Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Nisoldipine on Endothelin‐1— and Angiotensin II‐Induced Immediate/Early Gene Expression and Protein Synthesis in Adult Rat Ventricular Cardiomyocytes

The cellular mechanisms by which dihydropyridine-type calcium antagonists lead to regression of hypertension-related cardiac hypertrophy have not been clarified. We previously showed that angiotensin II (AII) and endothelin-1 (ET-1) induce protein synthesis in isolated adult rat cardiomyocytes, probably through protein kinase C (PKC) as second messenger and the gene product of the early growth response gene-1 (Egr-1) as third messenger. We now show that the dihydropyridine derivative nisoldipine inhibits AII- and ET-1-induced protein synthesis at low concentrations (IC50 7.5 nM for 0.1 microM ET). Induction of c-fos and Egr-1 mRNA by AII and ET was completely blocked by nisoldipine. Therefore, nisoldipine may influence the signal transduction pathway, i.e., through PKC. These results provide a potential pressure-independent mechanism by which nisoldipine may influence development of cardiac hypertrophy.
Multiple Access Channel : Combining Information and Queueing Theory

Multiple access of a single receiver by many transmitters is studied extensively by information theorists and queueing theorists. Information theorists assume that each transmitter has an infinite pool of data be transmitted. They ignore the random nature of messages arrivals. This trivialization enables them to study more accurate models of noise and interference at the receiver. On the other hand, queueing theorists ignore (or trivialize) the noise and interference phenomenon at the receiver. This enables them to isolate the effects of the random arrival of messages. Although multiple access is one of the best understood channels by information theorists, they can not address the issues of delay with their assumptions (since all data is assumed to be already present in the transmitter’s data pool). On the other hand, queueing theory might be assuming some things about physical layer, which are either suboptimal or impossible from an information theoretic point of view. This motivates the need of a combined analysis for more fundamental results [3]. In this article, we discuss [1] and [2], which are one of the few prominent results in this largely baron field [4].
Decision-making for major renewable energy infrastructure

Presents a study into how decision-making for major renewable energy infrastructure projects under the Planning Act 2008 allows for the views of interested parties, such as local people, to be introduced into the proceedings. Reviews key aspects of decision-making under the Act, the methodology of the study, its main findings, and its recommendations for improving public participation, including the provision of enhanced funding.
Binding Site of Macrolide Antibiotics on the Ribosome: New Resistance Mutation Identifies a Specific Interaction of Ketolides with rRNA

ABSTRACT Macrolides represent a clinically important class of antibiotics that block protein synthesis by interacting with the large ribosomal subunit. The macrolide binding site is composed primarily of rRNA. However, the mode of interaction of macrolides with rRNA and the exact location of the drug binding site have yet to be described. A new class of macrolide antibiotics, known as ketolides, show improved activity against organisms that have developed resistance to previously used macrolides. The biochemical reasons for increased potency of ketolides remain unknown. Here we describe the first mutation that confers resistance to ketolide antibiotics while leaving cells sensitive to other types of macrolides. A transition of U to C at position 2609 of 23S rRNA rendered E. coli cells resistant to two different types of ketolides, telithromycin and ABT-773, but increased slightly the sensitivity to erythromycin, azithromycin, and a cladinose-containing derivative of telithromycin. Ribosomes isolated from the mutant cells had reduced affinity for ketolides, while their affinity for erythromycin was not diminished. Possible direct interaction of ketolides with position 2609 in 23S rRNA was further confirmed by RNA footprinting. The newly isolated ketolide-resistance mutation, as well as 23S rRNA positions shown previously to be involved in interaction with macrolide antibiotics, have been modeled in the crystallographic structure of the large ribosomal subunit. The location of the macrolide binding site in the nascent peptide exit tunnel at some distance from the peptidyl transferase center agrees with the proposed model of macrolide inhibitory action and explains the dominant nature of macrolide resistance mutations. Spatial separation of the rRNA residues involved in universal contacts with macrolides from those believed to participate in structure-specific interactions with ketolides provides the structural basis for the improved activity of the broader spectrum group of macrolide antibiotics.
Psychological factors in functional gastrointestinal disorders: characteristics of the disorder or of the illness behavior?

