Miracle-dz/UniFAR-FTUs huggingface dataset:
Alpha4 integrins as therapeutic targets in autoimmune disease.

In this issue of the Journal, two groups of investigators report on clinical trials of natalizumab, a recombinant monoclonal antibody against α4 integrins, for the treatment of multiple sclerosis1 and Crohn's disease.2 Miller et al. report that a group of patients with multiple sclerosis who received monthly injections of natalizumab had significantly fewer new inflammatory central nervous system lesions than the placebo group (a reduction of approximately 90 percent) and had approximately half as many clinical relapses.1 Ghosh et al. report that patients with Crohn's disease also had an improved response to natalizumab,2 with response and remission rates that .
Biofeedback-based interventions in somatoform disorders: a randomized controlled trial

Background and aim: The aim of the controlled therapy study was to evaluate the effect of a 6 session biofeedback intervention program on cognitive aspects of patients with somatoform disorders. The treatment consisted of psycho-physiological demonstrations how mental processes can influence biological functions. We expected this treatment to be of high credibility, to change maladaptive cognitions, to enhance acceptance of psychosocial causal attribution and to improve coping. Methods: Patients were assessed using a structured interview to diagnose somatization syndrome (SSI-8) and comorbidity according to DSM-IV criteria. Fifty patients were recruited and randomly assigned to biofeedback treatment or control relaxation group. Participants completed a questionnaire battery assessing cognitive characteristics, causal attributions and controllability before and after intervention as well as evaluation protocols for each session. Results: The results suggest that biofeedback modified the patients' cognitive schemata: Patients with somatization syndrome of the biofeedback group showed a greater reduction of catastrophizing of somatic sensations and higher acceptance of psychosocial causal attributions than the control group. Both groups improved significantly in the conviction of self-efficacy.
Physical activity and metabolic syndrome in liver transplant recipients

There is a high prevalence of metabolic syndrome in liver transplant recipients, a population that tends to be physically inactive. The aim of this study was to characterize physical activity and evaluate the relationship between physical activity and metabolic syndrome after liver transplantation. A cross‐sectional analysis was performed in patients more than 3 months after transplantation. Metabolic syndrome was classified according to National Cholesterol Education Panel Adult Treatment Panel III guidelines. Physical activity, including duration, frequency, and metabolic equivalents of task (METs), was assessed. The study population consisted of 204 subjects, with 156 more than 1 year after transplantation. The median time after transplantation was 53.5 months (range = 3‐299 months). The mean duration of exercise was 90 ± 142 minutes, and the mean MET score was 3.6 ± 1.5. Metabolic syndrome was observed in 58.8% of all subjects and in 63.5% of the subjects more than 1 year after transplantation. In a multivariate analysis involving all subjects, metabolic syndrome was associated with a time after transplantation greater than 1 year [odds ratio (OR) = 2.909, 95% confidence interval (CI) = 1.389‐6.092] and older age (OR = 1.036, 95% CI = 1.001‐1.072). A second analysis was performed for only patients more than 1 year after transplantation. In a multivariate analysis, metabolic syndrome was associated with lower exercise intensity (OR = 0.690, 95% CI = 0.536‐0.887), older age (OR = 1.056, 95% CI = 1.014‐1.101), and pretransplant diabetes (OR = 4.246, 95% CI = 1.300‐13.864). In conclusion, metabolic syndrome is common after liver transplantation, and the rate is significantly higher in patients more than 1 year after transplantation. The observation that exercise intensity is inversely related to metabolic syndrome after transplantation is novel and suggests that physical activity might provide a means for reducing metabolic syndrome complications in liver transplant recipients. Liver Transpl 19:1125–1131, 2013. © 2013 AASLD.
Economics of Software Development

In this paper, we investigate economics of software development. We first identify several dimensions of software quality from user’s perspectives. We model the tradeoff between having more features and functionalities and the ease of learning in usability, and the tradeoffs among ease of use, ease of learning, and usage frequency. Based on the impacts of quality dimensions on user’s utility, we analyze the software monopoly’s economic incentives to provide high quality software products and build analytical model to analyze the software company’s optimal design decisions. (Keywords: Software, Usability, Economics)
Endothelial AT1 and AT2 pathways in aortic responses to angiotensin II after stress and ethanol consumption in rats

