Miracle-dz/UniFAR-FTUs huggingface dataset:
Bcl6 Controls the Th2 Inflammatory Activity of Regulatory T Cells by Repressing Gata3 Function

The transcriptional repressor Bcl6 is a critical arbiter of Th cell fate, promoting the follicular Th lineage while repressing other Th cell lineages. Bcl6-deficient (Bcl6−/−) mice develop a spontaneous and severe Th2-type inflammatory disease, thus warranting assessment of Bcl6 in regulatory T cell (Treg) function. Bcl6−/− Tregs were competent at suppressing T cell proliferation in vitro and Th1-type colitogenic T cell responses in vivo. In contrast, Bcl6−/− Tregs strongly exacerbated lung inflammation in a model of allergic airway disease and promoted higher Th2 responses, including systemic upregulation of microRNA-21. Further, Bcl6−/− Tregs were selectively impaired at controlling Th2 responses, but not Th1 and Th17 responses, in mixed chimeras of Bcl6−/− bone marrow with Foxp3−/− bone marrow. Bcl6−/− Tregs displayed increased levels of the Th2 transcription factor Gata3 and other Th2 and Treg genes. Bcl6 potently repressed Gata3 transcriptional transactivation, providing a mechanism for the increased expression of Th2 genes by Bcl6−/− Tregs. Gata3 has a critical role in regulating Foxp3 expression and functional fitness of Tregs; however, the signal that regulates Gata3 and restricts its transactivation of Th2 cytokines in Tregs has remained unexplored. Our results identify Bcl6 as an essential transcription factor regulating Gata3 activity in Tregs. Thus, Bcl6 represents a crucial regulatory layer in the Treg functional program that is required for specific suppression of Gata3 and Th2 effector responses by Tregs.
Sobre o comportamento de agentes racionais em redes complexas

O avanco constante dos sistemas de informacao permite, a uma taxa de crescente, que mais dados sejam gerados e armazenados. A partir das mais rotineiras situacoes, tais como con-versas telefonicas, a atuacao de sistemas tecnologicos de alta complexidade, tais como redes de sensores sem fio (RSSF) para detectar eventos climaticos, dados sao gerados e armazena-dos registrando cada acao e decisao tomada pelos agentes desses sistemas. E fascinante que, por tras desses registros, vemos o reflexo do ambiente em si, ja que por tras de cada registro, ha uma decisao tomada por alguma entidade. Portanto, o conhecimento de como processar esse valioso banco de dados em evolucao pode levar, consequentemente, para uma melhor compreensao dos interesses e da dinâmica de cada entidade em um determinado ambiente ou na sociedade. Nesta tese, nos concentramos em sistemas que sao compostos de entidades (individuos, organizacoes e sistemas computacionais), capazes de interagir entre si de uma maneira racional, refletindo seus interesses e dinâmica de atividade. Nos chamamos esses sistemas de Redes Complexas Baseadas em Decisao (RCBD), estes individuos e/ou organizacoes, nosou agentes, e as interacoes entre nos, arestas. A principal caracteristica de uma RCBD e que ela evolui de acordo com as motivacoes pessoais dos seus nos. Portanto, o objetivo principal desta tese e analisar o comportamento dos agentes de uma RCBD. Pretendemos observarcenarios reais e hipoteticos, onde as decisoes tem um papel importante na evolucao da rede. Quando compreendemos plenamente as motivacoes por tras das acoes dos agentes, podere-mos modelar, prever e controlar o seu comportamento. Dividimos o objetivos principal desta tese em tres objetivos especificos: (i) Modelagem, em que o nosso objetivo e representar fielmente o comportamento dos agentes em uma RCBD; (ii) Predicao, em que o nosso ob-jetivo e prever como evoluira o sistema, e (iii) Controle, em que o nosso objetivo e criarmecanismos para fazer os agentes agirem de acordo com um objetivo determinado. Em primeiro lugar, analisamos as redes de comunicacao formada a partir de registros telefonicos de um operadora movel privada de uma grande cidade. Propomos modelos para o comportamento individual dos usuarios dessa rede e, a partir disso, propomos aplicacoes para reducao de dados, deteccao de anomalias e monitoramento de rede. Entao, analisamos redes competitivas formadas a partir de ligas esportivas, como a liga profissional de basquete americana (NBA) e a liga profissional de baseball (MLB). Propomos modelos de previsao que podem ser usados para identificar as equipes mais provaveis para ganhar a temporada seguinte. Finalmente, investigamos a tomada de decisoes em redes de computadores, em um cenario onde um grupo de RSSFs sao implantados na mesma regiao e elas podem interagir entre elas para solicitar ou compartilhar recursos computacionais. Nos modelamos o prob-lema da cooperacao entre duas ou mais RSSFs diferentes pelos conceitos da teoria dos jogos e com isso nos apresentamos, como uma aplicacao de controle, um protocolo para permitir a cooperacao entre eles.
Bacterial Production, Characterization and Protein Modeling of a Novel Monofuctional Isoform of FAD Synthase in Humans: An Emergency Protein?

