current research examines whether this curious partnership can be sustained by concentrating on the Chinese side of the story, i.e. to what extent China may continue to accumulate US treasuries. Evidence from our model simulation and analysis suggests that the inertia effect is the most powerful influence driving the continuation of the stockpiling. As a result of influences from behavioural factors and internal governance elements, China’s American treasury holdings are now so large that the management of this colossal wealth has assumed its own life and dynamics. As a result, at least in the short run there shall be no sudden stop to China’s continual accumulation of American assets. In the longer run, interest rates and productivity improvement in China and around the world play a lasting role. It is unlikely that changes in US consumer behaviour will be able to fundamentally change China’s hoarding. Neither is there evidence that Renminbi exchange rate changes will impact on China’s willingness to hold its stock of American assets. These findings mean that even if the inertia effect is controlled, transformation of the curious partnership would require China to keep a very low interest rate for a fairly long period, and the US to adopt a substantially high interest rate. Moreover, there would have to be large and sustainable improvements in productivity in both China and the US. We have no reason to expect that these changes will be forthcoming, and so the party will go on. The bizarre partnership between China and America will be a lasting feature of the world economy.
Starting technologically innovative ventures: reasons, human capital, and gender

Purpose – Given the importance of technology in competitive advantage, this paper seeks to better understand the factors associated with entrepreneurs' decision to incorporate innovative technologies in new ventures. It aims to explore three questions: “Are the reasons given for starting technologically innovative new ventures (TINVs) different from those given for starting ventures based on traditional technologies? ”; “What is the role of human capital in the TINV startup decision? ”; and “Do gender differences exist in the reasons and human capital associated with starting a TINV? ”. Design/methodology/approach – Data were obtained from the Panel Study of Entrepreneurial Dynamics II (PSED II), which is a national database of individuals in various stages of starting a business. The overall sample consisted of 950 individuals. Non‐parametric methods and logistic regressions were used to test hypotheses.Findings – Results show that men start the TINV for self‐realization reasons, and that wealth seeking and .
Mechanisms of GABA‐ and Glycine‐Induced Increases of Cytosolic Ca2+ Concentrations in Chick Embryo Ciliary Ganglion Cells

Abstract: We used fura‐2 microfluorometry and the gramicidin‐perforated patch clamp technique in an attempt to clarify the mechanisms underlying the GABA‐and glycine‐induced increases in the cytosolic Ca2+ concentration ([Ca]in) in acutely isolated chick embryo ciliary ganglion neurons. GABA, glycine, and isoguvacine, but not baclofen, increased [Ca]in in a dose‐ and a Ca2+‐dependent manner. The GABA‐induced [Ca]in increase was inhibited by bicuculline and picrotoxin, and potentiated by pentobarbital, flunitrazepam, and alphaxalone, whereas the glycine‐induced [Ca]in increase was inhibited by strychnine but not by bicuculline or picrotoxin. L‐and N‐type Ca2+ channel blockers inhibited the GABA‐and glycine‐induced [Ca]in increases, whereas Bay K‐8644 potentiated these responses. These responses were also substantially potentiated by blockers of various K+ channels and by lowering the external Cl− concentrations. The high KCI‐ and nicotine‐induced [Ca]in increases were substantially reduced during continuous stimulation with either 2 µM GABA or 1 mM glycine. Electrophysiological studies indicated that the reversal potential of the GABA‐induced current exhibited a more depolarized value than the resting membrane potential in 17 of the 25 cells examined. Taken together, these results suggest that both GABA and glycine depolarize the membrane potentials by increasing Cl− conductance via respective receptors and thus increase the Ca2+ influxes through L‐ and N‐type voltage‐dependent Ca2+ channels.
Comparative effects of green and black tea extracts on lowering serum uric acid in hyperuricemic mice

Abstract Context: Tea (Camellia sinensis (L.) Kuntze [Theaceae]) is used to induce urination and inducing nervous excitation. Green and black teas have multifarious physiological functions. The different effects of green and black tea aqueous extracts (GTEs and BTEs) on hyperuricemia are not definitely reported. Objective: The different effects of GTEs and BTEs on lowering serum uric acid (UA) in hyperuricemic mice were determined. Materials and methods: Kunming mice were divided into nine groups (n = 6/each group). GTEs and BTEs at the doses of 0.5, 1 and 2 g/kg were orally administrated to mice for seven days, respectively. Hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) activities as mechanisms of actions were assessed. Results: Research indicated that the LD50 of tea extract is greater than 2 g/kg in mice. UA levels were suppressed significantly with dose-dependent treatment of 0.5, 1 and 2 g/kg BTEs (up to 25.5%, 28.7% and 29.8%, respectively); the serum UA levels were decreased by GTEs but not significant. The activities of XOD and ADA in high dose (2 g/kg) groups of both GTEs and BTEs were notably lower than those of the model group. Discussion and conclusions: The results suggested that both GTEs and BTEs have hypouricaemic and renal protective effects on hyperuricemic mice and the latter one was better. Our study sheds light on the research and development of anti-hyperuricemic functional foods and drugs from tea.
From here to eternity?: The practice of knowledge transfer in dispersed and co-located project organizations

