Miracle-dz/UniFAR-FTUs huggingface dataset:
Ensemble clustering in deterministic ensemble

Ensemble clustering (EC) can arise in data assimilation with ensemble square root filters (EnSRFs) using non-linear models: an M-member ensemble splits into a single outlier and a cluster of M 1 members. The stochastic Ensemble Kalman Filter does not present this problem. Modifications to the EnSRFs by a periodic resampling of the ensemble through random rotations have been proposed to address it. We introduce a metric to quantify the presence of EC and present evidence to dispel the notion that EC leads to filter failure. Starting from a univariate model, we show that EC is not a permanent but transient phenomenon; it occurs intermittently in non-linear models. We perform a series of data assimilation experiments using a standard EnSRF and a modified EnSRF by a resampling though random rotations. The modified EnSRF thus alleviates issues associated with EC at the cost of traceability of individual ensemble trajectories and cannot use some of algorithms that enhance performance of standard EnSRF. In the non-linear regimes of low-dimensional models, the analysis root mean square error of the standard EnSRF slowly grows with ensemble size if the size is larger than the dimension of the model state. However, we do not observe this problem in a more complex model that uses an ensemble size much smaller than the dimension of the model state, along with inflation and localisation. Overall, we find that transient EC does not handicap the performance of the standard EnSRF.
Region‐selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain

Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl‐tert‐butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hafter endotoxin injection. Animals were killed 7 days post‐injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open‐channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (two‐ to threefold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (> 50%) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl‐tert‐butyl nitrone treatment resulted in a partial inhibition (approx. 25% decrease) of the lipopolysaccharide‐induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide‐induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.
Cost-effectiveness of clozapine compared with conventional antipsychotic medication for patients in state hospitals.

BACKGROUND An open-label, randomized controlled trial compared clozapine with physicians'-choice medications among long-term state hospital inpatients in Connecticut. The goal was to examine clozapine's cost-effectiveness in routine practice for people experiencing lengthy hospitalizations. METHODS Long-stay patients with schizophrenia in a state hospital were randomly assigned to begin open-label clozapine (n = 138) or to continue receiving conventional antipsychotic medications (n = 89). We interviewed study participants every 4 months for 2 years to assess psychiatric symptoms and functional status, and we collected continuous measures of prescribed medications, service utilization, and other costs. We used both parametric and nonparametric techniques to examine changes in cost and parametric analyses to examine changes in effectiveness. We used bootstrap techniques to estimate incremental cost-effectiveness ratios and create cost-effectiveness acceptability curves. RESULTS Both groups incurred similar costs during the 2-year study period, with a trend for clozapine to be less costly than usual care in the second study year. Clozapine was more effective than usual care on many but not all measures. With the use of effectiveness measures that favored clozapine (extrapyramidal side effects, disruptiveness), bootstrap techniques indicated that, even when a payer is unwilling to incur any additional cost for gains in effectiveness, the probability that clozapine is more cost-effective than usual care is at least 0.80. These findings were not as evident when outcomes where clozapine was not clearly superior (psychotic symptoms, weight gain) were examined. CONCLUSION Clozapine demonstrated cost-effectiveness on some but not all measures of effectiveness when the alternative was a range of conventional antipsychotic medications.
Precise Role of Acid in Non-Erosive Reflux Disease