OBJECTIVE This study examines factors affecting the frequency of physician consultations by individuals with functional gastrointestinal disorders (FGD) in a group of subjects with functional dyspepsia or irritable bowel syndrome. Systematic selection of persons who were already seeing a physician for one of these problems was avoided by conducting an epidemiological field study rather than a clinical study. METHODS A representative sample of the German population (N=2201) completed a questionnaire that included, in addition to the criterion (number of physician visits in the past 12 months), items aimed at identifying the target group and questions about physical symptoms, illness behavior, living situation, personality features, and sociodemographic status (a total of 31 predictors). RESULTS Individuals with functional gastrointestinal disorders who consulted a physician for their gastrointestinal disorders and those who did not differed significantly, especially on psychological measures. The differences between these individuals and the general population were greater for the consulters than for the nonconsulters. Multiple regression analyses yielded nine predictors that explained 40.2% of the variance of the criterion. The best predictors of frequency of physician consultations were the duration of periods with symptoms and psychological factors, such as the severity of depression and the patients' views on the cause of their illness. CONCLUSIONS The psychopathology seen in people with functional gastrointestinal disorders is of two types: one is a characteristic of the illness itself and the other leads the individual to consult a physician. When gastroenterologists see patients with such disorders, they can assume that they may be dealing with a self-selected group of individuals with psychological stress. Psychological assessment would, therefore, be useful to determine whether a given individual with FGD might benefit from psychotherapy.
Heavy-tailed queues in the Halfin-Whitt regime

We consider the FCFS G/G/n queue in the Halfin-Whitt regime, in the presence of heavy-tailed distributions (i.e. infinite variance). We prove that under minimal assumptions, i.e. only that processing times have finite 1 + epsilon moment and inter-arrival times have finite second moment, the sequence of stationary queue length distributions, normalized by $n^{\frac{1}{2}}$, is tight. All previous tightness results for the stationary queue length required that processing times have finite 2 + epsilon moment. Furthermore, we develop simple and explicit bounds on the stationary queue length in that setting. When processing times have an asymptotically Pareto tail with index alpha in (1,2), we bound the large deviations behavior of the limiting process, and derive a matching lower bound when inter-arrival times are Markovian. Interestingly, we find that the large deviations behavior of the limit has a sub-exponential decay, differing fundamentally from the exponentially decaying tails known to hold in the light-tailed setting, and answering an open question of Gamarnik and Goldberg. For the setting where instead the inter-arrival times have an asymptotically Pareto tail with index alpha in (1,2), we extend recent results of Hurvich and Reed (who analyzed the case of deterministic processing times) by proving that for general processing time distributions, the sequence of stationary queue length distributions, normalized by $n^{\frac{1}{\alpha}}$, is tight (here we use the scaling of Hurvich and Reed, i.e. Halfin-Whitt-Reed regime). We are again able to bound the large-deviations behavior of the limit, and find that our derived bounds do not depend on the particular processing time distribution, and are in fact tight even for the case of deterministic processing times.
The Power of Ability-Motivation-Opportunity Enhancing Human Resource Management Practices on Organizational Ethical Climate

This paper examined ability-, motivationand opportunity-enhancing human resource management (HRM) practices to achieve organizational ethical climate. Sample sizes of 74 construction companies in Malaysia were selected based on systematic sampling technique. Partial Least Square Structural Equation Modelling (PLS-SEM) of SmartPLS 3.2. 6 software was used to analyse the data. The findings revealed that ability-enhancing HRM practices was related to organizational ethical climate, while motivationand opportunity-enhancing HRM practices did not influence organizational ethical climate. This denoted that ability-enhancing HRM practices played an important role in promoting organizational ethical climate of construction companies in Malaysia. In addition, discussion, implications, directions for future research, and conclusion of the study were also highlighted.
Predicting depression in rheumatoid arthritis: the signal importance of pain extent and fatigue, and comorbidity.

