Miracle-dz/UniFAR-FTUs huggingface dataset:
Systemic CTLA-4 Blockade Ameliorates Glioma-Induced Changes to the CD4+ T Cell Compartment without Affecting Regulatory T-Cell Function

Purpose: Patients with malignant glioma suffer global compromise of their cellular immunity, characterized by dramatic reductions in CD4+ T cell numbers and function. We have previously shown that increased regulatory T cell (Treg) fractions in these patients explain T-cell functional deficits. Our murine glioma model recapitulates these findings. Here, we investigate the effects of systemic CTLA-4 blockade in this model. Experimental Design: A monoclonal antibody (9H10) to CTLA-4 was employed against well-established glioma. Survival and risks for experimental allergic encephalomyelitis were assessed, as were CD4+ T cell numbers and function in the peripheral blood, spleen, and cervical lymph nodes. The specific capacities for anti-CTLA-4 to modify the functions of regulatory versus CD4+CD25− responder T cells were evaluated. Results: CTLA-4 blockade confers long-term survival in 80% of treated mice, without eliciting experimental allergic encephalomyelitis. Changes to the CD4 compartment were reversed, as anti-CTLA-4 reestablishes normal CD4 counts and abrogates increases in CD4+CD25+Foxp3+GITR+ regulatory T cell fraction observed in tumor-bearing mice. CD4+ T-cell proliferative capacity is restored and the cervical lymph node antitumor response is enhanced. Treatment benefits are bestowed exclusively on the CD4+CD25− T cell population and not Tregs, as CD4+CD25− T cells from treated mice show improved proliferative responses and resistance to Treg-mediated suppression, whereas Tregs from the same mice remain anergic and exhibit no restriction of their suppressive capacity. Conclusions: CTLA-4 blockade is a rational means of reversing glioma-induced changes to the CD4 compartment and enhancing antitumor immunity. These benefits were attained through the conferment of resistance to Treg-mediated suppression, and not through direct effects on Tregs.
The Role of Doppler Echocardiography in the Assessment of Left Ventricular Diastolic Function

The role of Doppler echocardiography of transmitral filling velocities in the assessment of diastolic function in man has not been adequately defined. It is now appreciated that multiple interacting factors such as loading conditions influence the transmitral velocity profile independent of intrinsic left ventricular diastolic function. Extrapolating the status of diastolic function from the transmitral velocity profile is complicated by these factors. The load dependence of ventricular filling has tempered the initial enthusiasm for the clinical application of the Doppler technique. In the present review, studies examining invasive parameters of diastolic function and Doppler indices of diastolic filling are discussed to gain greater insight and understanding of the role of Doppler echocardiography in the noninvasive assessment of diastolic function. These studies have demonstrated a relatively consistent influence of left ventricular relaxation, chamber stiffness, and left atrial pressure on the transmitral velocity filling profile. Impairment of relaxation impedes early filling and may result in a compensatory increase in atrial contribution to filling. An independent decrease in left atrial pressure from altered loading conditions may also reduce filling in early diastole. Increased left ventricular chamber stiffness (i.e., noncompliant left ventricle) impairs atrial contribution to filling and may enhance early filling. Theoretically, reduced left atrial contractility may decrease atrial contribution to filling. Pulmonic vein flow demonstrating increased retrograde flow during atrial systole helps to exclude impaired left atrial contractility. An increased left atrial pressure from altered loading conditions may also augment early filling. Therefore, an invasive or clinical assessment of left atrial pressure as being increased, decreased, or normal greatly aids in the interpretation of the transmitral filling velocity profile when inferences on the status of diastolic function are being made. Diastolic dysfunction is likely when a given pattern of filling cannot be explained on the basis of left atrial pressure. In situations where reasonable estimates on the status of left atrial pressure cannot be done, striking alterations in the transmitral velocity filling profile may be useful.
Working time policy in France

Working time has always been considered in France to be an area of responsibility for the State. The Acts on the 35-hour working week come therefore from a long tradition of State intervention to regulate employment and working conditions. This particular configuration is not found in other European countries. In this paper is presented the French specificity: a work sharing logic supported by the State. The aim at generating employment through a legal reduction of working time brought the government to draw up an extremely complex set of Acts. These one are not restricted to defining legal work duration; they also advocate reductions in social contributions and give a precise framework to negotiate collective agreements. A synthesis of the consequences of the 35-hour Act shows that the effects on employment are limited (creation of 300,000 jobs), that social relations did not improve and that inequalities among employees were accentuated
Analysis of Gene Expression Data 10.1 Introduction 10.1.1 Motivation