Abstract Stress and ethanol are important cardiovascular risk factors. Their vascular and blood pressure (BP) effects were evaluated alone and in combination. Adult male Wistar rats (8–10 per group) were separated into control, ethanol (ethanol 20% in drinking water for 6 weeks), stress (restraint 1 h/d 5 d/week for 6 weeks), and ethanol/stress (in combination) groups. Systolic BP was evaluated weekly. Concentration–response curves for contractile responses to angiotensin II in the absence and the presence of losartan (AT1-blocker), PD123-319 (AT2-blocker), L-NAME (nitric oxide synthase inhibitor), or indomethacin (cyclooxygenase inhibitor) were obtained in isolated intact and endothelium-denuded aortas. Effective concentration 50% (EC50) and maximum response (MR) were compared among groups using MANOVA/Tukey tests. Stress and stress plus ethanol increased BP. Ethanol and stress, alone and in combination, did not alter angiotensin responses of intact aortas. PD123-319 decreased MR to angiotensin II in intact aortas from the ethanol and ethanol/stress groups relative to control in the presence of PD123-319. Losartan increased MR to angiotensin II in intact aortas from the stress and ethanol/stress groups relative to control in the presence of losartan. None of the protocols altered angiotensin responses of denuded aortas. Neither indomethacin nor L-NAME altered angiotensin responses of intact aortas from the experimental groups. Thus ethanol and ethanol plus stress may alter endothelial signaling via AT1-receptors, without changing systemic BP. Stress and stress plus ethanol may alter endothelial signaling via AT2-receptors, and thereby increase BP. Knowledge of such vascular changes induced by stress and/or ethanol may contribute to understanding adverse cardiovascular effects of stress and ethanol consumption in humans.
The mechanism of action of methylprednisolone in the treatment of multiple sclerosis

Methylprednisolone plays an important role in the current treatment of multiple sclerosis (MS), particularly in the acute phase of relapse. It acts in various ways to decrease the inflammatory cycle including: dampening the inflammatory cytokine cascade, inhibiting the activation of T cells, decreasing the extravasation of immune cells into the central nervous system, facilitating the apoptosis of activated immune cells, and indirectly decreasing the cytotoxic effects of nitric oxide and tumor necrosis factor alpha. This paper reviews the most recent observations on these mechanisms both to understand the disease mechanism and its treatment. As more becomes known about these mechanisms, it may become possible to design treatment regimes that are more specific towards both the individual and the disease state.
Histological analysis of experimental wound healing under the action of low power laser [Abstract in English]

Objetivos : verificar histologicamente a cicatrizacao de feridas cutâneas experimentais em Rattus norvergicus quando empregado o laser de baixa potencia. Metodos : foram utilizados 45 animais machos, distribuidos em tres grupos conforme a terapeutica adotada (nao tratados, tratados com laser na dose de 4 J/cm2 e tratados com laser na dose de 8 J/cm2), os quais foram divididos em tres subgrupos conforme o periodo de eutanasia (7, 14 e 21 dias). Foi removido um fragmento cutâneo de 2 cm de diâmetro do dorso de cada animal e a cada 24 horas foi irradiado laser nos fragmentos dos grupos tratados, com a dose estabelecida previamente. Resultados : aos sete dias apos o experimento, os grupos irradiados com laser de baixa potencia apresentaram uma reepitelizacao mais eficiente quando comparados ao grupo nao tratado. Alem disso, os grupos tratados com laser apresentaram uma deposicao de colageno mais acentuada quando transcorridos 14 dias. A dose ajustada em 4 J/cm2 foi mais efetiva. Conclusoes : o laser de baixa potencia otimizou o processo de cicatrizacao de feridas cutâneas experimentais em Rattus norvergicus. A dose ajustada em 4 J/cm2 foi mais efetiva.
Altered responses to hypoglycemia of healthy elderly people.

