Miracle-dz/UniFAR-FTUs huggingface dataset:
p160ROCK mediates RhoA activation of Na–H exchange

The ubiquitously expressed Na–H exchanger, NHE1, acts downstream of RhoA in a pathway regulating focal adhesion and actin stress fiber formation. p160ROCK, a serine/threonine protein kinase, is a direct RhoA target mediating RhoA‐induced assembly of focal adhesions and stress fibers. Here, stress fiber formation induced by p160ROCK was inhibited by the addition of a specific NHE1 inhibitor, ethylisopropylamiloride, in CCL39 fibroblasts, and was absent in PS120 mutant fibroblasts lacking NHE1. In CCL39 cells, NHE1 activity was stimulated by expression of mutationally active p160ROCK, but not by mutationally active protein kinase N, another RhoA target kinase. Expression of a dominant interfering p160ROCK inhibited RhoA‐, but not Cdc42‐ or Rac‐activation of NEH1. In addition, the p160ROCK‐specific inhibitor Y‐27632 inhibited increases in NHE1 activity in response to RhoA, and to lysophosphatidic acid (LPA), which stimulates RhoA, and it also inhibited LPA‐increased phosphorylation of NHE1. A C‐terminal truncation of NHE1 abolished both LPA‐induced phosphorylation and activation of the exchanger. Furthermore, mutationally active p160ROCK phosphorylated an NHE1 C‐terminal fusion protein in vitro, and this was inhibited in the presence of Y‐27632. Phosphopeptide maps indicated that identical residues in NHE1 were phosphorylated by p160ROCK in vivo and in vitro. These findings identify p160ROCK as an upstream, possibly direct, activator of NHE1, and suggest that NHE1 activity and phosphorylation are necessary for actin stress fiber asssembly induced by p160ROCK.
Media Coverage and the Cost of Debt

This paper investigates the relation between media coverage and offering yield spreads using a comprehensive dataset of 5,338 industrial bonds issued from 1990 to 2011. We find that media coverage is negatively associated with firms’ cost of debt. This association is robust to controlling for standard yield determinants, different model specifications, and endogeneity. We identify 4 economic channels through which media coverage influences the cost of debt: Information asymmetry, governance, liquidity, and default risk. Importantly, media coverage has an independent influence beyond the effects of these economic mechanisms and is not a proxy for other firm attributes.
Connecting Strategies to Resources: Scale Development of a Resource Bundle for Internet Retailing

Abstract Service strategy literature emphasizes the alignment of target market, service concept, and service delivery system. This article reports scale development of a resource bundle that is useful to implement service strategies in Internet retailing. Three dimensions of the resource bundle are proposed in this study. They cover three alignment parts between target market and service concept, service concept and service delivery system, and target market and service delivery system. To rigorously develop the measurement scale, this study uses a two-stage procedure which comprises an item-level study that uses judges and a scale-level study that employs a survey of Internet retailers. Finally, a second-order measurement model of the resource bundle with a total of 14 measurement items was established. Results of the confirmatory factor analysis reveal empirical evidence of resource complementarities, thereby providing critical information about desirable resource allocation for Internet commerce and, in turn, carrying some managerial implications.
Value of MRI in diagnostics and evaluation of myositis

Purpose of reviewThis review aims at covering the role of muscle MRI in supporting the diagnosis of myositis, in aiding to differentiate it from other muscle disorders, and in monitoring myositis patients over time by assessing response to treatment and by discriminating between muscle inflammation and chronic damage. Recent findingsMRI can assist in ‘pattern recognition’ of muscle involvement across numerous myopathies, including myositis. Novel applications of magnetic resonance such as cardiac MRI, MR elastography and blood oxigenation level-dependent magnetic resonance can shed light on different aspects of myositis and usefully complement conventional MRI in assessing patients with myositis. SummaryMRI can guide therapy by determining whether muscle weakness is related to edema (active inflammation) or muscle atrophy/fat replacement (chronic damage). There is a need to better standardize the assessment of MRI findings in myositis to provide defined outcome measures for use in clinical trials. Video abstracthttp://links.lww. com/COR/A36
Neonatal hyperthyrotropinemia: population characteristics, diagnosis, management and outcome after cessation of therapy

Introduction Neonatal hyperthyrotropinaemia (HT), defined by elevated TSH and normal T4, is either transient or persistent. The eventual outcome of neonatal HT is unpredictable and the management of HT patients is controversial. We assessed perinatal parameters and diagnostic measures that may distinguish between transient and persistent HT, compared with congenital hypothyroidism (CH). We also aimed to recommend optimal treatment in these forms of thyroid impairment.
Observer reliability of the Gross Motor Performance Measure and the Quality of Upper Extremity Skills Test, based on video recordings