A central goal of molecular biology is to understand the regulation of protein synthesis and its reactions to external and internal signals. All the cells in an organism carry the same genomic data, yet their protein makeup can be drastically different both temporally and spatially, due to regulation. One of the main junctions at which regulation occurs is mRNA transcription. A major role in this machinery is played by proteins themselves, that bind to regulatory regions along the DNA, greatly affecting the transcription of the genes they regulate. In order to get a " snapshot " of transcription levels of the genes within the cell we use DNA microarrays which measure the expression level for thousands of genes (the data matrix). An analysis of this data will give us some understanding on the key biological features of the cellular systems that produced it. One analysis approach is using clustering algorithms which attempt to locate group of genes that have similar expression patterns over a set of experiments (for more details see lecture notes 4-6). This approach has proven to be useful in discovering genes that are co-regulated. A more ambitious goal for analysis is revealing the structure of the transcriptional regulation process. This is clearly a hard problem. The current data is extremely noisy. Moreover, mRNA expression data alone only gives a partial picture that does not reflect key events such as translation and protein (in)activation. Finally, the amount of samples, even in the largest experiments in the foreseeable future, does not provide enough information to construct a full detailed model with high statistical significance. In this lecture, we describe another approach for analyzing gene expression patterns (based on the work of Friedman et al. [12]), that uncovers properties of the transcriptional program by examining statistical properties of dependence and conditional independence in the data based on Bayesian networks [24]. These networks represent the dependence structure between multiple interacting quantities by a graph-based model. Such models are attractive for their ability to describe complex stochastic processes, and for providing clear methodologies for learning from (noisy) observations.
Clinical Epidemiology and Molecular Analysis of Extended-Spectrum-β-Lactamase-Producing Escherichia coli in Nepal: Characteristics of Sequence Types 131 and 648

ABSTRACT Recently, CTX-M-type extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli strains have emerged worldwide. In particular, E. coli with O antigen type 25 (O25) and sequence type 131 (ST131), which is often associated with the CTX-M-15 ESBL, has been increasingly reported globally; however, epidemiology reports on ESBL-producing E. coli in Asia are limited. Patients with clinical isolates of ESBL-producing E. coli in the Tribhuvan University teaching hospital in Kathmandu, Nepal, were included in this study. Whole-genome sequencing of the isolates was conducted to analyze multilocus sequence types, phylotypes, virulence genotypes, O25b-ST131 clones, and distribution of acquired drug resistance genes. During the study period, 105 patients with ESBL-producing E. coli isolation were identified, and the majority (90%) of these isolates were CTX-M-15 positive. The most dominant ST was ST131 (n = 54; 51.4%), followed by ST648 (n = 15; 14.3%). All ST131 isolates were identified as O25b-ST131 clones, subclone H30-Rx. Three ST groups (ST131, ST648, and non-ST131/648) were compared in further analyses. ST648 isolates had a proportionally higher resistance to non-β-lactam antibiotics and featured drug-resistant genes more frequently than ST131 or non-ST131/648 isolates. ST131 possessed the most virulence genes, followed by ST648. The clinical characteristics were similar among groups. More than 38% of ESBL-producing E. coli isolates were from the outpatient clinic, and pregnant patients comprised 24% of ESBL-producing E. coli cases. We revealed that the high resistance of ESBL-producing E. coli to multiple classes of antibiotics in Nepal is driven mainly by CTX-M-producing ST131 and ST648. Their immense prevalence in the communities is a matter of great concern.
Complications and survival following radiologically and endoscopically-guided gastrostomy in patients with amyotrophic lateral sclerosis