The fundamental abnormality in gastroesophageal reflux disease is exposure of the esophageal epithelium to acidic gastric contents, resulting in histopathologic injury and/or symptoms. With increasing understanding of gastroesophageal reflux disease, non-erosive reflux disease (NERD) is found to account for >50% of cases involving gastroesophageal reflux. There is a good correlation between esophageal acid exposure (EAE) and endoscopic changes. Duration of EAE correlates with severity of erosive esophagitis (EE), and the number of prolonged acid reflux episodes and esophageal exposure to acid and pepsin is increased in more severe reflux. However, there is no convincing evidence to support a significant difference in the acid secretory capacity between patients with NERD or EE. Although acid reflux gives rise to similar symptoms in both NERD and EE patients, the underlying mechanism of acid injury may be different. Dilated intercellular spaces may be responsible for the enhanced perception of proximal acid reflux and dilated intercellular spaces are a feature of NERD patients, irrespective of EAE, and can be considered an objective, structural marker of reflux symptoms. Three different mechanisms have been proposed to explain the occurrence of heartburn in endoscopy-negative patients: esophageal visceral hypersensitivity, sustained esophageal contractions, and abnormal tissue resistance. Impaired esophageal mucosal resistance or increased sensitivity, even to small amounts of acid reflux, plays a key role in the pathophysiology of NERD. Moreover, hyperalgesia may be a predominant mechanism in eliciting symptoms in NERD patients. Increasingly seen are patients with a poor response to acid suppression treatment. Moreover, even double proton pump inhibitor dosing does not completely inhibit gastric acid secretion and relieve all symptoms. Thus, current definitions of acid reflux require review to increase the sensitivity to determine the frequency and implication of short periods of acidity in the esophagus. Analysis such as analysis of the area under the H+ activity time curve is one alternative approach for evaluating acid secretion. The precise role of acid in NERD needs further clarification.
SIMULTANEOUS DETERMINATION OF SULFAMETHOXAZOLE AND TRIMETHOPRIM IN PHARMACEUTICAL FORMULATIONS BY SQUARE WAVE VOLTAMMETRY

Objective: To develop a simple, fast and low-cost square wave voltammetric (SWV) method for simultaneous determination of sulfamethoxazole (SMX) and trimethoprim (TMP) using a glassy carbon electrode (GCE). Methods: The SWV parameters were optimized by 2 Results: Two well defined oxidation peaks were obtained at 0.96V (SMX) and 1.12V (TMP) in Britton–Robinson buffer (pH 6.0). Under optimized conditions, SWV measurements showed excellent linear response, ranging from 5.5x10 -5 to 3.95x10 -4 mol L -1 (R=0.9971) and 1.05x10 -5 to 1.04x10 -4 mol L -1 (R=0.9974) for SMX and TMP, respectively. The detection limits were found to be 8.52x10 -6 mol L -1 for SMX and 9.31x10 -7 mol L -1 for TMP. Conclusion: The proposed method was successfully applied to the determination of these antibiotics in commercial pharmaceutical formulations (tablets, oral suspension and injection), without any sample pretreatment. The obtained results are in good agreement with that obtained by the standard HPLC method at a 95% confidence level.
Uma sistemática para construção e escolha de modelos de previsão de risco de crédito

Com o aumento recente nos volumes de creditos a pessoas fisicas e, por consequencia, nos indices de inadimplencia, as empresas estao buscando melhorar sua analise de credito incorporando criterios objetivos. Tecnicas multivariadas tem sido utilizadas para construir modelos de previsao de credito que, baseados em informacoes cadastrais dos clientes, levam a criacao de um padrao de comportamento em relacao a inadimplencia. O objetivo deste artigo e propor uma sistematica para construcao de modelos de previsao de risco de credito e avaliar seu desempenho usando tres modelos especificos: analise discriminante, regressao logistica e redes neurais. O metodo proposto (denominado Modelo PRC) e composto de seis etapas: (i) delimitacao da populacao; (ii) selecao da amostra; (iii) analise preliminar; (iv) construcao do modelo; (v) escolha do modelo; e (vi) passos para implantacao. O Modelo PRC foi aplicado em uma amostra de 17.005 clientes de uma rede de farmacias com crediario proprio. Os resultados para este banco de dados especifico apontam uma pequena superioridade do modelo de redes neurais em relacao aos outros modelos, que pode ser atribuida a sua nao linearidade em relacao a combinacao de variaveis.
Porphyromonas gingivalis-Induced GEF Dock180 Activation by Src/PKCδ-Dependent Phosphorylation Mediates PLCγ2 Amplification in Salivary Gland Acinar Cells: Modulatory Effect of Ghrelin