OBJECTIVE To determine the incidence of self-reported depression (SRD) in rheumatoid arthritis and to identify and rank clinically useful predictors of depression. METHODS We assessed 22,131 patients for SRD between 1999 and 2008. We collected demographic, clinical and treatment data, household income, employment and work disability status, comorbidity, scales for function, pain, global, and fatigue, the Regional Pain Scale (RPS), the Symptom Intensity (SI) scale (a linear combination of the RPS and the fatigue scales) and linear combinations of the Health Assessment Questionnaire, pain and global severity. We used logistic regression analyses with multivariable fractional polynomial predictors, and Random Forest analysis to determine the importance of the predictors. RESULTS The cross-sectional prevalence of self-reported depression was 15.2% (95% confidence interval [95% CI] 14.7-15.7%) and the incidence rate was 5.5 (95% CI 5.3-5.7) per 100 patient years of observation. The cumulative risk of SRD after 9 years was 38.3% (95% CI 36.6-40.1%). Almost all variables were significant predictors in logistic models. In Random Forest analyses, the SI scale, followed by comorbidity, best predicted self-reported depression, and no other variable or combination of variables improved prediction compared with the SI scale. CONCLUSION Pain extent and fatigue (SI scale) are the dominant predictors of SRD. These variables, also of central importance in the symptomatology of fibromyalgia, are powerful markers of distress. A strong case can be made for the inclusion of these assessments in routine rheumatology practice. In addition, actual knowledge of comorbidity provides important insights into the patient's global health and associated perceptions.
Perivascular Adipose Tissue Potentiates Contraction of Coronary Vascular Smooth Muscle: Influence of Obesity

Background— This investigation examined the mechanisms by which coronary perivascular adipose tissue (PVAT)–derived factors influence vasomotor tone and the PVAT proteome in lean versus obese swine. Methods and Results— Coronary arteries from Ossabaw swine were isolated for isometric tension studies. We found that coronary (P=0.03) and mesenteric (P=0.04) but not subcutaneous adipose tissue augmented coronary contractions to KCl (20 mmol/L). Inhibition of CaV1.2 channels with nifedipine (0.1 µmol/L) or diltiazem (10 µmol/L) abolished this effect. Coronary PVAT increased baseline tension and potentiated constriction of isolated arteries to prostaglandin F2&agr; in proportion to the amount of PVAT present (0.1–1.0 g). These effects were elevated in tissues obtained from obese swine and were observed in intact and endothelium denuded arteries. Coronary PVAT also diminished H2O2-mediated vasodilation in lean and, to a lesser extent, in obese arteries. These effects were associated with alterations in the obese coronary PVAT proteome (detected 186 alterations) and elevated voltage-dependent increases in intracellular [Ca2+] in obese smooth muscle cells. Further studies revealed that the Rho-kinase inhibitor fasudil (1 µmol/L) significantly blunted artery contractions to KCl and PVAT in lean but not obese swine. Calpastatin (10 &mgr;mol/L) also augmented contractions to levels similar to that observed in the presence of PVAT. Conclusions— Vascular effects of PVAT vary according to anatomic location and are influenced by an obese phenotype. Augmented contractile effects of obese coronary PVAT are related to alterations in the PVAT proteome (eg, calpastatin), Rho-dependent signaling, and the functional contribution of K+ and CaV1.2 channels to smooth muscle tone.
Effects of different daily protein intake on reproduction in boiler breeder females