FAD synthase (FADS, EC 2.7.7.2) is the last essential enzyme involved in the pathway of biosynthesis of Flavin cofactors starting from Riboflavin (Rf). Alternative splicing of the human FLAD1 gene generates different isoforms of the enzyme FAD synthase. Besides the well characterized isoform 1 and 2, other FADS isoforms with different catalytic domains have been detected, which are splice variants. We report the characterization of one of these novel isoforms, a 320 amino acid protein, consisting of the sole C-terminal 3′-phosphoadenosine 5′-phosphosulfate (PAPS) reductase domain (named FADS6). This isoform has been previously detected in Riboflavin-Responsive (RR-MADD) and Non-responsive Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) patients with frameshift mutations of FLAD1 gene. To functionally characterize the hFADS6, it has been over-expressed in Escherichia coli and purified with a yield of 25 mg·L−1 of cell culture. The protein has a monomeric form, it binds FAD and is able to catalyze FAD synthesis (kcat about 2.8 min−1), as well as FAD pyrophosphorolysis in a strictly Mg2+-dependent manner. The synthesis of FAD is inhibited by HgCl2. The enzyme lacks the ability to hydrolyze FAD. It behaves similarly to PAPS. Combining threading and ab-initio strategy a 3D structural model for such isoform has been built. The relevance to human physio-pathology of this FADS isoform is discussed.
Induction of Cell Cycle Arrest and Morphological Differentiation by Nurr1 and Retinoids in Dopamine MN9D Cells*

Dopamine cells are generated in the ventral midbrain during embryonic development. The progressive degeneration of these cells in patients with Parkinson's disease, and the potential therapeutic benefit by transplantation of in vitrogenerated dopamine cells, has triggered intense interest in understanding the process whereby these cells develop. Nurr1 is an orphan nuclear receptor essential for the development of midbrain dopaminergic neurons. However, the mechanism by which Nurr1 promotes dopamine cell differentiation has remained unknown. In this study we have used a dopamine-synthesizing cell line (MN9D) with immature characteristics to analyze the function of Nurr1 in dopamine cell development. The results demonstrate that Nurr1 can induce cell cycle arrest and a highly differentiated cell morphology in these cells. These two functions were both mediated through a DNA binding-dependent mechanism that did not require Nurr1 interaction with the heterodimerization partner retinoid X receptor. However, retinoids can promote the differentiation of MN9D cells independently of Nurr1. Importantly, the closely related orphan receptors NGFI-B and Nor1 were also able to induce cell cycle arrest and differentiation. Thus, the growth inhibitory activities of the NGFI-B/Nurr1/Nor1 orphan receptors, along with their widespread expression patterns both during development and in the adult, suggest a more general role in control of cell proliferation in the developing embryo and in adult tissues.
Retrospective analysis of the outcome of patients with idiopathic inflammatory myopathy: a long-term follow-up study.

