Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiac ion channels.

The analysis of the molecular basis of the inherited cardiac arrhythmias has been the driving force behind the identification of the ion channels that generate the action potential. The genes encoding all the major ion channels have cloned and sequenced. The studies have revealed greater complexity than heretofore imagined. Many ion channels function as part of macromolecular complexes in which many components are assembled at specific sites within the membrane. This review describes the generation of the normal cardiac action potential. The properties of the major ionic currents are the examined in detail. Special emphasis is placed on the functional consequences of arrhythmia-associated ion channel mutations. The review concludes with a glimpse of the directions in which this new electrophysiology may lead. The normal sequence and synchronous contraction of the atria and ventricles require the rapid activation of groups of cardiac cells. An activation mechanism must enable rapid changes in heart rate and also respond to the changes in autonomic tone. The propagating cardiac action potential fulfils these roles. Figure 1 illustrates the 5 phases of the normal action potential: 1. Phase 4, or the resting potential, is stable at ≈−90 mV in normal working myocardial cells. 2. Phase 0 is the phase of rapid depolarization. The membrane potential shifts into positive voltage range. This phase is central to rapid propagation of the cardiac impulse (conduction velocity, θ=1 m/s). 3. Phase 1 is a phase of rapid repolarization. This phase sets the potential for the next phase of the action potential. 4. Phase 2, a plateau phase, is the longest phase. It is unique among excitable cells and marks the phase of calcium entry into the cell. 5. Phase 3 is the phase of rapid repolarization that restores the membrane potential to its resting value.1 Figure 1. Membrane currents that generate the a normal …
A General Causal Model to Guide Alcohol, Tobacco, and Illicit Drug Prevention: Assessing the Research Evidence

The problems associated with the use of alcohol, tobacco, and other drugs (ATOD) extract a significant health, social, and economic toll on American society. While the field of substance abuse prevention has made great strides during the past decade, two major challenges remain. First, the field has been disorganized and fragmented with respect to its research and prevention practices; that is, there are often separate ATOD prevention “specialists. ” Second, both the prevention researchers who test the efficacy of specific prevention strategies and the practitioners who implement prevention efforts often lack an overall perspective to guide strategy selection. To address these limitations, we present an ATOD causal model that seeks to identify those variables (Domains) that are theoretically salient and empirically connected across alcohol, tobacco, and illicit drugs. For the researcher, the model demonstrates important commonalities, as well as gaps, in the literature. For the practitioner, the model is a means to recognize both the complexity of the community system that produces ATOD problems and the multiple intervention points that are possible within this system. Researchers and practitioners are thus challenged to work synergistically to find effective and cost-effective approaches to change or reduce ATOD use and associated problems.
Assessing Fiscal Episodes

In an OCDE panel, for the period 1970-2010, we assess the effects of fiscal consolidation episodes, with four different definitions. Our results reveal that lower final government consumption would increase private consumption in three out of the four approaches, when there is a fiscal consolidation, and the debt ratio is above the cross-country average. The change in the cyclically adjusted primary balance and the duration of the consolidation episode contribute for the success of the consolidation, and the opposite applies if the latter is more based on the revenue side. Finally, the effects of social transfers on private investment tend to be negative.
Driver behaviour considerations in calibrating microsimulation models for capacity

Microscopic simulation (microsimulation) software is a powerful analytical tool that provides inexpensive and efficient analysis of real world traffic conditions. Thorough calibration is imperative for maintaining the reliability, accuracy and prediction power of microsimulation models. Defining roadway capacity is an important component of the calibration process. Microsimulators, such as VISSIM, contain user-defined input parameters which control the capacity of roadways. In previous studies, VISSIM freeway driver behaviour parameters have been shown to individually impact capacity. This paper analyses the interactive relationships between pairs of driver behaviour parameters and roadway capacity. Four interactive relationships were identified and scrutinised for this analysis of the dynamic relationship between simulated capacity and driver behaviour. A better understanding of these relationships will assist in the manual calibration of VISSIM microsimulation models and contribute to the development of automated calibration methodologies.
Individual Preferences, Monetary Gambles and the Equity Premium