Phospholipase Cγ2 (PLCγ2) plays a pivotal role in mediation of inflammatory reaction to bacterial lipopolysaccharide (LPS) as well as serves as a key target in modulatory influence of the hormone ghrelin. Here we explore the involvement of Rac1 and its activator, guanine nucleotide exchange factor (GEF), Dock180, in mediation of PLCγ2 activation in salivary gland acinar cells in response to P. gingivalis LPS and ghrelin. We show that stimulation of the acinar cells with the LPS leads to up-regulation in Dock and PLCγ2 activation, and is reflected in the membrane translocation of Rac1 and PLCγ2, while the effect of ghrelin is manifested by the suppression in Rac1 translocation. Further, we reveal that stimulation with the LPS leads to Dock180 phosphorylation on Tyr and Ser, while the modulatory influence of ghrelin, manifested by a drop in membrane Rac1-GTP, is asso-ciated with a distinct decrease in Dock180 phosphorylation on Ser. Moreover, we demonstrate that phosphorylation on Tyr remains under the control of Src kinase and is accompanied by Dock180 membrane translocation, while protein kinase Cδ(PKCδ) is involved in the LPS-induced phosphorylation of the membrane-recruited Dock180 on Ser. Thus, our findings underscore the role of Src/PKCδ-mediated GEF Dock180 phosphorylation on Tyr/Ser in modulation of salivary gland acinar cell PLCγ2 activation in response to P. gingivalis as well as ghrelin.
Meta-analysis: serious adverse events in Crohn's disease patients treated with TNF-alpha inhibitors.

BACKGROUND/AIMS It remains a question whether anti-TNF-a treatment is associated with an increase of serious adverse events (SAE) in Crohn's Disease (CD) patients. This study aims to assess the risk of SAE of anti-TNF-a treatment in CD patients. METHODOLOGY Literature search of EMBASE, PubMed, ScienceDirect, Cochrane Library and ClinicalTrials.gov until June 2012 was conducted. Eligible studies were randomized controlled trials (RCTs) ofTNF-a inhibitors treated for at least 24 weeks in CD patients. RESULTS Thirteen RCTs, involving 4,257 patients with CD were included in analysis. SAE were reported in 364 patients (14.26%) in treatment groups and 263 patients (15.43%) in control groups. The proportion of patients with SAE was lower with TNF-a inhibitors than with placebo (OR, 0.80; 95% CI, 0.67-0.96; p=0.01). Compared with controls, the risks of malignancy and serious infection treated with TNF-a inhibitors showed no significant difference (p>0.05). CONCLUSIONS In CD patients, anti-TNF-a treatment, especially for adalimumab, could decrease the incidence of SAE, without an increased risk of malignancy or serious infection. TNF-a inhibitors are safe in treatment of CD patients. To assess the risk of SAE, larger samples of randomized control trials with long term follow-up are needed.
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.

OBJECTIVES In order to select new drugs and to predict their in vitro activity against Mycobacterium avium complex (MAC), new quantitative structure-activity relationship (QSAR) models were developed. METHODS The activities against MAC of 29 structurally heterogeneous drugs were examined by means of linear discriminant analysis (LDA) and multilinear regression analysis (MLRA) by using topological indices (TI) as structural descriptors. In vitro antimycobacterial activities were determined by a broth microdilution method with 7H9 medium. RESULTS The topological model obtained successfully classifies over 80% of compounds as active or inactive; consequently, it was applied in the search for new molecules active against MAC. From among the selected candidates demonstrating in vitro activity, aflatoxin B1, benzalkonium chloride and pentamidine stand out, with MIC50s between 4 and 32 mg/L. CONCLUSION The method described in this work is able to select molecules active against MAC.
Validation of JCountPro software for efficient assessment of ionizing radiation-induced foci in human lymphocytes

