Miracle-dz/UniFAR-FTUs huggingface dataset:
The V499G/Y501H Mutation Impairs Fast Motor Kinetics of Prestin and Has Significance for Defining Functional Independence of Individual Prestin Subunits*

Background: Prestin converts electrical energy into mechanical work. Results: The V499G/Y501H mutation significantly impairs fast motor kinetics of prestin. Conclusion: Impaired kinetics is attributable to mutation at the Val-499 site that is conserved among SLC26 proteins regardless of their function as motors or transporters. Significance: V499G/Y501H mutated prestin provides clues to the molecular mechanisms underlying somatic electromotility and thus cochlear amplification. Outer hair cells (OHCs) are a mammalian innovation for mechanically amplifying sound energy to overcome the viscous damping of the cochlear partition. Although the voltage-dependent OHC membrane motor, prestin, has been demonstrated to be essential for mammalian cochlear amplification, the molecular mechanism by which prestin converts electrical energy into mechanical displacement/force remains elusive. Identifying mutations that alter the motor function of prestin provides vital information for unraveling the energy transduction mechanism of prestin. We show that the V499G/Y501H mutation does not deprive prestin of its voltage-induced motor activity, but it does significantly impair the fast motor kinetics and voltage operating range. Furthermore, mutagenesis studies suggest that Val-499 is the primary site responsible for these changes. We also show that V499G/Y501H prestin forms heteromers with wild-type prestin and that the fast motor kinetics of wild-type prestin is not affected by heteromer formation with V499G/Y501H prestin. These results suggest that prestin subunits are individually functional within a given multimer.
Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism

Estrada G, Fatjó‐Vilas M, Muñoz MJ, Pulido G, Miñano MJ, Toledo E, Illa JM, Martín M, Miralles ML, Miret S, Campanera S, Bernabeu C, Navarro ME, Fañanás L. Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism.
Synergistic trans‐activation of the human C‐reactive protein promoter by transcription factor HNF‐1 binding at two distinct sites.

The promoter region of the human C‐reactive protein (CRP) gene comprises two distinct regions (APREs, for Acute Phase Responsive Elements) each one containing information necessary and sufficient for liver specific and IL‐6 inducible expression in human hepatoma Hep3B cells. In this paper we show that both APREs contain a low affinity binding site for the liver specific transcription factor HNF‐1/LF‐B1. The two sites are separated by approximately 80 bp. Mutations in either of the two sites abolish inducible expression. The same effect is specifically obtained in cotransfection competition experiments when the human albumin HNF‐1 site is used as competitor. However, HNF‐1 is not the intranuclear mediator of IL‐6 because synthetic promoters formed by multimerized copies of different HNF‐1 binding sites are not transcriptionally activated by this cytokine. An expression vector encoding full length HNF‐1 is capable of trans‐activating transcription from the wild‐type CRP promoter but not from mutants which have lost the ability to bind HNF‐1. Moreover, the level of trans‐activation observed with the natural promoter containing both HNF‐1 binding sites is far greater than the level of mutated variants containing only one of the two sites. This result strongly suggests that two HNF‐1 molecules bound simultaneously to sites distant from each other can act synergistically to activate gene expression.
The volume-regulated anion channel is formed by LRRC8 heteromers – molecular identification and roles in membrane transport and physiology

Abstract Cellular volume regulation is fundamental for numerous physiological processes. The volume-regulated anion channel, VRAC, plays a crucial role in regulatory volume decrease. This channel, which is ubiquitously expressed in vertebrates, has been vastly characterized by electrophysiological means. It opens upon cell swelling and conducts chloride and arguably organic osmolytes. VRAC has been proposed to be critically involved in various cellular and organismal functions, including cell proliferation and migration, apoptosis, transepithelial transport, swelling-induced exocytosis and intercellular communication. It may also play a role in pathological states like cancer and ischemia. Despite many efforts, the molecular identity of VRAC had remained elusive for decades, until the recent discovery of heteromers of LRRC8A with other LRRC8 family members as an essential VRAC component. This identification marks a starting point for studies on the structure-function relation, for molecular biological investigations of its cell biology and for re-evaluating the physiological roles of VRAC. This review recapitulates the identification of LRRC8 heteromers as VRAC components, depicts the similarities between LRRC8 proteins and pannexins, and discussed whether VRAC conducts larger osmolytes. Furthermore, proposed physiological functions of VRAC and the present knowledge about the physiological significance of LRRC8 proteins are summarized and collated.
Sprayable Microencapsulated Sex Pheromone Formulations for Mating Disruption of Four Tortricid Species: Effects of Application Height, Rate, Frequency, and Sticker Adjuvant