Broiler breeder production is an important link in the poultry meat chain. The main goal in broiler breeder production is to provide fertilized settable eggs, for the production of healthy and robust dayold chickens (Zuidhof et al., 2007). Almost 6 million broiler breeders at 200 breeder farms in the Netherlands jointly produce almost 1 billion hatching eggs a year. During the last decade, a major problem in broiler breeder production is a decreasing trend in fertility and hatchability of eggs, especially during the second part of the laying period. Besides many factors, nutrition can play a major role. A negative effect of a high dietary CP during the laying period on fertility and hatchability of eggs has been reported by Pearson and Herron (1982), Whitehead et al. (1985), and Lopez and Leeson (1995). Moreover, Pearson and Herron (1982) reported that a high protein compared to a low protein intake during the laying period, resulted in an increased mortality and malformation of embryos. However, little is known about the effects of different dietary energy levels on reproduction of a modern breeder strain. The aim of the study was to determine the effects of different dietary energy levels on the reproduction of Ross 308 breeders.
A new 3 D Markovian fuzzy approach for increasing the accuracy of measurement of the calcium deposit in 3 D CTA images of the coronary artery

Accurate quantification of calcium deposit is an important task in assessing coronary artery disease, especially when the investigation of the disease progress is considered. The reproducibility and robustness of the segmentation algorithm against partial volume effect and noise is critical for an accurate quantification. While there are several approaches for segmentation of the volume of the blood vessel and hard plaque in the literature, the main drawback of these approaches is in making a deterministic decision in terms of assigning a particular voxel to only one type of tissue (such as blood vessel, hard plaque or surrounding area). However in reality, because of the partial volume effect, a voxel may contain more than one tissue type. In particular, using deterministic methods for quantification of the small objects such as thin blood vessels or hard plaque may lead to inaccurate results and higher inter and intra-scan variability. In this paper, we tackle the problem of the partial volume effect using a 3D adaptive fuzzy algorithm incorporating a Markov random field model. The method is shown to more accurately segment the blood vessel, hard plaque and surrounding tissue areas. The algorithm is applied to several datasets and the outcomes have been judged visually by a qualified radiologist. The proposed algorithm has the potential to be applied for the accurate quantification of the degree of stenosis.
Growth Hormone Treatment Does Not Affect Incidences of Middle Ear Disease or Hearing Loss in Infants and Toddlers with Turner Syndrome

Context: No randomized, controlled, prospective study has evaluated the effect of growth hormone (GH) on the rates of middle ear (ME) disease and hearing loss in girls with Turner syndrome (TS). Design: A 2-year, prospective, randomized, controlled, open-label, multicenter, clinical trial (‘Toddler Turner Study’; August 1999 to August 2003) was carried out. Setting: The study was conducted at 11 US pediatric endocrine centers. Subjects: Eighty-eight girls with TS, aged 9 months to 4 years, were enrolled. Intervention: The interventions comprised recombinant GH (50 µg/kg/day, n = 45) or no treatment (n = 43) for 2 years. Main Outcome Measures: The outcome measures included occurrence rates of ear-related problems, otitis media (OM) and associated antibiotic treatments, tympanometric assessment of ME function and hearing assessment by audiology. Results: At baseline, 57% of the girls (mean age = 1.98 ± 1.00 years) had a history of recurrent OM, 33% had undergone tympanostomy tube (t-tube) insertion and 27% had abnormal hearing. There was no significant difference between the treatment groups for annual incidence of OM episodes (untreated control: 1.9 ± 1.4; GH-treated: 1.5 ± 1.6, p = 0.17). A quarter of the subjects underwent ear surgeries (mainly t-tube insertions) during the study. Recurrent or persistent abnormality of ME function on tympanometry was present in 28–45% of the girls without t-tubes at the 6 postbaseline visits. Hearing deficits were found in 19–32% of the girls at the annual postbaseline visits. Most of these were conductive deficits, however, 2 girls had findings consistent with sensorineural hearing loss, which was evident before 3 years of age. Conclusions: Ear and hearing problems are common in infants and toddlers with TS and are not significantly influenced by GH treatment. Girls with TS need early, regular and thorough ME monitoring by their primary care provider and/or otolaryngologist, and at least annual hearing evaluations by a pediatric audiologist.
The separation of property and control and its costs a century old problem that seems modern