In the natural progression of amyotrophic lateral sclerosis (ALS), a state of malnutrition often develops, associated with reduced oral intake, caused by difficulties with swallowing, adequate salivation, and/or anorexia. The placement of a feeding tube should be considered at the point where patients demonstrate swallowing difficulty and/or alteration in nutritional status. The goal of this prospective work was to compare, in 50 patients having definite or probable ALS, the complications after endoscopic (PEG), or radiologically-guided gastrostomy (RIG) and to evaluate their effects on survival. RIG was proposed as first-line therapy when patients had a slow vital capacity (SVC) less than 50% of the theoretical value, or in a case where PEG was refused by the patient. Thirty patients underwent PEG procedure, and 20 had RIG. Among the decisional criteria for placing a gastrostomy tube, risk of aspiration demonstrated by using videofluoroscopy was more frequently observed in the RIG group (65%) than in the PEG group (19.2%) (p=0.002). The two patient populations at time of gastrostomy placement were comparable with respect to age, gender ratio, disease duration before gastrostomy, the form and the gravity of neurological involvement as well as for nutritional criteria. The only significant difference observed between the two groups was the level of the SVC, much lower for patients undergoing RIG: 51.6±25.0% versus 67.4±26.7% than for the PEG group (p=0.03). The frequency of all complications observed at the moment of placement of gastrostomy tube and during the first month of follow-up was not significantly different between the two groups. Kaplan- Meier survival curves from the date of gastrostomy placement were not different in univariate analysis (p=0.85). In multivariate analysis, survival was not different between one group and the other (p=0.28). The major interest of the RIG technique rests on its greater feasibility and on the possibility of utilizing it in ALS patients who have significant ventilatory compromise.
Stimulation of the α7 nicotinic acetylcholine receptor protects against sepsis by inhibiting Toll-like receptor via phosphoinositide 3-kinase activation.

BACKGROUND The Toll-like receptor (TLR) plays an important role in the induction of the hyperinflammatory response and tissue injury in sepsis. The cholinergic antiinflammatory pathway serves as a link between the parasympathetic and innate immune systems. We examined the antiinflammatory effect of nicotine, a potent α7 nicotinic acetylcholine receptor (α7nAChR) agonist, with regard to TLR expression and signaling during sepsis. METHODS Polymicrobial sepsis was induced in mice by cecal ligation and puncture (CLP). The subjects received intraperitoneal nicotine (400 μg/kg) immediately after CLP for the biochemical study and 0, 24, 48, and 72 hours after CLP for the survival test. Intraperitoneal methyllycaconitine (MLA; 5 mg/kg), an α7nAChR antagonist, was administered 5 minutes prior to nicotine treatment. We evaluated the effects of nicotine using α7nAChR and phosphoinositide 3-kinase (PI3K) inhibitors in lipopolysaccharide-stimulated RAW264.7 cells. RESULTS Nicotine improved sepsis-induced mortality, attenuated organ failure, and suppressed inflammatory cytokines, which were abolished by MLA. Nicotine enhanced PI3K/Akt activation and reduced PU.1 activity and TLR4 expression. MLA and PI3K inhibitors blocked this effect of nicotine. CONCLUSIONS Our findings suggest that stimulation of the cholinergic antiinflammatory pathway by nicotine protects against septic injury and that this may be associated with inhibition of TLR4 expression via α7nAChR/PI3K signaling.
Crawling technology on eDonkey network and characteristics analysis

EDonkey network which had a large number of shared resources had become a popular P2P files sharing network. In order to analyzing the characteristics of eDonkey network, this paper provided a method which could prevent the crawler from being added to the blacklist of the server and could break the count restriction of the results when crawler searching something from the server. Then the paper summarized the server distribution characteristics and the distribution characteristics of the shared files.
Quantitative Trait Loci Affecting Rous Sarcoma Virus Induced Tumor Regression Trait in F 2 Intercross Chickens