We argue that narrow framing, whereby an agent who is offered a new gamble evaluates that gamble in isolation, separately from other risks she already faces, may be a more important feature of decision-making under risk than previously realized. To demonstrate this, we present evidence on typical attitudes to independent monetary gambles with both large and small stakes and show that across a wide range of utility functions, including all expected utility and many non-expected utility specifications, the only ones that can easily capture these attitudes are precisely those exhibiting narrow framing. Our analysis also makes predictions about the kinds of preferences that might be able to address the stock market participation and equity premium puzzles. We illustrate these predictions in simple portfolio choice and equilibrium settings.
Feature extraction and classification with wavelet transform and support vector machines

This paper introduces texture classification method by using wavelet transform and support vector machines. First, a wavelet-based texture feature set is obtained by the overcomplete wavelet decomposition of local areas in remote sensing images, then the texture classification is carried out by the SVM technique. The experiment results show that the method above discussed is admissible. KeywordsFeature extraction; texture classification; wavelet; support vector machines; neural networks
Characteristics of Chronic Pain Patients Who Take Opioids and Persistently Report High Pain Intensity

Background and Objectives The use of self-report questionnaires to detect characteristics of altered central pain processing, as seen in centralized pain disorders such as fibromyalgia, allow for the epidemiological studies of pain patients. Here, we assessed the relationship between reporting high levels of pain while taking opioids and the presence of characteristics associated with centralized pain. Methods We evaluated 582 patients taking opioid medications using validated measures of clinical pain, neuropathic pain symptoms, mood, and functioning. A multivariate linear regression model was used to assess the association between levels of pain while taking opioids and presenting with characteristics consistent with having centralized pain. Results We found that 49% of patients taking opioids continued to report severe pain (≥ 7/10). In multivariate analysis, factors associated with having higher levels of pain in opioid users included higher fibromyalgia survey scores (P = 0.001), more neuropathic pain symptoms (P < 0.001), and higher levels of depression (P = 0.002). Although only 3.2% were given a primary diagnosis of fibromyalgia by their physician, 40.8% met American College of Rheumatology survey criteria for fibromyalgia. Conclusions Our findings suggest that patients with persistently high pain scores despite opioid therapy are more likely than those with lower levels of pain to present with characteristics associated with having centralized pain. This study cannot determine whether these characteristics were present before (fibromyalgia-like patient) or after the initiation of opioids (opioid-induced hyperalgesia). Regardless, patients with a centralized pain phenotype are thought to be less responsive to opioids and may merit alternative approaches.
YeeV is an Escherichia coli toxin that inhibits cell division by targeting the cytoskeleton proteins, FtsZ and MreB

Toxin–antitoxin (TA) systems of free‐living bacteria have recently demonstrated that these toxins inhibit cell growth by targeting essential functions of cellular metabolism. Here we show that YeeV toxin inhibits cell division, leads to a change in morphology and lysis of Escherichia coli cells. YeeV interacts with two essential cytoskeleton proteins, FtsZ and MreB. Purified YeeV inhibits both the GTPase activity and the GTP‐dependent polymerization of FtsZ. YeeV also inhibits ATP‐dependent polymerization of MreB. Truncated C‐terminal deletions of YeeV result in elongation of cells, and a deletion of the first 15 amino acids from the N‐terminus of YeeV caused lemon‐shaped cell formation. The YeeV toxin is distinct from other well‐studied toxins: it directs the binding of two cytoskeletal proteins and inhibits FtsZ and MreB simultaneously.
Weak convergence of stochastic processes defined on semi-infinite time intervals

logues of these theorems for unbounded intervals are also valid. We shall confine our attention to the results of Skorohod [1], and in particular to those results concerning his J1 topology. Let E be a complete separable metric space with metric p. We denote by K the space of all E-valued functions x(t), 0O O
A Critical Assessment of Central Agency Motives in Danish Public Management Reform