OBJECTIVES Several factors have been implicated in the prognosis of idiopathic inflammatory myopathies, including age, gender, delay in diagnosis, neoplasia, creatine kinase levels and some autoantibodies. We have reviewed the main factors contributing to mortality in patients with idiopathic inflammatory myopathy (IIM) diagnosed between 1976 and 2007 who were followed for at least 5 years in the Rheumatology Unit at University College Hospital in London. METHODS An observational retrospective study was carried out on patients with IIM diagnosed between 1976 and 2007. All the patients fullfilled at least three out of four of the Bohan and Peter criteria. The subjects were divided into the following groups: adult-onset polymyositis (APM); adult-onset dermatomyositis (ADM); juvenile dermatomyositis (JDM); Overlap syndromes with another autoimmune rheumatic disease. RESULTS 90 patients were identified. The female to male ratio was 2.5:1 and the mean age at diagnosis was 38.5 years (SD 15.03). 47.8% of the patients had APM, 30% adult-onset ADM, 15.6% Overlap and 6.7% JDM. Among the extramuscular features, 18.9% had pulmonary involvement. In 70% the highest CK was >5 times the upper normal. Prednisolone was prescribed in 98.9%. 11.1% received rituximab. 34.4% had monophasic, 31.1% relapsing and remitting and 34.4% continuous progressive course of the disease. The median follow-up was 11.5 years (IQR 12.00). 14.4% of the patients died, 30.8% due to infection, 30.8% from a cardiovascular event and 23.1% due to neoplasia. The 1, 5 and 10-year survival was 100%, 97.8% and 91%, respectively. Male gender (Hazards Ratio (HR) 3.222; p=0.037), pulmonary involvement (HR 5.247; p=0.009), chronic progressive course (HR 3.711; p=0.030) and use of rituximab (HR 3.562; p=0.036) were the only risk factors to be statistically significantly associated (p<0.05) with death. CONCLUSIONS We conclude that long-term survival in these patients is generally quite good with an estimated 10-year survival >90% in our cohort, which is even higher than previously reported.
Quercetin Potentiates L-Dopa Reversal of Drug-Induced Catalepsy in Rats: Possible COMT/MAO Inhibition

L-Dopa plus carbidopa treatment remains the first-line therapy in Parkinson’s disease. The use of catechol-O-methyltransferase (COMT) and/or monoamine oxidase (MAO) inhibitors as an adjunct to L-dopa therapy has yielded varying degrees of success. Quercetin, a flavonoid present in many plants, is reported to inhibit COMT and MAO activities, the key enzymes involved in the metabolism of dopamine. In the present study we have studied the effect of quercetin on the L-dopa plus carbidopa combination against perphenazine and reserpine-induced catalepsy in rats. Neuroleptic-induced catalepsy is a widely accepted animal model for testing the drugs used in parkinsonism. Catalepsy in rats was induced by administration of perphenazine (5 mg/kg i.p.) or reserpine (2.5 mg/kg i.p.) + α-methyl-p-tyrosine (200 mg/kg i.p.). Catalepsy in animals was assessed by using the bar test. The quercetin dose (25–100 mg/kg, p.o.) dependently reversed perphenazine- as well as reserpine-induced catalepsy. When quercetin was combined with a subthreshold dose of L-dopa plus carbidopa, the anticatatonic effect was potentiated. Pretreatment with a central COMT inhibitor, 3,5-dinitrocatechol (OR-486) (10 mg/kg p.o.), or a MAO-B inhibitor, selegiline (5 mg/kg i.p.), also potentiated the actions of threshold dose of quercetin against perphenazine- or reserpine-induced catalepsy. On the other hand adenosine (100 mg/kg i.p.), which is known to decrease the release of catecholamines through an action on presynaptic A1 receptors, partly reversed the protective effect of quercetin against perphenazine-induced catalepsy. Quercetin through its COMT and MAO enzyme-inhibiting properties might potentiate the anticatatonic effect of L-dopa plus carbidopa treatment. The results of the present study strongly suggest that quercetin could serve as an effective adjunct to L-dopa therapy in Parkinson’s disease.
The effect of model order selection in group PICA