The Agency Costs resulting from the conflict between principals and agents, due to the separation of ownership and control in the capitalist enterprise, was analyzed in many works of the last century. Could we assume that the current globalization of companies has increased the differences between principals and agents? Does this scenario lead to an increase in Agency Costs in those companies with the greatest presence in the global economy? The objective of this article is to compile studies that will allow us to answer these questions affirmatively and conclude that large transnational, multinational or global companies involve higher Agency Costs than those that remain within national borders.
Massive transfusion in children and neonates

Resuscitation of children and neonates with severe or refractory bleeding due to surgery or trauma often requires massive transfusion (MT). Findings from recent studies have led to a better understanding of the complex pathophysiology in massive haemorrhage and the effects of MT on haemostasis. Current management of the massively bleeding adult patient has evolved over the past few decades, shifting to early transfusion of products in a balanced ratio as part of MT protocols (MTPs). Paediatric data on successful management of MT are limited and the optimal transfusion approach is currently unknown, leading to practice variability among institutions, depending on resource availability and patients' needs. Here, we review new important concepts in the biology of massive bleeding and MT, outline important management principles and current practices, and highlight available relevant adult and paediatric data.
Vascularized fibular graft for management of severe osteomyelitis of the upper extremity

The authors analyzed 14 patients with severe osteomyelitis of the upper extremity between 1985 and 1992, managed with the vascularized fibular graft. Eleven radii, two humeri and one ulna were reconstructed. Bone loss after resection ranged from 6 to 12 cm (mean 8.14 cm). Follow‐up ranged from 8 months to 7 years and 10 months (mean 3 years and 3 months). The therapeutic applications of the vascularized fibular graft in severe bone infections of the upper extremity were discussed and the good results of this surgical procedure established it as a good option for treatment. Morbidity at the donor site was minimal. © 1994 Wiley‐Liss, Inc.
Does Disability Insurance Improve Health and Well-Being?

The purpose of disability insurance (DI) is to protect people with health problems that limit their ability to work. We evaluate the effectiveness of DI benefit programs in delivering this protection by following peopleâ€™s health and financial well-being after the take-up of DI benefits. This paper takes advantage of internationally harmonized panel data and the differences across DI programs in Europe and the United States, as well as their changes over time. We use several econometric approaches to account for the potential endogeneity of DI enrollment and sample selectivity. We find that self-reported health stabilizes after DI benefit receipt. Mental health improves more for DI benefit recipients than non-recipients relative to the beginning of DI benefit receipt. This effect is stronger in countries with more generous DI systems. The effects on objective health measures are positive but largely insignificant.
Effects of carcinogenic agents upon different mechanisms for intragenic recombination in mammalian cells.

A growing body of carcinogens are known to affect genetic recombination in mammalian cells and to thereby interfere with the process of carcinogenesis. In order to screen for recombinogenic effects of chemical and physical agents a variety of in vitro assay systems utilizing mammalian cells have been developed. However, the effects of potential carcinogens differ in these different systems. In order to investigate this phenomenon further, we have employed two different assay procedures, involving spontaneous duplication mutants in mammalian cells, which respond to homologous or non-homologous recombination. Four carcinogens were investigated, i.e. Aroclor 1221, benzene, methylmethanesulphonate (MMS) and thiourea, as were gamma- and UV-irradiation. With the exception of thiourea all of these factors resulted in elevated frequencies of homologous recombination. On the other hand, only UV-irradiation affected the rate of non-homologous recombination. These results indicate that substrate length and/or the recombination mechanism may influence the recombinogenic response of mammalian fibroblasts to carcinogenic factors. Thus, procedures for recombinogenic effects of carcinogens should consider the different pathways of recombination occurring in mammalian cells.