Many elderly people are treated with medications or are subjected to diseases which can cause hypoglycemia. We conducted the following studies to assess whether alterations in counterregulatory hormone release, decreased awareness of warning symptoms or alterations in psychomotor performance might increase the susceptibility of the elderly to hypoglycemia. Healthy, nonobese young (n = 10, age < 30) and old (n = 9, age > 65) subjects underwent paired hyperinsulinaemic clamp studies (insulin infusion rate 60 mU/m2.min). In the control study, glucose was kept at 5.0 mmol/L for 5 h. In the hypoglycemic study, glucose was kept at 5 mmol/L for 1 h and was lowered in stepwise fashion to 4.4, 3.8, 3.3, and 2.8 mmol/L in each subsequent hour. Subjects were blinded as to which study they were undergoing. Counterregulatory hormones were measured and a hypoglycemic symptom checklist was administered every 15 min in each study. Neuropsychological tests were performed at regular intervals. The glucose threshold for release of counterregulatory hormones was defined as the glucose level at which the values during the hypoglycemic study first exceeded values during the control study by 2 SD. The glucose threshold for glucagon and epinephrine release was higher in the young (approximately 3.3 mmol/L) than the old (approximately 2.8 mmol/L) and the epinephrine responses to hypoglycemia were also greater in the young. The threshold for release of GH (approximately 3.3 mmol/L) and norepinephrine and cortisol (approximately 2.8 mmol/L) was similar in each age group, as was the magnitude of release of these hormones. Although the variance in symptoms scores was large, the elderly appeared to have reduced awareness of the autonomic but not neuroglycopenic symptoms of hypoglycemia. There was no difference between young and old in the effect of hypoglycemia on neuropsychologic tests. We conclude that healthy elderly people may have impaired release of glucagon and epinephrine in response to hypoglycemia and reduced awareness of the autonomic symptoms of hypoglycemia.
LIM protein Ajuba functions as a nuclear receptor corepressor and negatively regulates retinoic acid signaling

Corepressors play an essential role in nuclear receptor-mediated transcriptional repression. In general, corepressors directly bind to nuclear receptors via CoRNR boxes (L/I-X-X-I/V-I) in the absence of ligand and appear to act as scaffolds to further recruit chromatin remodeling complexes to specific target genes. Here, we describe the identification of the multiple LIM domain protein Ajuba as a unique corepressor for a subset of nuclear hormone receptors. Ajuba contains functional nuclear-receptor interacting motifs and selectively interacts with retinoic acid receptors (RARs) and rexinoid receptor (RXRs) subtypes in a ligand-dependent manner. Simultaneous mutation of these motifs abolishes RAR binding and concomitantly leads to loss of repression on RARE reporter genes. P19 cells depleted of Ajuba are highly sensitized to all-trans retinoic acid (atRA)-induced transcription and differentiation. In the absence of atRA, Ajuba can be readily found at the RARE control elements of RAR endogenous target genes. Stimulation of cells with atRA results in the dissociation of Ajuba from these regions. Moreover, we observed that coexpression of the known Ajuba binding partner Prmt5 (protein arginine methyltransferase-5) inhibited the Ajuba/RAR interaction. The high-affinity Ajuba-RAR/RXR interaction site overlaps the region responsible for Ajuba/Prmt5 binding, and thus binding appears to be mutually exclusive, providing a potential mechanism for these observations. Identification of Ajuba as a unique corepressor for nuclear receptors sheds new light on mechanisms for nuclear receptor-mediated repression and provides a unique target for developing more effective therapeutics to modulate this important pathway.
The human L‐myc gene is expressed as two forms of protein in small cell lung carcinoma cell lines: detection by monoclonal antibodies specific to two myc homology box sequences.