This paper extends theoretical and empirical debates on knowledge transfer practices in geographically dispersed project teams using a range of communications media. It presents quantitative data comparing work interactions between dispersed and co-located teams in five international, project-based firms. It shows that contrary to conventional wisdom, their respective practices are similar for many work activities such as search and routine information exchange. However dispersed team members validate, verify and consult differently to the respective co-located teams. Qualitative data from interviews and observation then illustrates typical interactions using the differing means and media available to the observed project teams, such as task decomposition and emergency corrective work. Due to an unfortunate oversight one of the references in this article is incomplete. It can be found here.
Self�?Control Problems and Consumption�?Saving Decisions: Theory and Empirical Evidence

Time‐discounting is a fundamental preference which affects wealth accumulation. If people are impatient, they may spend their earnings instantaneously, and do not save enough for the future. People are often time‐inconsistent, i.e., they often put exceptionally high value on immediate consumption compared to any time in the future. Whether they are aware or not, these individuals are susceptible to self‐control problems. In this paper, we review theoretical and empirical research on time‐inconsistency and self‐control problems, particularly on consumption and saving, and discuss their policy implications.
Capacitance calculation of IC packages using the finite element method and planes of symmetry

Finite element techniques are presented for determining the capacitance of three-dimensional interconnection structures. Results are presented for two typical intergrated circuits packages: the plastic leaded chip carrier (PLCC) and the dual in-line package (DIP). The symmetry of the capacitance matrix in the package is described and a set of formulas is presented to take advantage of this symmetry in capacitance calculation. This leads to the reduction in CPU time and memory usage and better converged solution. >
Poverty and Inequality in a Rapid Growth Economy: Chile 1990-96

Using parametric and non-parametric methods this article examines the evolution of poverty and inequality in Chile between 1990 and 1996. This period is interesting because of the rapid growth exhibited by the Chilean economy. Using the Datt-Ravallion decomposition economic growth accounts for over 85 per cent of poverty reduction. The evidence suggests that the sustained level of high inequality is not necessarily associated with a lower welfare level. By comparing the evolution of poverty and inequality over time, we observe a continuous decrease in poverty, while inequality remains stable. This pattern has left everyone (both poor and rich individuals) better off.
La résilience face à la normativité et la solidarité des territoires. (Dés)Intégration du concept de résilience dans le Plan de Prévention des Risques d’Inondations du Val de Tours

Le maintien et le developpement des poles urbains en zone inondable questionnent l’efficacite des politiques de prevention des risques basees sur la maitrise de l’urbanisation. L’article analyse la resilience urbaine des representations gestionnaires du risque dans les Plans de Prevention des Risques (PPR) du Val de Tours – Val de Luynes. Le concept de resilience revele neanmoins les obstacles a son integration dans la reglementation des zones inondables. D’une part, l’unicite de la norme dans l’application des PPR evacue toute possibilite de prise en compte de la resilience. D’autre part, la capacite d’adaptation et d’auto-organisation des habitants est une condition necessaire afin d’assurer la perennite d’une societe face a une perturbation. Loin d’inciter a des pratiques de cooperation et de solidarite, les changements de paradigme et d’echelle induits par la resilience se heurtent au manque de confiance entre les pouvoirs publics et la population.
An approach for wireless sensor networks topology control in indoor scenarios

This work presents a new approach for topology control (TC) in wireless sensor networks (WSN) devised for indoor scenarios with obstacles and no feedback mechanisms. The technique is supported by two novel metrics, namely Blockage Rate and Useful Area Rate, applicable to environments with well-defined obstacles described by Site Specific Propagation models. Simulation results in some realistic scenarios showed that the technique allows to relate connectivity with transmission power levels and to identify critical transmission power levels. Also, it is shown that the technique is equivalent to an approximated mean value in terms of connectivity aspects.
National-Level Determinants of Global Music Piracy and Online Music Sales: An Exploratory Study