This article explores the question why a relatively „healthy“ governance system like Denmark embarks on and continually develops NPM inspired public sector reforms. Expanding Roberts' categorization of problems as „simple“, „complex“ and „wicked“, the article interprets Hood's paradox of the „malade imaginaire“ as „solution driven problems“ in strong economies.
A Snapshot of Family Homelessness Across America

Homelessness remains one of the most misunderstood and least documented social policy issues of our time. For almost two decades, the majority of efforts to understand the issues surrounding homelessness have focused solely on transient men. Yet over the last fifteen years, the country has seen the rise of a new poverty: homeless families. Each year since 1993, the U.S. Conference of Mayors has reported that this group comprises the fastest growing segment of the homeless population.1 Today there are 400,000 homeless families in shelter, representing 1.1 million homeless children across America.2 Many Americans refuse to believe, however, that entire families are homeless in the richest country of the world. This collective denial has had grave consequences for homeless children and their families. The lack of hard data has not only obscured the complex nature of family homelessness, it has led to a crisis of policy in the dark. Policy prescriptions that are politically expedient have dominated public discourse. However, these policies are long on rhetoric and short on a reasoned appreciation for the myriad factors that contribute to and sustain family homelessness. In response to this gap between research and public policy, this study was designed to take a national snapshot of family homelessness: to describe the typical homeless family; to identify common trends in income, housing, educational and employment histories of homeless families across regions; and to es-
ALIANZA SUMMA: UNA APROXIMACIÓN DESDE LA TEORÍA DE LA ORGANIZACIÓN INDUSTRIAL

En este articulo, primero caracterizamos el mercado de transporte aereo comercial en Colombia y luego desarrollamos un modelo de reputacion que describe la relacion entre aerolineas y consumidores. Con base en el trabajo pionero de Grossman y Hart (1986) modelamos la integracion horizontal entre firmas, con posterior aplicacion al caso de la Alianza Summa. Por ultimo, consideramos los resultados y las posibles implicaciones de la Alianza Summa para la sociedad.
Thioredoxin induces Tregs to generate an immunotolerant tumor microenvironment in metastatic melanoma

Metastatic melanoma is a highly aggressive cancer that is very difficult to treat. Additionally, the antitumor immune reaction of melanoma is still unclear. Here we demonstrate an association between the expression and secretion of the antioxidant protein thioredoxin (TRX) and increasing tumor stage and metastasis in melanoma. To elucidate the role of TRX in melanoma, we assessed the correlation of TRX expression with different disease parameters in melanoma. We also examined the in vitro and in vivo effects of modulating TRX levels in melanoma cells using various methods of TRX depletion and augmentation. We further explored the effects of TRX on the cytokine milieu and the ability of TRX to regulate the proportion and specific activities of T-cell populations. We demonstrate that TRX expression correlates with Treg representation in clinical samples and, that modulation of TRX influences the induction of Tregs and the generation of an immunotolerant cytokine profile in mouse serum. Using a murine metastatic melanoma model, we identified a tumor immunoevasion mechanism whereby melanoma cell-secreted TRX enhances Treg infiltration. TRX displays chemotactic effects in recruiting Tregs, stimulates the conversion of conventional T cells to Tregs, and confers survival advantage to Tregs in the tumor microenvironment. In turn, this increase of Tregs generates immunotolerance in tissues and therefore decreases antitumor immune reactions. These results elucidate a mechanism by which TRX promotes metastatic melanoma in part through Treg recruitment to inhibit T-cell antitumor effects and suggest that TRX antibody may be useful in the clinic as a therapy against melanoma.
Which Should it Be Called: Convergent Validity or Discriminant Validity?