The L‐myc gene is the third member of the myc family of proto‐oncogenes. Amplification and elevated expression of the L‐myc gene has been detected in a subset of small cell lung carcinoma (SCLC) cell lines. The biological properties and functions of the L‐myc gene and its product have not yet been elucidated. Monoclonal antibodies against two myc homology boxes were used to characterize the L‐myc gene product. These antibodies react with two groups of polypeptides of apparent masses of 60, 61 and 66 kd (the long forms), and 34 and 37 kd (the short forms) in SCLC cells expressing L‐myc transcripts. The long form L‐myc proteins are associated with the nuclear fraction of the cells. The short form L‐myc proteins are present in the cytoplasmic fraction, though diffusion of the short forms from the nucleus during cell fractionation cannot be ruled out. The half‐life of the long form polypeptides is approximately 45‐90 min. The short form polypeptides have a half‐life of approximately 120‐180 min. The L‐myc protein is not detectable in the mitotic cells, suggesting that the L‐myc protein expression is tightly regulated during the cell cycle.
Transient-State Analysis of Metabolic Fluxes in Crabtree-Positive and Crabtree-Negative Yeasts

In bakers' yeast, an immediate alcoholic fermentation begins when a glucose pulse is added to glucose-limited, aerobically grown cells. The mechanism of this short-term Crabtree effect was investigated via a comparative enzymic analysis of eight yeast species. It was established that the fermentation rate of the organisms upon transition from glucose limitation to glucose excess is positively correlated with the level of pyruvate decarboxylase (EC 4.1.1.1). In the Crabtree-negative yeasts, the pyruvate decarboxylase activity was low and did not increase when excess glucose was added. In contrast, in the Crabtree-positive yeasts, the activity of this enzyme was on the average sixfold higher and increased after exposure to glucose excess. In Crabtree-negative species, relatively high activities of acetaldehyde dehydrogenases (EC 1.2.1.4 and EC 1.2.1.5) and acetyl coenzyme A synthetase (EC 6.2.1.1), in addition to low pyruvate decarboxylase activities, were present. Thus, in these yeasts, acetaldehyde can be effectively oxidized via a bypass that circumvents the reduction of acetaldehyde to ethanol. Growth rates of most Crabtree-positive yeasts did not increase upon transition from glucose limitation to glucose excess. In contrast, the Crabtree-negative yeasts exhibited enhanced rates of biomass production which in most cases could be ascribed to the intracellular accumulation of reserve carbohydrates. Generally, the glucose consumption rate after a glucose pulse was higher in the Crabtree-positive yeasts than in the Crabtree-negative yeasts. However, the respiratory capacities of steady-state cultures of Crabtree-positive yeasts were not significantly different from those of Crabtree-negative yeasts. Thus, a limited respiratory capacity is not the primary cause of the Crabtree effect in yeasts. Instead, the difference between Crabtree-positive and Crabtree-negative yeasts is attributed to differences in the kinetics of glucose uptake, synthesis of reserve carbohydrates, and pyruvate metabolism.
A Cost Effective and Preventive Approach to Avoid Integration Faults Caused by Mistakes in Distribution of Software Components

In distributed software and hardware environments, ensuring proper operation of software is a challenge. The complexity of distributed systems increases the number of integration faults resulting from configuration errors in the distribution of components. Therefore, the main contribution of this work is a change in perspective, where integration faults (in the context of mistakes in distribution of components) are prevented rather than being dealt with through postmortem approaches. To this purpose, this paper proposes a preventive, low cost, minimally intrusive, and reusable approach. The generation of hash tags and a built-in version control for the application are at the core of the solution. Prior to deployment, the tag generator creates a list of components along with their respective tags, which will be a part of the deployment package. During production and execution of the application, on demand, the version control compares the tag list with the components of the user station and shows the discrepancies. The approach was applied to a complex application of a large company and was proven to be successful by avoiding integration faults and reducing the diagnosis time by 65%.
Etude et caractérisation d'interconnexions intermétalliques à partir de plot de cuivre et d'alliage SnAgCu pour l'empilement tridimentionnel de composants actifs