Piracy adversely affects online music sales. This article aims to investigate the factors that affect global music piracy directly and electronic business indirectly. These factors can be grouped into three categories: economic, legal/regulatory, and technological. On analyzing data from 68 countries, a country’s economic status and regulatory status emerge as the primary factors affecting music piracy. Technology indirectly affects music piracy by acting as a mediator between a nation’s economic status and the music piracy rate. Hence, a nation can reduce its music piracy rate and enhance e-business by devising stricter laws to safeguard intellectual property, punishing violations of information and communication technology related laws more strictly, allowing more free trade with other countries, inspiring attitudinal changes about inappropriate copying behavior through awareness campaigns, and encouraging increased and secure broadband usage.
Tax Subsidies for R&D in Canadian Provinces

In Canada there is too much focus on who is accountable to whom? or who controls what? and not enough on who is accountable for what? The federal government must lead consensus building toward an action plan regarding what works best in the delivery of mental health and addictions services - and the provinces must take seriously the implementation of a national plan that cultivates a culture of partnership and continuous improvement. Some redefinition of roles may have to be negotiated, but regional health authorities have to coordinate with national and provincial frameworks.
Detection of Tax-specific CTLs in lymph nodes of adult T-cell leukemia/lymphoma patients and its association with Foxp3 positivity of regulatory T-cell function

Human T-cell lymphotropic virus type (HTLV)-1 Tax is a viral protein that has been reported to be important in the proliferation of adult T-cell leukemia/lymphoma (ATLL) cells and to be a target of HTLV-1-specific cytotoxic T lymphocytes (CTLs). However, it is not clear how Tax-specific CTLs behave in lymph nodes of ATLL patients. The present study analyzed the immunostaining of Tax-specific CTLs. Furthermore, ATLL tumor cells are known to be positive for forkhead box P3 (Foxp3)and to have a regulatory T (Treg)-cell-like function. The association between T-reg function and number and activity of Tax-specific CTLs was also investigated. A total of 15 ATLL lymphoma cases with human leukocyte antigen (HLA)-A24, for which Tax has a high affinity, were selected from the files of the Department of Pathology, School of Medicine, Kurume University (Kurume, Japan) using a polymerase chain reaction (PCR) method. Immunostaining was performed for cluster of differentiation (CD) 20, CD3, CD4, CD8, T-cell intracellular antigen-1 and Foxp3 in paraffin sections, and for Tax, interferon γ and HLA-A24 in frozen sections. In addition, the staining of Tax-specific CTLs (HLA-A24-restricted) was analyzed by MHC Dextramer® assay in frozen sections. In addition, the messenger RNA expression of Tax and HTLV-1 basic leucine zipper factor were also evaluated by reverse transcription-PCR. Immunohistochemical staining of Tax protein in lymphoma tissue revealed the presence of positive lymphoma cells ranging from 5 to 80%, and immunohistochemical staining of HLA-A24 revealed the presence of positive lymphoma cells ranging from 1 to 95%. The expression of Tax and HLA-A24 was downregulated by viral function. Foxp3, a marker for Treg cells, was expressed in 0–90% of cells. Several cases exhibited Tax-specific CTL (HLA-A24-restricted)-positive cells, and there was an inverse correlation between Tax-specific CTLs and Foxp3. However, neither Tax nor HLA-A24 expression was associated with CTL or Foxp3. Our study indicated the possibility that ATLL cells, which expressed Tax, target of CTL, evade the CTL-mediated immune control by expression of Foxp3 as a Treg function.
CEO Overconfidence and Long‐Term Performance Following R&D Increases

type="main"> We examine the relation between Chief Executive Officer (CEO) overconfidence and significant increases in research and development (R&D) expenditures. Although prior studies reveal a significantly positive market reaction to increases in R&D expenditures in both the long and short run, we find that long-run stock performance is positive only for firms whose CEOs are not overconfident. Our findings, which may be attributable to overinvestment and the overestimation of future cash flows, imply that R&D resulting from overconfident behavior does not provide any value to firms.
A fast-lock synchronous multi-phase clock generator based on a time-to-digital converter

An all-digital fast-lock synchronous multi-phase clock generator is presented. By using a time-to-digital converter for fast-lock operation and delay measurement, the proposed multi-phase clock generator generates four-phase clocks and synchronizes the reference clock with the output clock within 45 cycles. Furthermore, the clock generator uses a fine binary scheme and de-skewing circuit for fine delay measurement and compensation. The proposed clock generator was designed in a 0.18um CMOS technology. It operates over a wide frequency range from 400MHz to 1.22GHz and consumes 34mW at 1.22GHz.
A Positive Economic Theory of Regulatory Enforcement

A positive economic model of regulatory enforcement is developed th at allows the agency to use both legal and informal methods to gain compliance with the law. The paper fills a gap in the economic literature on regulation by developing and testing a model of enforcement. It also provides a theoretical framework for the recent empirical work of political scientists and sociologists on enforcement practices. Copyright 1988 by Royal Economic Society.