We performed a genome-wide linkage and quantitative trait locus (QTL) analysis to confirm the existence of QTL affecting Rous Sarcoma Virus (RSV) induced tumor regression, and to estimate their effects on phenotypic variance in an F2 resource population. The F2 population comprised 158 chickens obtained by crossing tumor regressive White Leghorn (WL) and tumor progressive Rhode Island Red (RIR) lines was measured for tumor formation after RSV inoculation. Forty-three tumor progressive and 28 tumor regressive chickens were then used for genome-wide linkage and QTL analysis using a total of 186 microsatellite markers. Microsatellite markers were mapped on 20 autosomal chromosomes. A significant QTL was detected with marker LEI0258 located within the MHC B region on chromosome 16. This QTL had the highest F ratio (9.8) and accounted for 20.1% of the phenotypic variation. Suggestive QTL were also detected on chromosomes 4, 7 and 10. The QTL on chromosome 4 were detected at the 1% chromosome-wide level explaining 17.5% of the phenotypic variation, and the QTLs on chromosome 7 and 10 were detected at the 5% chromosome-wide level and explained 11.1% and 10.5% of the phenotypic variation, respectively. These results indicate that the QTLs in the non-MHC regions play a significant role in RSV-induced tumor regression. The present study constitutes one of the first preliminary reports in domestic chickens for QTLs affecting RSV-induced tumor regression outside the MHC region. (
Developmental changes in Ca2+/calmodulin-dependent protein kinase II in cultures of hippocampal pyramidal neurons and astrocytes

We have analyzed Ca2+/calmodulin-dependent protein kinase II (CaM- kinase II) localization, activity, and endogenous protein substrates during differentiation and synaptogenesis in cultured hippocampal neurons. Primary cultures from hippocampi from 18 d embryonic rats are composed primarily of pyramidal neurons, with minimal contamination by nonneuronal cells. We have used monoclonal (Mab) and affinity-purified polyclonal antibodies that recognize either or both of the subunits of CaM-kinase II in order to localize the enzyme at progressive stages of neuronal differentiation. Diffuse but specific binding, determined by indirect immunofluorescence analyses, was first detected in cell bodies and growth cones of pyramidal neurons after 4 d in culture. Immunoreactivity increased during the next 3 d of culture, at which time fluorescent, labeling was patchy along neuritic processes. By 10 d, intensely fluorescent, discrete spots were observed along processes and on cell bodies. Astrocyte cultures prepared from newborn rat cortex showed no detectable immunofluorescence with anti-CaM-kinase II antibodies. Cytosolic and particulate fractions from cultured pyramidal neurons and astrocytes were analyzed using immunoblot, in vitro phosphorylation, 2-dimensional gel electrophoresis, and phosphopeptide mapping techniques. Although pure astrocyte cultures contained low levels of Ca2+/CaM-stimulated protein kinase activity, they did not display detectable levels of immunoreactive 50 kDa subunit nor 50 and 60 kDa phosphoproteins analogous to the autophosphorylated subunits of CaM-kinase II. Immunoblot analysis detected the 60 kDa kinase subunit in particulate and cytosolic fractions from 2 d neurons. By contrast, the 50 kDa subunit of CaM-kinase II was not detected in cytosolic or particulate fractions of pyramidal neurons before 4 d in culture. In 2 d pyramidal neuron cultures, only low levels of Ca2+/CaM-stimulated protein phosphorylation were observed. Ca2+/CaM-dependent phosphorylation of 10 d pyramidal cell proteins was 3–5-fold greater than that of 2 d cultures, and included major phosphoproteins of 48, 50, 56, 58/60, 80–86, 90, 120, 138, 175, and 190 kDa. Phosphopeptide maps of 58/60 and 50 kDa phosphoproteins gave patterns very similar to those of the autophosphorylated 60 and 50 kDa subunits, respectively, of purified CaM-kinase II. A phosphoprotein doublet of 83 kDa was identified as synapsin I. Developmental changes in Ca2+/CaM-dependent phosphorylation in pyramidal neuron cultures were very similar to those previously described in subcellular fractions from postnatal rat forebrain.
Quality aware query scheduling in wireless sensor networks

We study query scheduling in Wireless Sensor Networks (WSNs) with a focus on two important metrics: Quality of Service (QoS) and Quality of Data (QoD). The motivation comes from our observation that most WSN scheduling techniques ignore the quality requirements of queries. As a result, they are inefficient or inapplicable to quite a few applications that have different quality requirements. In this paper, we propose a distributed Quality Aware Scheduling (QAS) framework to address this problem. QAS works on top of existing quality-unaware query scheduling protocols and allows individual users to specify their QoS and QoD requirements on their queries. Given these quality requirements, QAS determines the target qualities to be provided in scheduling and the execution order of these queries so as to maximize the total system profit. Our preliminary results show that QAS significantly outperforms the baseline scheduling algorithms in terms of system profit.
Shy1p is necessary for full expression of mitochondrial COX1 in the yeast model of Leigh's syndrome