Les objectifs technologiques de l'industrie de la microelectronique sont largement dictes par la loi de Moore qui vise une reduction permanente de la taille des transistors. Depuis peu l'integration tridimensionnel de composant actif se presente comme une voie d'integration alternative a la loi de Moore. Selon cette strategie, les composants sont interconnectes selon l'axe verticale au moyen de plots de cuivre et d'un alliage a base d'etain (SnAgCu). L'assemblage est alors realise par un brasage eutectique de l'alliage SnAgCu qui genere une formation de composes intermetalliques (Cu6Sn6 et Cu3Sn) a l'interface entre les plots de cuivre et l'alliage. Or, ces composes intermetalliques sont parfois decrits dans la litterature comme facteur affaiblissant la fiabilite mecanique de l'interconnexion. Par ailleurs cette reactivite interfaciale s'accompagne de l'apparition microcavites de type trous Kirkendall susceptibles d'etre a l'origine de ruptures d'interconnexions notee lors de tests de vieillissement. Ce memoire est consacre a la caracterisation metallurgique du systeme d'interconnexion par brasage dont les dimensions sont celles des prototypes actuels c'est-a-dire 25µm. L'etude se concentrera successivement sur les aspects relatifs a la microstructure de l'alliage SnAgCu, a la reactivite interfaciale des systemes Cu/SnAgCu et Ni/SnAgCu puis a la fiabilite mecanique du systeme d'interconnexion. Ces thematiques seront investiguees en fonction de la contrainte thermique et au cours des differentes etapes d'integration jusqu'a l'assemblage de composant. Le caractere critique de la problematique reside dans le fait que les dimensions du systeme, deja faibles, ont vocation a se reduire, rendant de plus en plus importante la proportion du volume de l'alliage occupee par ces formations interfaciales.
Protein targeting by the signal recognition particle

Abstract Protein targeting by the signal recognition particle (SRP) is universally conserved and starts with the recognition of a signal sequence in the context of a translating ribosome. SRP54 and FtsY, two multidomain proteins with guanosine triphosphatase (GTPase) activity, are the central elements of the SRP system. They have to coordinate the presence of a signal sequence with the presence of a vacant translocation channel in the membrane. For coordination the two GTPases form a unique, nearly symmetric heterodimeric complex in which the activation of GTP hydrolysis plays a key role for membrane insertion of substrate proteins. Recent results are integrated in an updated perception of the order of events in SRP-mediated protein targeting.
BIOACTIVITY STUDIES ON BARRINGTONIA RACEMOSA (LAM.) BARK

Barringtonia racemosa (Lam.), a mangrove tree belongs to the family, Lecythidaceae, well known in traditional medicine systems in Bangladesh for the treatment of various ailments. In the present study, several pharmacological investigations were carried out to ascertain bioactivity of the ethanol bark extract. Antioxidant activity of the extract was evaluated by free-radical-scavenging assay using 1,1,-diphenyl-2picrylhydrazyl (DPPH). Acetic acid induced writhing method was utilized to evaluate analgesic activity. For the evaluation of anti-diarrhoeal activity, castor oil induced diarrheal model was applied. Antibacterial activity assessment was performed by Disc diffusion assay. The extract showed IC50 value of 31.90 μg/mL in DPPH assay. The extract showed significant (p<0.001) and dose dependent analgesic activity with 36.3 and 63.8% inhibition of writhing at the doses of 250 and 500 mg/kg body-weight, respectively. The extract exhibited significant (p<0.001) reduction in the total number of faeces as well as prolongation of onset of diarrhoea at both doses of 250 and 500 mg/kg body-weight. In antibacterial test, the extract, showed activity against the bacterial strains namely S. aureus, S. epidermidis, E. coli, S. dysenteriae, V. cholera, and proteus sp. at the doses of 250 and 500 μg/disc. The results suggest that the ethanol bark extract of B. racemosa could be used as potential antioxidant, analgesic, anti-diarrheal, and antibacterial agent and demands further investigations to identify underlying mechanisms responsible for bioactivities.
An artificial bee colony based optimal placement and sizing of distributed generation

In this work, it has been demonstrated how artificial bee colony algorithm can be successfully utilized to solve an optimal DG placement problem, considering both technical and economic objectives. The technical objectives try to minimize line loss, the effect of voltage sag problem, and the variation in node voltage deviation in the distribution network. The economical objectives try to minimize operational costs of DG placements. This problem has been formulated as a constrained, multi-objective optimization problem using weighting method and penalty function approach and it has been successfully implemented for a 34-bus radial distribution system. The results are compared with that of the GA method and aptly demonstrate the utility of the proposed algorithm.