Abstract Purpose: Ionizing radiation-induced foci (IRIF) known also as DNA repair foci represent the most sensitive and specific assay for assessing DNA double-strand break (DSB). IRIF are usually visualized and enumerated with the aid of fluorescence microscopy using antibodies to phosphorylated γH2AX and 53BP1. Although several approaches and software packages were developed for quantification of IRIF, not one of them was commonly accepted and inter-laboratory variability in the outputs was reported. In this study, JCountPro software was validated for IRIF enumeration in two independent laboratories. Materials and methods: Human lymphocytes were γ-irradiated at doses of 0, 2, 5, 10 and 50 cGy. The cells were fixed, permeabilized and IRIF were immunostained using appropriate antibodies. Cell images were acquired with automatic Metafer system. Endogenous and radiation-induced γH2AX and 53BP1 foci were enumerated using JCountPro. This analysis was performed from the same cell galleries by the researchers from two laboratories. Yield of foci was analyzed by either arithmetic mean (AM) value (foci/cell) or principal average (PA) derived from the approximation of foci distribution with Poisson statistics. Statistical analysis was performed using factorial ANOVA. Results: Enumeration of 53BP1, γH2AX and co-localized 53BP1/γH2AX foci by JCountPro was essentially the same between laboratories. IRIF were detected at all doses and linear dose response was obtained in the studied dose range. PA values from Poisson distribution fitted the data better as compared to AM values and were more powerful and sensitive for IRIF analysis than the AM values. All JCountPro data were confirmed by visual focus enumeration. Conclusions: We concluded that the JCountPro software was efficient in objectively enumerating IRIF regardless of an individual researcher’s bias and has a potential for usage in clinics and molecular epidemiology.
Pharmacokinetics and Tissue Distribution of the Stereoisomers of 4-Methylaminorex in the Rat

4-Methylaminorex, a potential psychostimulant drug of abuse, exists as four stereoisomers: cis-4R,5S, cis-4S,5R, trans-4S,5S, and trans-4R,5R, which were shown previously to possess stereospecific effects. This study characterized their pharmacokinetic and tissue distribution profiles, and metabolic turnover to norephedrine and norpseudoephedrine, in male Wistar rats. The rats received each isomer intravenously, intraperitoneally, or orally, followed by blood sample collection via cannula (pharmacokinetic study), or tissue sample collection at predetermined time points (tissue distribution study). The samples were analyzed for cis- and trans-isomers, and when appropriate for norephedrine and norpseudoephedrine, with gas chromatography/mass spectrometry. Trans-4S,5S-, cis-4R,5S-, and cis-4S,5R-isomers behaved comparably kinetically (volume of distribution 1.7-2.3 l/kg, distribution half-life 3.8-7.0 min, elimination half-life 35-42 min, and bioavailability 32-57% intraperitoneally or 4-16% orally), whereas trans-4R,5R-isomer differed from the others, with a longer elimination half-life (118-169 min) and higher bioavailability (100% intraperitoneally or 83% orally). The highest isomer concentrations were observed in the kidney followed most frequently by the liver, brain, muscle, and last by fat and blood. The elimination half-lives of the stereoisomers from the tissues were generally similar to those in blood. No pharmacologically significant amounts of norephedrine or norpseudoephedrine were detected in blood or the brain. In conclusion, differences between the stereoisomers of 4-methylaminorex in the pharmacokinetics and tissue distribution are described. However, these differences are not compatible with, and thus may not account for, the distinct behavioral and neurochemical effects of the stereoisomers demonstrated previously. Furthermore, metabolic turnover to norephedrine and norpseudoephedrine does not seem to contribute significantly to 4-methylaminorex pharmacology.
The regulation of tyrosine kinase signalling pathways by growth factor and G-protein-coupled receptors.

Research Communications Lack of association of G-protein f2and y2-subunit N-terminal fragments provides evidence against the coiled-coil model of subunit-fy assembly Differential calcium dependence in the activity of c-Jun kinase and mitogen-activated protein kinase by muscarinic acetylcholine receptors in rat la cells Evaluation of the use of the luciferase-reporter-gene system for gene-regulation studies involving cyclic AMP-elevating agents
Do romantic partners' responses to entry dyspareunia affect women's experience of pain? The roles of catastrophizing and self-efficacy.