SHY1 codes for a mitochondrial protein required for full expression of cytochrome oxidase (COX) in Saccharomyces cerevisiae. Mutations in the homologous human gene (SURF1) have been reported to cause Leigh's syndrome, a neurological disease associated with COX deficiency. The function of Shy1p/Surf1p is poorly understood. Here we have characterized revertants of shy1 null mutants carrying extragenic nuclear suppressor mutations. The steady‐state levels of COX in the revertants is increased by a factor of 4–5, accounting for their ability to respire and grow on non‐fermentable carbon sources at nearly wild‐type rates. The suppressor mutations are in MSS51, a gene previously implicated in processing and translation of the COX1 transcript for subunit 1 (Cox1) of COX. The function of Shy1p and the mechanism of suppression of shy1 mutants were examined by comparing the rates of synthesis and turnover of the mitochondrial translation products in wild‐type, mutant and revertant cells. We propose that Shy1p promotes the formation of an assembly intermediate in which Cox1 is one of the partners.
The risk of diabetes development in long-term observation of patients with acute hyperglycaemia during myocardial infarction.

BACKGROUND Acute hyperglycemia in patients with myocardial infarction is an unfavorable predictive factor. However, there are limited data regarding the relationship between acute hyperglycemia and the incidence of new onsets diabetes in long-term observation. AIM We studied the relationship between admission glycemia in patients with myocardial infarction and the future development of diabetes. METHODS In 190 patients admitted during 2004-2007 years with myocardial infarction diabetes was excluded on the basis of oral glucose tolerance test (OGTT) performed at the end of hospitalization. Patients were divided into three groups according to admission glucose level: G1 <7.8 mmol/l (<140 mg/dl); G2: 7.8-11.0 mmol/l (140-199 mg/dl); G3 ≥11.1 mmol/l (≥200 mg/dl). RESULTS The groups consisted of 80 (42.1%), 94 (49.5%) and 16 (8.4%) patients, respectively for G1, G2 and G3. The mean age was 61.3±11.3 years. ST-segment elevation myocardial infarction (STEMI) was diagnosed in 158 patients (83.2%) and non-ST-segment elevation myocardial infarction (NSTEMI) in 32 patients (16.8%). A total of 15 cases (7.9% of the study group) of newly diagnosed diabetes mellitus were registered during a mean follow-up of 48.2±13.9 months. Higher incidence of new diabetes diagnosis was noticed in patients with higher glucose level on admission (5.0% vs. 7.4% vs. 25.0%, p=0.0249). Regression analysis showed two independent risk factors of diabetes development in observational period: admission glucose level considered as continuous variable with OR 1.2 (95% CI 1.0-1.4, p=0.03) and occurrence of IGT with OR 3.6 (95% CI 1.0-12.0, p=0.04). CONCLUSIONS Patients with acute hyperglycemia during myocardial infarction are more likely to have diabetes in future. This group of patients requires a close monitoring of glucose metabolism after myocardial infarction.
Electrophysiological Evidence of the Capture of Visual Attention

The presence of a salient distractor interferes with visual search. According to the salience-driven selection hypothesis, this interference is because of an initial deployment of attention to the distractor. Three event-related potential (ERP) findings have been regarded as evidence for this hypothesis: (a) salient distractors were found to elicit an ERP component called N2pc, which reflects attentional selection; (b) with target and distractor on opposite sides, a distractor N2pc was reported to precede the target N2pc (N2pc flip); (c) the distractor N2pc on slow-response trials was reported to occur particularly early, suggesting that the fastest shifts of attention were driven by salience. This evidence is equivocal, however, because the ERPs were noisy (b, c) and were averaged across all trials, thereby making it difficult to know whether attention was deployed directly to the target on some trials (a, b). We reevaluated this evidence using a larger sample size to reduce noise and by analyzing ERPs separately for fast- and slow-response trials. On fast-response trials, the distractor elicited a contralateral positivity (PD)-an index of attentional suppression-instead of an N2pc. There was no N2pc flip or early distractor N2pc. As it stands, then, there is no ERP evidence for the salience-driven selection hypothesis.