The aim of this study was to examine observer reliability of the Gross Motor Performance Measure (GMPM) and the Quality of Upper Extremity Skills Test (QUEST) based on video clips. The tests were administered to 26 children with cerebral palsy (CP; 14 males, 12 females; range 2–13y, mean 7y 6mo), 24 with spastic CP, and two with dyskinesia. Respectively, five, six, five, four, and six children were classified in Gross Motor Function Classification System Levels I to V; and four, nine, five, five, and three children were classified in Manual Ability Classification System levels I to V. The children's performances were recorded and edited. Two experienced paediatric physical therapists assessed the children from watching the video clips. Intraobserver and interobserver reliability values of the total scores were mostly high, intraclass correlation coefficient (ICC)1,1 varying from 0.69 to 0.97 with only one coefficient below 0.89. The ICCs of subscores varied from 0.36 to 0.95, finding‘Alignment’and‘Weight shift’in GMPM and‘Protective extension’in QUEST highly reliable. The subscores‘Dissociated movements’in GMPM and QUEST, and‘Grasp’in QUEST were the least reliable, and recommendations are made to increase reliability of these subscores. Video scoring was time consuming, but was found to offer many advantages; the possibility to review performance, to use special trained observers for scoring and less demanding assessment for the children.
Lipopolysaccharide O-Antigen Antibody-Based Detection of the Fish Pathogen Flavobacterium psychrophilum

Several yellow-pigmented species within the family Flavobacteriaceae are commonly associated with diseases in fish and are difficult to speciate due to their fastidious, slow-growing nature and cross-reactive antigens. Here we report the development of specific, antibody-diagnostic tests for Flavobacterium psychrophilum, the aetiological agent of rainbow trout fry syndrome and bacterial cold water disease. A unique antigen from F. psychrophilum, the lipopolysaccharide (LPS) O-polysaccharide (O-PS), formed the basis for the antibody test. LPS O-PS was purified and conjugated to keyhole limpet haemocyanin and bovine serum albumin for the generation of rabbit immune sera and the development of antibody-based diagnostic tests. Rabbit polyclonal anti-O-PS serum was highly specific for F. psychrophilum, without the need for prior cross-absorption with related bacteria and was the basis of an effective ELISA diagnostic test. Antibodies were purified from rabbit anti-O-PS serum and adsorbed onto coloured latex beads for the development of a specific, bead agglutination assay for F. psychrophilum.
Occupational Stress, Symptoms of Burnout in the Workplace and Work Satisfaction of the Age-diverse Employees

Abstract Background and Purpose: Age diverse employees are faced with different types of occupational stress and different symptoms of burnout when carrying out their work. Therefore, the role of age in job design and implementation of work should not be ignored. The main aim of this paper is to investigate the age differences of occupational stress and symptoms of burnout of employees and to analyze the impact of occupational stress, symptoms of burnout and age on employees’ work satisfaction. Methodology: The paper is based on research that includes a survey of employees in two age groups: younger employees under 50 years of age and older employees between 50 to 65 years of age. Factor analysis was used to form the constructs of occupational stress, symptoms of burnout and employees’ work satisfaction. The non-parametric Mann-Whitney U test was used to test differences in the obtained constructs of occupational stress and symptoms of burnout in the workplace between two independent groups. The multiple regression analysis was used to examine the impact of occupational stress, symptoms of burnout and age on employees’ work satisfaction. Results: The results show there are statistically significant differences in occupational stress and symptoms of burnout in the workplace between older and younger employees. On average, younger employees perceived higher levels of occupational stress and burnout as compared to the older group. Research results also show that occupational stress, behavioral symptoms and emotional symptoms of burnout, as well as age, have a significant impact on employees’ work satisfaction. Conclusion: Managing diversity requires a strategic approach to managing people at work. Therefore, this research adds to the body of knowledge by pointing out the relationship between age and occupational stress and burnout symptoms. Because the role of age in job design has largely been ignored, these relationships have not been studied enough.
Multichannel Fluorescence Spinning Disk Microscopy Reveals Early Endogenous CD4 T Cell Recruitment in Contact Sensitivity via Complement1