Correct and accurate use of terminology is essential to professional communications in any discipline. Recently, the use ofvalidity labels was discussed in Research Quarterly far Exercise and Sport (Sparling, Millard-Stafford, & Snow, 1998; Zhu, 1998)1. Zhu (1998) believed that the attempt made by Sparling and colleagues (Sparling, Millard-Stafford, & Snow, 1997) to correlate the Georgia Tech (GT) cadence curl-up test they developed with the AAHPERD I-min modified sit-up test and Robertson 1min curl-up test was not an effort to establish "concurrent validity," but rather "convergent validity. " Sparling et al. (1998) disagreed and argued that, because the correlations of the GT test and other sit-up/curl-up tests were not high, the findings should be called "divergent" validity (p. 3Ur. This disagreement raised an interesting question: How should convergent or divergent validity, which is more often called "discriminant validity" in the literature, be determined? Should it be determined by the magnitude ofcorrelation coefficients only or by something else? The purpose of this research note is to try to address these questions. It is hoped that the discussion will lead to a better understanding of these basic, but critical, concepts in test development and applications. To gain a better understanding of the difference between convergent and discriminant validity, a quick
The impact of service delivery quality on customer satisfaction in Indian banks

The banking sector has undergone many changes after liberalisation of the Indian economy and introduction of information technology in banking in India. The technology-related factors have changed the way the banking is done. Despite all these changes, it is the human touch and customer relationship which is responsible for enhancement of customer satisfaction, which is an important aspect of service delivery quality. This paper has examined the customer satisfaction from service delivery quality of leading Indian banks such as State Bank of India, ICICI Bank, HDFC Bank, and Punjab National Bank. The study surveys the opinion of 400 customers of two public-sector banks and two private-sector banks (100 from each bank). MANOVA and factor analysis have been used for having insights in the service delivery quality provided by the sample banks. The population studied here is urban population which can be considered as representative of banking customers in NCR Delhi.
Loss of phosphatase and tensin homolog or phosphoinositol-3 kinase activation and response to trastuzumab or lapatinib in human epidermal growth factor receptor 2-overexpressing locally advanced breast cancers.

PURPOSE Phosphatase and tensin homolog (PTEN) loss or activating mutations of phosphoinositol-3 (PI3) kinase (PIK3CA) may be associated with trastuzumab resistance. Trastuzumab, the humanized human epidermal growth factor receptor 2 (HER2) monoclonal antibody, and lapatinib, an epidermal growth factor receptor/HER2 tyrosine kinase inhibitor, are both established treatments for HER2-overexpressing breast cancers. Understanding of the cellular response to HER2-targeted therapies is needed to tailor treatments and to identify patients less likely to benefit. METHODS We evaluated the effect of trastuzumab or lapatinib in three HER2-overexpressing cell lines. We confirmed the in vitro observations in two neoadjuvant clinical trials in patients with HER2 overexpression; 35 patients received trastuzumab as a single agent for the first 3 weeks, then docetaxel every 3 weeks for 12 weeks (trastuzumab regimen), whereas 49 patients received lapatinib as a single agent for 6 weeks, followed by trastuzumab/docetaxel for 12 weeks before primary surgery (lapatinib regimen). Apoptosis, Ki67, p-MAPK, p-AKT, and PTEN were assessed by immunohistochemistry. Genomic DNA was sequenced for PIK3CA mutations. RESULTS Under low PTEN conditions, in vitro data indicate that lapatinib alone and in combination with trastuzumab was effective in decreasing p-MAPK and p-AKT levels, whereas trastuzumab was ineffective. In the clinical trials, we confirmed that low PTEN or activating mutation in PIK3CA conferred resistance to the trastuzumab regimen (P = .015), whereas low PTEN tumors were associated with a high pathologic complete response rate (P = .007). CONCLUSION Activation of PI3 kinase pathway is associated with trastuzumab resistance, whereas low PTEN predicted for response to lapatinib. These observations support clinical trials with the combination of both agents.
Metal-ion-mediated allosteric triggering of yeast pyruvate kinase. 1. A multidimensional kinetic linked-function analysis.