Abstract Several application parameters of microencapsulated (MEC) sex pheromone formulations were manipulated to determine their impact on efficacy of disruption for codling moth, Cydia pomonella (L.); oriental fruit moth, Grapholita molesta (Busck); obliquebanded leafroller, Choristoneura rosaceana (Harris); and redbanded leafroller, Argyrotaenia velutinana (Walker). Depending on the experiment, the formulations evaluated were those formerly manufactured by 3M Canada (London, ON, Canada) or those that are currently available from Suterra LLC (Bend, OR). The efficacy of MEC formulations applied by air-blast sprayer evenly throughout the entire canopy of 2–3-m-tall apple (Malus spp.) trees was equivalent to treatments in which targeted applications of MECs were made to the lower or upper 1.5 m of the canopy (at equivalent overall rates) for oriental fruit moth and both leafroller species. The realized distribution of deposited microcapsules within the tree canopy corresponded well with the intended heights of application within the canopy. The additional coapplication of the pine resin sticker Nu-Film 17 increased efficacy but not longevity of MEC formulations for oriental fruit moth; this adjuvant had no added effects for codling moth or leafroller formulations. Increasing the rate of active ingredient (AI) per hectare by 20–30-fold (range 2.5–75.0 g/ha) did not improve the disruption efficacy of MECs for codling moth or either leafroller species when both low and high rates were applied at equivalent frequencies per season. A low-rate, high-frequency (nine applications per season) application protocol was compared with a standard protocol in which two to three applications were made per season, once before each moth generation for each species. The low-rate, high-frequency protocol resulted in equivalent or better disruption efficacy for each moth species, despite using two-fold less total AI per hectare per season with the former treatment. The low-rate, frequent-application protocol should make the use of MEC formulations of synthetic pheromone more economical and perhaps more effective.
Analytical Description of Quasi-Random Magnetization Relaxation to Equilibrium

The Landau-Lifshitz (LL) dynamics of a uniformly magnetized particle is considered. The LL equation is written in the form of a Hamiltonian perturbed dynamical system. By using suitable averaging technique, the equation for the slow dynamics of the energy is derived. The averaging technique breaks up in the case of separatrix crossing. It is shown that, in the limit of small damping, the separatrix crossing can be described by using a probabilistic approach.
Financialization and Distribution from a Kaleckian Perspective: The United States, the United Kingdom, and Sweden Compared—Before and after the Crisis

Abstract In this article we analyze the effects of financialization on income distribution, before and after the Great Financial Crisis and the Great Recession, for the two liberal Anglo-Saxon economies, the United States and the United Kingdom, and for a typical Nordic welfare state economy, Sweden. We apply a Kaleckian perspective in which the focus will be on functional income distribution and thus on the relationship between financialization and the wage share or the gross profit share. According to this approach, financialization may affect aggregate wage or gross profit shares of the economy as a whole through three channels: first, the sectoral composition of the economy; second, the financial overhead costs and profit claims of the rentiers; and third, the bargaining power of workers and trade unions. We examine empirical indicators for each of these channels, both before and after the crisis. We find that the types of countries investigated here have shown broad similarities regarding redistribution before the crisis, however, with major differences in the underlying determinants. These differences have carried through to the period after the crisis and have led to different results regarding the development of distribution since then.
UK Renal Registry 11th Annual Report (December 2008): Chapter 9 Haemoglobin, ferritin and erythropoietin amongst patients receiving dialysis in the UK in 2007: national and centre-specifıc analyses