Independent component analysis (ICA) of functional MRI data is sensitive to model order selection. There is a lack of knowledge about the effect of increasing model order on independent components' (ICs) characteristics of resting state networks (RSNs). Probabilistic group ICA (group PICA) of 55 healthy control subjects resting state data was repeated 100 times using ICASSO repeatability software and after clustering of components, centrotype components were used for further analysis. Visual signal sources (VSS), default mode network (DMN), primary somatosensory (S1), secondary somatosensory (S2), primary motor cortex (M1), striatum, and precuneus (preC) components were chosen as components of interest to be evaluated by varying group probabilistic independent component analysis (PICA) model order between 10 and 200. At model order 10, DMN and VSS components fuse several functionally separate sources that at higher model orders branch into multiple components. Both volume and mean z‐score of components of interest showed significant (P < 0.05) changes as a function of model order. In conclusion, model order has a significant effect on ICs characteristics. Our findings suggest that using model orders ≤20 provides a general picture of large scale brain networks. However, detection of some components (i.e., S1, S2, and striatum) requires higher model order estimation. Model orders 30–40 showed spatial overlapping of some IC sources. Model orders 70 ± 10 offer a more detailed evaluation of RSNs in a group PICA setting. Model orders > 100 showed a decrease in ICA repeatability, but added no significance to either volume or mean z‐score results. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Ondansetron Use in Pregnancy

The American College of Obstetricians and Gynecologists recommends early treatment of nausea and vomiting of pregnancy to stop progression to hyperemesis gravidarum. Nausea and vomiting and hyperemesis gravidarum typically occur during the first trimester, the sensitive time for exposure to teratogens because organogenesis is occurring in the embryo. An efficacious treatment used widely across the United States for both nausea and vomiting of pregnancy and hyperemesis gravidarum is ondansetron. Recent studies have provided conflicting findings on the safety of ondansetron during pregnancy. There are numerous limitations in the current literature on ondansetron safety including exposure to the medication is not limited to sensitive windows of organogenesis, there is a lack of information on dosing and compliance, self-reports of exposure are commonly used, an inadequate accounting exists for other factors that may explain the relationship between ondansetron exposure and the adverse outcome, and there exists a lack of biologic plausibility by which ondansetron might cause harm. It is the authors' opinion that current data do not support a reluctance to treat women with ondansetron in clinical practice.
Psychiatric intensive care in acute psychosis

We have reviewed the development of psychiatric intensive care, focusing on organizational factors and the causes of psychiatric violence, suggesting guidelines for rapid tranquillization. The economics of running a psychiatric intensive care unit were subjected to an analysis of fixed, semi-fixed and variable costs. Variable costs (treatment and patient numbers) were shown to be more open to manipulation and possible cost savings.
A new texture approach to discrimination of forest clearcut, canopy, and burned area using airborne C-band SAR

In this paper, we review some of ways in which texture classification has been handled in the image processing literature and introduce additional texture measures, namely, structure features. The equations that define a set of two measures of structure features are given. One of them relates to the structure component of the image. Another characterizes the structure complexity that occurs in the image. The impact of the variations of structure feature on classification accuracy is checked by a stepwise regression method. A comparison of performance is made between structure features and Haralick's features, extracted from the graylevel co-occurrence. The results suggest that structure features have discriminatory power in forest cover classification. Compared with Haralick's feature measures, structure feature measures minimize internal calculations within windows and are relatively simple. The outcome of structure feature measures need not be standardized. This gives a "unit-free" measure and "naturally occurring" groupings of objects. In combination with a classifier, structure feature measures are a significant extension over conventional texture feature measures.
Recurrent Relational Networks

This paper is concerned with learning to solve tasks that require a chain of interdependent steps of relational inference, like answering complex questions about the relationships between objects, or solving puzzles where the smaller elements of a solution mutually constrain each other. We introduce the recurrent relational network, a general purpose module that operates on a graph representation of objects. As a generalization of Santoro et al. [2017]'s relational network, it can augment any neural network model with the capacity to do many-step relational reasoning. We achieve state of the art results on the bAbI textual question-answering dataset with the recurrent relational network, consistently solving 20/20 tasks. As bAbI is not particularly challenging from a relational reasoning point of view, we introduce Pretty-CLEVR, a new diagnostic dataset for relational reasoning. In the Pretty-CLEVR set-up, we can vary the question to control for the number of relational reasoning steps that are required to obtain the answer. Using Pretty-CLEVR, we probe the limitations of multi-layer perceptrons, relational and recurrent relational networks. Finally, we show how recurrent relational networks can learn to solve Sudoku puzzles from supervised training data, a challenging task requiring upwards of 64 steps of relational reasoning. We achieve state-of-the-art results amongst comparable methods by solving 96.6% of the hardest Sudoku puzzles.
Pharmacokinetic evaluation of a new oral sustained release dosage form of tramadol.