Regulation of the glycolytic pathway is considered to be primarily achieved by the carbon metabolites resulting from glucose metabolism [e.g., fructose 1,6-diphosphate (FDP), phosphoenolpyruvate (PEP), and citrate] and by the ATP charge of the cell. The divalent cations (e.g., Mg2+ and Mn2+) have not been considered as having regulatory roles in glycolysis, although they are involved in almost every enzyme-catalyzed reaction in the pathway. Using a kinetic linked-function analysis of steady-state kinetic data for the interactions of PEP, FDP, and Mn2+ with yeast pyruvate kinase (YPK), we have found that the divalent metal is the principal trigger of the allosteric responses observed with this enzyme. The interaction of Mn2+ to YPK enhances the interaction of FDP by -1.6 kcal/mol and the interaction of PEP by -2.8 kcal/mol. The simultaneous interaction of all three of these ligands to YPK is favored by -4.3 kcal/mol over the sum of their independent binding free energies. Surprisingly, the binding of the allosteric activator FDP does not directly influence the binding of the substrate PEP since a coupling free energy near zero was calculated for these two ligands. Thus, communication between the PEP and FDP sites occurs structurally through the metal by an allosteric relay mechanism. These conclusions are supported by results of a thermodynamic linked-function analysis of direct binding data for the interactions of PEP, FDP, and Mn2+ with YPK [Mesecar, A. D. , & Nowak, T. (1997) Biochemistry (following paper in this series)]. Our findings raise important questions as to the possible roles of divalent metals in modulating multiligand interactions with YPK and in the regulation of the glycolytic pathway.
Parties in the Council?

Ideology is widely seen as a powerful explanatory force of behaviour in collective decision-making. Yet, research on the Council of the European Union, the chief legislative body in the European Union, has only recently started to pay attention to ideology. We investigate to what extent formal position-taking can be explained by the ideological party affiliation of the governing parties. The focus is twofold. First, can aggregated coalition patterns be explained by ideological party affiliation? Second, do countries change coalition partners when there is a change of parties in government?
Employee work values and organizational attachment in North Mexican maquiladoras

Maquiladoras in Northern Mexico are currently plagued by low organizational attachment among production workers. Workers often feel little psychological commitment to their maquiladora, and turnover rates in the plants average about 10 per cent per month. In this study we examine the role that work values play in maquiladora workers' attachment to their organizations. An analysis of data from 227 production workers in two maquiladoras reveals that the upward-striving value (a desire continually to seek a higher-level job) is positively associated with turnover intentions and negatively associated with organizational commitment, while the social-status-of-job value (the perception that a good job merits respect) is positively associated with organizational commitment. The findings offer guidance to managers and management scholars attempting to understand and combat the organizational attachment problem in Northern Mexico.
The Use of Credit Ratings in Investment Management in the U.S. and Europe

We analyse a survey of 200 plan sponsors and investment managers in the US and Europe regarding the use of credit rating guidelines in the conduct of their investment activities. We find that ratings-based guidelines are widespread, but their forms and motivations vary considerably. The usage of ratings appears remarkably similar in the US and Europe. The adoption of ratings-based investment guidelines appears driven by the private sector, with regulation playing a relatively minor role. Guidelines generally reference ratings of specific agencies, rather than the ratings of all officially “recognized” agencies. Ratings-based guidelines seem unlikely to destabilize markets because although asset retention guidelines are common, rapid forced selling upon downgrades is not. Market participants express a preference on the margin for more accuracy over more stability, but stability is valued and guidelines rarely include agency outlook designations, which could be used to increase rating accuracy. These findings generally support the hypothesis presented in Cantor [2004] that ratings are used as governance tools by market participants to ameliorate principal-agent problems between asset managers and their clients.