Background: The UK Renal Association (RA) and National Institute for Health and Clinical Excellence (NICE) have published Clinical Practice Guidelines which include recommendations for management of anaemia in established renal failure. Aims: To determine the extent to which the guidelines for anaemia management are met in the UK. Methods: Quarterly data (haemoglobin (Hb) and factors that influence Hb) extracts from renal centres in England, Wales and Northern Ireland (EWNI), and annual data from the Scottish Renal Registry for incident and prevalent renal replacement therapy (RRT) cohorts for 2007 were analysed by the UK Renal Registry (UKRR). Results: In the UK, in 2007 58% of patients commenced dialysis therapy with Hb ≥ 10.0 g/dl (median Hb 10.3 g/dl). Of incident patients 81% and 87% had a Hb ≥ 10.0 g/dl by 3 and 6 months of dialysis treatment respectively. The median Hb of haemodialysis (HD) patients was 11.6 g/dl with an interquartile range (IQR) of 10.6–12.6 g/dl. Of HD patients 86% had a Hb ≥ 10.0 g/dl. The median Hb of peritoneal dialysis (PD) patients in the UK was 11.9 g/dl (IQR 11.0–12.8 g/dl). 91% of UK PD patients had a Hb ≥ 10.0 g/dl. The median ferritin in HD patients in EWNI was 417 mg/L (IQR 270–598) and 95% of HD patients had a ferritin ≥ 100 mg/L. The median ferritin in PD patients was 255 mg/L (IQR 143–411) with 85% of PD patients having a ferritin ≥ 100 mg/L. In EWNI the mean ESA dose was higher for HD than PD patients (9,300 vs. 6,100 IU/week). Conclusions: This year for the first time there has been a small fall (from 85.9% in 2006 to 85.6%) in the percentage of HD patients with an Hb of ≥ 10 g/dl. This contrasts with previous annual improvements in this figure and is related to implementation of the new Hb Standard which has a target range of 10.5–12.5 g/dl.
DNA methylation epigenetically silences crossover hot spots and controls chromosomal domains of meiotic recombination in Arabidopsis

Yelina et al. show that RNA-directed DNA methylation is sufficient to locally silence Arabidopsis euchromatic crossover hot spots and is associated with increased nucleosome density and H3K9me2. This work demonstrates that DNA methylation plays a key role in establishing domains of meiotic recombination along chromosomes.
Magnesium in acute MI. Timing is critical.

It is an axiom of coronary care medicine that infarct size is a pivotal determinant of the prognosis of patients with acute myocardial infarction (AMI). When one is able to limit the size of an AMI, one is rewarded with a reduction in the number of potentially life-threatening complications such as pulmonary edema, cardiogenic shock, ventricular septal defects, papillary muscle rupture, and ventricular tachyarrhythmias.1 Salvage of even a rim of epicardial tissue as the wave front of necrosis spreads from the endocardium might prevent infarct expansion, ventricular remodeling, and congestive heart failure.2 3 Reperfusion that is sufficiently early (within 15 to 20 minutes) after AMI may prevent ischemic zones of myocardium from progressing to infarction. However, with the possible exceptions of an AMI that develops during cardiac catheterization, of patients who receive prehospital thrombolysis, or of the rare patient who occludes a coronary artery in the Emergency Department or coronary care unit and receives extraordinarily prompt and successful thrombolysis, reperfusion in cases of human AMI results in a mixture of necrotic and salvaged myocytes. The amount of myocardium that is irreversibly damaged (area of necrosis divided by area at risk) is directly related to the duration of occlusion. Interventions that delay cell death (eg, β-blockers) may help to protect ischemic myocytes and leave a greater quantity of viable cells that can subsequently be rescued by reperfusion. More than a decade ago, Braunwald and Kloner2 emphasized that reperfusion therapy, while beneficial in terms of myocardial salvage, may come at a cost because of a process referred to as reperfusion injury. Four aspects of reperfusion injury have been recognized4 : (1) lethal reperfusion injury (reperfusion-induced death of cells that were still viable at the moment of restoration of blood flow), (2) vascular reperfusion injury (no-reflow phenomenon and loss …
Green Entrepreneurship in Transitional Economies: Breaking Through the Constraints of Legitimacy