INTRODUCTION Entry dyspareunia is a sexual health concern which affects about 21% of women in the general population. Characterized by pain provoked during vaginal penetration, introital dyspareunia has been shown by controlled studies to have a negative impact on the psychological well-being, sexual function, sexual satisfaction, and quality of life of afflicted women. Many cognitive and affective variables may influence the experience of pain and associated psychosexual problems. However, the role of the partner's cognitive responses has been studied very little. AIM The aim of the present study was to examine the associations between partners' catastrophizing and their perceptions of women's self-efficacy at managing pain on one side and women's pain intensity, sexual function, and sexual satisfaction on the other. METHODS One hundred seventy-nine heterosexual couples (mean age for women = 31, SD = 10.0; mean age for men = 33, SD = 10.6) in which the woman suffered from entry dyspareunia participated in the study. Both partners completed quantitative measures. Women completed the Pain Catastrophizing Scale and the Painful Intercourse Self-Efficacy Scale. Men completed the significant-other versions of these measures. MAIN OUTCOME MEASURES Dependent measures were women's responses to (i) the Pain Numeric Visual Analog Scale; (ii) the Female Sexual Function Index; and (iii) the Global Measure of Sexual Satisfaction scale. RESULTS Controlled for women's pain catastrophizing and self-efficacy, results indicate that higher levels of partner-perceived self-efficacy and lower levels of partner catastrophizing are associated with decreased pain intensity in women with entry dyspareunia, although only partner catastrophizing contributed unique variance. Partner-perceived self-efficacy and catastrophizing were not significantly associated with sexual function or satisfaction in women. CONCLUSIONS The findings suggest that partners' cognitive responses may influence the experience of entry dyspareunia for women, pointing toward the importance of considering the partner when treating this sexual health problem.
High performances supercapacitor recovery system for industrial drive applications

Recent developments in the field of supercapacitors make very promising the use of these equipments in a large range of applications. In particular, it is useful to introduce supercapacitors in all the drive applications, in which an energy recovery it is possible. In this paper, a predictive control of the supercapacitor storage system is proposed and tested in the field of the automatic warehouse. Experimental results show the increased performances of the systems thanks to supercapacitors energy recovery capability.
Substance abusers report being more alexithymic than others but do not show emotional processing deficits on a performance measure of alexithymia

Substance abusers report that they have deficits in emotional processing (“alexithymia”; Taylor et al. ), but is their actual emotional processing performance actually deficient? The prevalence of self-reported alexithymia in a group of newly abstinent substance abusers (N = 40) was 50%, which is considerably higher than that found in normal and psychiatric outpatient samples. However, the actual performance of this group on a task that required them to identify and describe feelings was not significantly different from either a group of university students (after controlling for IQ, age, and gender) or a normal group of adults. In addition, there was no relationship between self-reported and actual emotional processing performance, which is contrary to what has been found in a normal sample. Substance abusers believe they are more alexithymic than others, but do not perform as if they are so.
Probability and Risk: Foundations and Economic Implications of Probability-Dependent Risk Preferences

A large body of evidence has documented that risk preferences depend nonlinearly on outcome probabilities. We discuss the foundations and economic consequences of probability-dependent risk preferences and offer a practitioner's guide to understanding and modeling probability dependence. We argue that probability dependence provides a unifying framework for explaining many real-world phenomena, such as the equity premium puzzle, the long-shot bias in betting markets, and households' underdiversification and their willingness to buy small-scale insurance at exorbitant prices. Recent findings indicate that probability dependence is not just a feature of laboratory data, but is indeed manifest in financial, insurance, and betting markets. The neglect of probability dependence may prevent researchers from understanding and predicting important phenomena.
Information Analysis of a Spatial Database for Ecological Land classification

An ecological land classification was developed for a complex region in southern California using geographic information system techniques of map overlay and contingency table analysis. Land classes were identified by mutual information analysis of vegetation pattern in relation to other mapped environmental variables. The analysis was weakened by map errors, especially errors in the digital elevation data. Nevertheless, the resulting land classification was ecologically reasonable and performed well when tested with higher quality data from the region.