Contact sensitivity (CS) is one of the primary in vivo models of T cell-mediated inflammation. The presence of CS-initiating CD4 T lymphocytes at the time of challenge is essential for transfer and full development of the late phase CS inflammatory response. From this observation investigators have speculated that early recruitment of CD4 T cells to the site of challenge must occur. Moreover, there must be rapid synthesis/release and disappearance of an important mediator during the first hours after hapten challenge. Using spinning disk confocal microscopy, we observed the very early effector events of the immune response. Simultaneous, real-time visualization of predominant neutrophil and extremely rare CD4 T cell trafficking in the challenged skin vasculature was noted (one rolling CD4 T cell for every 10–18 rolling and adherent neutrophils). We demonstrate that neutrophil adhesion during the early CS response was reduced in C5a receptor-deficient (C5aR−/−) mice or leukotriene B4 receptor antagonist-treated mice, whereas CD4 T cell recruitment was only inhibited in C5aR−/− mice. In line with these observations, leukocyte infiltration and the associated tissue damage were significantly reduced in C5aR−/− mice but not in leukotriene B4 receptor antagonist-treated wild-type mice 24 h after challenge. C5a receptor expression on T cells and not on tissue resident cells was important for the development of a CS response. Thus, by using spinning disk confocal microscopy we visualized the early events of an adaptive immune response and identified the rare but essential recruitment of CD4 T cells via the complement pathway.
Standing orders for influenza vaccination increased vaccination rates in inpatient settings compared with community rates.

BACKGROUND Hospitalization of older adults during the period of influenza vaccination in the fall of each year presents a barrier to immunization against influenza. This study evaluates a program using standing orders for influenza vaccination to increase vaccination rates among hospitalized older adults and to determine the effect of vaccination on readmission rates for influenza-like illness. METHODS An influenza vaccination program using a standing order policy was implemented to vaccinate all consenting persons 65 years and older prior to hospital discharge. This was a prospective, single center, cohort study in a tertiary care university teaching hospital during an 8-week vaccination period in the fall of 1994 and follow-up during the subsequent influenza season. The vaccination status of each patient was recorded as no vaccination, vaccination received in hospital, or vaccination in the community prior to or after the hospitalization. Hospital vaccination rates were compared with the rate of vaccination of older adults in the community. During the subsequent influenza season, the number of subjects reporting symptoms of influenza-like illness (ILI) or who were readmitted to hospital with influenza-related illness was compared in an analysis of vaccinated versus unvaccinated subjects. RESULTS Seven hundred and sixty-one patients were interviewed, and 332 of these individuals had been vaccinated in the community prior to their hospital admission. Of the remaining 429 unvaccinated patients who were eligible for vaccination in the study, 171 were vaccinated in our immunization program, eight were vaccinated in the community after discharge, and 244 were not vaccinated. We were able to increase the absolute vaccination rate by 22%, when compared with community rates, with our immunization program. The number of subjects with ILI symptoms or readmission to hospital was too small to compare the vaccinated to the unvaccinated group in the study. CONCLUSIONS An inpatient influenza immunization program using a standing order policy was able to target a particularly high-risk subset of persons 65 years and over who might otherwise have not received influenza vaccination.
Morphological and Microstructural Alterations of the Articular Cartilage and Bones during Treadmill Exercises with Different Additional Weight-Bearing Levels

The aim of this study was to investigate the morphological and microstructural alterations of the articular cartilage and bones during treadmill exercises with different exercise intensities. Sixty 5-week-old female rats were randomly divided into 10 groups: five additional weight-bearing groups (WBx) and five additional weight-bearing with treadmill exercise groups (EBx), which were subjected to additional weight bearing of x% (x = 0, 5, 12, 19, and 26) of the corresponding body weight of each rat for 15 min/day. After 8 weeks of experiment, the rats were humanely sacrificed and their bilateral intact knee joints were harvested. Morphological analysis of the cartilages and microcomputed tomography evaluation of bones were subsequently performed. Results showed that increased additional weight bearing may lead to cartilage damage. No significant difference was observed among the subchondral cortical thicknesses of the groups. The microstructure of subchondral trabecular bone of 12% and 19% additional weight-bearing groups was significantly improved; however, the WB26 and EB26 groups showed low bone mineral density and bone volume fraction as well as high structure model index. In conclusion, effects of treadmill exercise on joints may be associated with different additional weight-bearing levels, and exercise intensities during joint growth and maturation should be selected reasonably.
Antecedents of intensified job demands: evidence from Austria

Purpose In order to understand the driving forces behind intensified job demands (IJDs), the purpose of this paper is to examine demographic factors, structural work-related factors, personal and job resources as antecedents of IJDs. Design/methodology/approach The study is based on cross-sectional (n=4,963) and longitudinal (n=2,055) quantitative data sets of Austrian employees. Data sets were analyzed via regression analyses. Findings The results showed that IJDs, as assessed through five sub-dimensions: work intensification, intensified job-related, career-related planning and decision-making demands, intensified demands for skills and for knowledge-related learning, remained fairly stable overtime. The most consistent antecedents of IJDs were personal initiative and ICT use at work. Job resources, e.g. variety of tasks and lacking support from supervisor, related to four sub-dimensions of IJDs. Research limitations/implications The findings suggest that personal (being initiative) and job resources (task variety) may have negative effects as they associated with IJDs. Moreover, supervisors’ support is crucial to counteract IJDs. Practical implications Employers should recognize that certain personal (e.g. personal initiative) and job-related resources (e.g. lacking supervisory support) might implicate higher IJDs, which, in turn, may cause more job strain as IJDs can be conceived as job stressors. Originality/value IJDs have received very little research attention because they are new job demands, which however, can be expected to increase in future due to faster technological acceleration in working life. The study has methodological value as longitudinal design was applied.
Cardiac and renal prostaglandin I2. Biosynthesis and biological effects in isolated perfused rabbit tissues.