With environmental pollution, climate change and resource scarcity being serious global issues, green entrepreneurship is increasingly seen as an approach to simultaneously address economic performance, environmental impact and social responsibility. As green entrepreneurship needs to consider both venture performance and social responsibility, it will be subject to legitimacy constraints at the institutional level. Especially for transition economies in different countries, institutional uncertainty is a key factor. Better green performance can be easily achieved if green startups have a higher level of legitimacy. However, against the background of transitional economies, the increase in institutional uncertainty will damage the promotion of political legitimacy and make the enterprises subject to political legitimacy constraints lose their green performance. Overall startups in different industries need to develop green actions under the pressure of institutional constraints, and governments also need to improve policies and regulations quickly. Green Entrepreneurship in Transitional Economies: Breaking Through the Constraints of Legitimacy
Cardiovascular risk factors and low-back pain in a long-term follow-up of industrial employees.

OBJECTIVES Atherosclerosis of the lumbar vessels has been suggested as a mechanism leading to low-back pain (LBP). We studied whether seven cardiovascular disease (CVD) risk factors predict LBP. METHODS A sample (N=902) stratified by gender, age, and occupational class was drawn from employees in an engineering company in 1973 and examined for body mass index (BMI), smoking, exercise, serum total cholesterol and triglyceride concentrations, systolic blood pressure (SBP), diastolic blood pressure (DBP), and LBP. By November 2000, 232 persons had died, 108 from cardiovascular causes. In 2000, 546 (81% of the survivors) responded to a follow-up questionnaire on, for example, LBP. RESULTS Among the men, frequent local LBP at follow-up was predicted by high triglyceride and DBP levels and being a past smoker at baseline, adjusted for age, occupational class and frequent local LBP at baseline. In analogous models, high triglyceride and SBP levels and smoking (past and current) predicted frequent radiating LBP. An increased LBP score was predicted by a high BMI, serum total cholesterol, triglyceride, SBP and DBP levels, and smoking status at baseline. When BMI was allowed for, the associations between triglyceride level and all LBP outcomes persisted, as well as the association between SBP and frequent radiating LBP and an increased LBP score. An overall score of CVD risk factors showed a graded association with increased LBP. Among the women, a high BMI predicted frequent local and radiating LBP, and smoking at baseline predicted frequent radiating LBP and an increased LBP score. CONCLUSIONS The study adds to the evidence supporting the atherosclerosis-LBP hypothesis particularly for men.
Maternal serum granulocyte colony-stimulating factor levels and spontaneous preterm birth.

OBJECTIVE Preterm birth (PTB) remains a cause of substantial morbidity with an elusive etiology. Previous studies suggested an association of PTB with elevated serum levels of granulocyte colony-stimulating factor (G-CSF) at 28 weeks gestation. G-CSF, a hematopoietic cytokine, mediates the increase in leukocytes in pregnancy and may play a role in placentation. We evaluated the association between maternal serum G-CSF in the first and second trimesters and PTB. METHODS Serum samples collected for the Collaborative Perinatal Project (CPP) from women with normal pregnancy (n = 394) and PTB (n = 31), defined as delivery before 37 weeks gestation, were used to assess G-CSF levels. Linear regression was used to evaluate the relation of G-CSF with gestational age (GA) at birth. Logistic regression, conditional on GA at sample provision, was used to model the association between G-CSF and PTB. RESULTS G-CSF was significantly associated with gestational age at birth (p = 0.02). In conditional logistic regression models, G-CSF was significantly associated with PTB, with an adjusted odds ratio (AOR) of 1.52 (95% confidence interval [CI] 1.07, 2.16) per standard deviation (SD) increase. CONCLUSIONS Acute effects of G-CSF on PTB have been suggested. In our study we observed an association of higher serum G-CSF levels early in the second trimester with PTB, suggesting PTB as the culmination process beginning early in, if not before, pregnancy.
How does context affect interventions to improve patient safety? An assessment of evidence from studies of five patient safety practices and proposals for research