AIMS To compare the pharmacokinetic profile of a new modified release formulation of tramadol (Tramadol LP 200 mg, SMB Technology, Marche-en-Famenne, Belgium) with that of an immediate release capsule (Topalgic) 50 mg, Grünenthal, Aachen, Germany) after single and multiple dosing and to assess the potential effect of food on its relative bioavailability. METHODS The first study had an open, single-dose, three-treatment, three-period, six-sequence, randomised, crossover design with at least a five-day wash-out. The second study had an open, steady-state, two-treatment, two-period, two-sequence, randomised crossover design with at least a seven-day wash-out. Both studies contained 30 healthy subjects. Both enantiomers of tramadol and O-demethyl-tramadol (the only active metabolite of tramadol) were assayed in the plasma using an LC-MS/MS method. AUC infinity, AUCt, Cmax, Tmax, and T1/2 were estimated. Statistical analysis was performed using univariate anova, the Wilcoxon nonparametric method or Friedman's nonparametric anova where appropriate. RESULTS Tramadol had a significantly lower Cmax and longer Tmax than the conventional formulation. Thus, the mean (+/- sd) Cmax of tramadol were 646 +/- 192 and 300 +/- 94 ng ml-1 for Topalgic 4 x 50mg and Tramadol LP 200 mg, respectively (95% confidence interval on the difference expressed as a percentage 42-51). AUC of tramadol from both formulations was comparable (similar AUC infinity and AUCt). Thus, the mean AUC infinity of (+/-)tramadol obtained after multiple dosing were 4611 +/- 1944 and 5105 +/- 2101 ngh ml-1 after Topalgic 4 x 50mg and Tramadol LP 200 mg, respectively (95%CI 102-123%). We also demonstrate that the pharmacokinetics of the drug are not influenced by the intake of food. Thus, the mean AUC infinity of (+/-) tramadol were 5444 +/- 1637 and 5169 +/- 1580 ngh ml-1 after Tramadol LP 200 mg given in the fasting and fed states, respectively (95%CI = 88-103%). CONCLUSIONS The new sustained release form of tramadol exhibits adequate properties for once a day administration. Furthermore, its pharmacokinetic profile is not affected by the intake of food.
Use of molecular typing methods to trace the dissemination of Listeria monocytogenes in a shrimp processing plant

Molecular typing of bacteria has been widely used in epidemiological studies but not as extensively for tracing the transmission of pathogenic bacteria in food plants. This study was conducted to examine the potential use of two molecular typing methods, random amplified polymorphic DNA (RAPD) analysis and pulsed-field gel electrophoresis (PFGE), to trace Listeria monocytogenes contamination in a shrimp processing plant. Ribotyping and phase typing were also performed on a select number of strains. One hundred fifteen strains of L. monocytogenes collected in different areas of a shrimp processing plant were first serotyped and then subtyped by molecular typing. RAPD and PFGE showed great promise for typing L. monocytogenes isolates since distinguishable and reproducible DNA polymorphisms were obtained. When the composite profile from both (RAPD and PFGE) methods was generated, there was an increase in the discriminatory power to discern differences between strains of L. monocytogenes. The results indicated that environmental strains all fell into composite profile groupings unique to the environment, while strains from both water and utensils shared another composite profile group. L. monocytogenes fresh shrimp isolates belonging to one profile group were found in different areas of the processing line. This same profile group was also present in food handlers from the processing and packaging areas of the plant.
Rapid screening for B19 parvovirus DNA in clinical specimens with a digoxigenin-labeled DNA hybridization probe

A rapid dot blot hybridization assay for the detection of B19 parvovirus DNA in human sera was developed. Small portions of four serum samples were mixed, filtered onto a nylon membrane, and hybridized with a digoxigenin-labeled DNA probe; for each membrane, 380 serum samples could be tested. When a dot was positive by the hybridization assay, the four serum samples dotted together were separately tested to identify the sample positive for B19 DNA. A total of 10,150 serum samples submitted for viral serological and laboratory investigation with no specific requests for B19 testing were analyzed. Nine serum samples were positive for B19 DNA by dot blot hybridization assay, and the results were confirmed by electron microscopy. This method has proven to be reliable, economical in terms of time and costs, and useful for large-scale screening of clinical specimens, both for diagnostic work and for a source of antigen.