Both the isolated perfused rabbit heart and kidney are capable of synthesizing prostaglandin (PG) I(2). The evidence that supports this finding includes: (a) radiochemical identification of the stable end-product of PGI(2), 6-keto-PGF(1alpha), in the venous effluent after arachidonic acid administration; (b) biological identification of the labile product in the venous effluents which causes relaxation of the bovine coronary artery assay tissue and inhibition of platelet aggregation; and (c) confirmation that arachidonic acid and its endoperoxide PGH(2), but not dihomo-gamma-linolenic acid and its endoperoxide PGH(1), serve as the precursor for the coronary vasodilator and the inhibitor of platelet aggregation. The rabbit heart and kidney are both capable of converting exogenous arachidonate into PGI(2) but the normal perfused rabbit kidney apparently primarily converts endogenous arachidonate (e.g., generated by stimulation with bradykinin, angiotensin, ATP, or ischemia) into PGE(2); while the heart converts endogenous arachidonate primarily into PGI(2). Indomethacin inhibition of the cyclo-oxygenase unmasks the continuous basal synthesis of PGI(2) by the heart, and of PGE(2) by the kidney. Cardiac PGI(2) administration causes a sharp transient reduction in coronary perfusion pressure, whereas the intracardiac injection of the PGH(2) causes an increase in coronary resistance without apparent cardiac conversion to PGI(2). The perfused heart rapidly degrades most of the exogenous endoperoxide probably into PGE(2), while exogenous PGI(2) traverses the heart without being metabolized. The coronary vasoconstriction produced by PGH(2) in the normal perfused rabbit heart suggests that the endoperoxide did not reach the PGI(2) synthetase, whereas the more lipid soluble precursor arachidonic acid (exogenous or endogenous) penetrated to the cyclooxygenase, which apparently is tightly coupled to the PGI(2) synthetase.
Structural Basis for p53 Binding-induced DNA Bending*

Specific p53 binding-induced DNA bending has important biological implications such as transcription activation. However, the detailed structures of the bent DNA and the p53-DNA complex are still unavailable, hampering our understanding of the mechanism for p53-induced DNA bending and its consequent biological significance. To gain insight into the p53 binding-induced DNA bending, we performed molecular dynamics simulations on DNA segments with the consensus sequence for p53-specific binding, half site DNA-p53 complexes, and full site DNA-p53 complexes. We show that each DNA-bound p53 core domain caused a local DNA conformational change within the quarter site; upon the binding of the p53 dimer, there was an apparent DNA bending at the center of the half site; when bound with two p53 dimers, the full site DNAs with two different sequences bent 20 and 35°, respectively. These results are in agreement with experimental observations. Our simulations demonstrate that the two p53 dimers favored a staggered conformation in which they make favorable interactions at the interface. This dimer-dimer interface organization necessitated conformational changes in the DNA, leading to the bending at the center of the full site, which in turn is dependent on the DNA sequence. Overall, our results provide the detailed atomic model for the DNA-p53 tetramer complex and delineate the roles of DNA-p53, p53 dimer-dimer interactions, and DNA sequence in specific p53 binding-induced DNA conformational changes.
How Effective Was the UK Carbon Tax?—A Machine Learning Approach to Policy Evaluation

Carbon taxes are commonly seen as a rational policy response to climate change, but little is known about their performance from an ex-post perspective. This paper analyzes the emissions and cost impacts of the UK CPS, a carbon tax levied on all fossil-fired power plants. To overcome the problem of a missing control group, we propose a novel approach for policy evaluation which leverages economic theory and machine learning techniques for counterfactual prediction. Our results indicate that in the period 2013-2016 the CPS lowered emissions by 6.2 percent at an average cost of € 18 per ton. We find substantial temporal heterogeneity in tax-induced impacts which stems from variation in relative fuel prices. An important implication for climate policy is that a higher carbon tax does not necessarily lead to higher emissions reductions or higher costs.
The relationship between poverty and inequality: Resource constraint mechanisms

This paper reviews the evidence of how the welfare state can shape the relationship between economic inequality and poverty through the channels of taxes, transfers and public good provision. In particular, we examine how the quantity, and to some extent the quality, of resources that can be raised to tackle poverty may be influenced or constrained by high levels of inequality.