Background Logic and experience suggest that it is easier in some situations than in others to change behaviour and organisation to improve patient safety. Knowing which ‘context factors’ help and hinder implementation of different changes would help implementers, as well as managers, policy makers, regulators and purchasers of healthcare. It could help to judge the likely success of possible improvements, given the conditions that they have, and to decide which of these conditions could be modified to make implementation more effective. Methods The study presented in this paper examined research to discover any evidence reported about whether or how context factors influence the effectiveness of five patient safety interventions. Results The review found that, for these five diverse interventions, there was little strong evidence of the influence of different context factors. However, the research was not designed to investigate context influence. Conclusions The paper suggests that significant gaps in research exist and makes proposals for future research better to inform decision-making.
Hedging in a market with jumps - an FBSDE approach

We propose a model for hedging in a market with jumps for a large investor. The dynamics of the stock prices and the value process is governed by forward-backward SDEs driven by Teugels martingales. Unlike known FBSDE market models, ours accounts for jumps in stock prices. Moreover, it allows to find an optimal hedging strategy.
Increased Cdx protein dose effects upon axial patterning in transgenic lines of mice

To investigate the link between Cdx protein concentration and axial patterning in embryos, we made lines of mice OE1, OE2 and OE4 that overexpress each of the Cdx genes Cdx1, Cdx2 and Cdx4, respectively. The lines carry Cdx transgenes under the transcriptional control of their own promoter/enhancer elements. Transgenic embryos show Cdx transcription at 8.5 to 8.7 days within normal spatial domains for Cdx expression (primitive streak/tailbud), yet, overall, they contain elevated levels of Cdx proteins. Increased doses of Cdx proteins result in homeotic shifts in vertebral types along most of the vertebral column, with transformations being most obvious within the cervical region. Most of the shifts are anterior-to-posterior transformations and the anterior limits of these are commonly skull/vertebra 1 (v1) for OE1, v1/v2 for OE2 and v7 for OE4. OE embryos display anterior shifts in the expression of a Hoxa7/lacZ reporter within neural, paraxial and lateral plate mesoderm tissues. Hoxa7/lacZ expression commences at the normal time in OE1 and OE4 embryos. OE2 embryos display a forward shift in the gradient of Cdx2 protein along the axis, suggesting that a Cdx morphogen gradient model could account, at least in part, for the homeotic shifts in vertebral types. OE mice display additional defects: forelimb deficiencies in OE1, multiple tail axes, vertebral mis-alignments and axial truncations in OE2.
Subsequence Partition of Time Series Based on Different Width Time Window

Focusing on the limitation of traditional methods that the subsequences of time series are divided by the same width time window, an improved event series generation algorithm is proposed. Based on the improved event series generation algorithm, a new approach that divides the time series with different width time window is put forward. An example of time series division with different width time window is also presented in the paper.
Purchasing Power: The Gender and Class Imaginary on the Shopping Channel

STUDIES IN LANGUAGE AND GENDER Mary Bucholtz, General Editor Advisory Board Penelope Eckert, Stanford University Kira Hall, Yale University Janet Holmes, Victoria University of Wellington, New Zealand Miyako Inoue, Stanford University Don Kulick, University of Stockholm Sally McConnell—Ginet, Cornell University Marcyliena Morgan, University of California, Los Angeles/Harvard University Deborah Tannen, Georgetown University Ana Celia Zentella, Hunter College, City University of New York Reinventing Identities: The Gendered Self in Discourse Edited by Mary Bucholtz, A. C. Liang, and Laurel A. Sutton REINVENTING IDENTITIES The Gendered Self in Discourse Edited by Mary Bucholtz A. C. Liang Laurel A. Sutton New York Oxford OXFORD UNIVERSITY PRESS 1999
Guidance for Deliberative Monetary Valuation Studies

There is growing demand for more pluralistic valuation approaches, for which Deliberative Monetary Valuation (DMV) is suitable. Guidance is needed for valid and reliable DMV application, as exists for conventional willingness to pay studies using stated preference methods. The purpose of this paper is to develop a set of minimal requirements for study design and reporting aimed at DMV practitioners, based on the existing DMV literature as well as related social science literatures. The core contribution of our paper is the practical recommendations for DMV study design focusing on the deliberation process and elicitation format, analysis of the deliberation and willingness to pay results, and validity. We summarise reporting requirements for reliability, before offering conclusions and suggestions for promising future research directions.