Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationship between IL‐2 receptor expression and proliferative responses in lymphocytes from HIV‐1 seropositive homosexual men

Previous studies have shown that exogenous IL‐2 does not correct the reduction in phytohaemagglu‐tinin (PHA)‐induced proliferation of lymphocytes from HIV‐1 infected (HIV+) individuals. We investigated the mechanism of this reduction to determine if reduced expression of the complete IL‐2 receptor (IL‐2R) was responsible. In a series of experiments, PHA‐stimulated lymphocytes from a total of 89 HIV− and 93 HIV+ homosexual men from the Baltimore Multicentre AIDS Cohort Study (MACS) were studied to determine the expression of messages for the α and β subunits of the IL‐2R, the binding of 125I‐IL‐2 to high affinity IL‐2R, and the effect of IL‐2 on cell proliferation. Compared to HIV− donors, PHA‐stimulated lymphocytes from most HIV+ donors demonstrated (i) a reduction in high affinity IL‐2R expression that correlated with the reduction in the IL‐2‐induced proliferative response; and (ii) a reduction in expression of both IL‐2R α‐ and β‐chain mRNA which may be responsible for decreased high affinity IL‐2R expression. However, lymphocytes from some HIV+ individuals had borderline low IL‐2‐induced proliferation despite normal or elevated expression of high affinity IL‐2R. These results suggest that decreased expression of IL‐2R may account, at least in part, for the lower proliferative response of cells from HIV+ donors.
Temporal association between hospitalization and rate of falls after discharge.

BACKGROUND Evidence suggests that acute illness and hospitalization may increase the risk for falls. OBJECTIVE To evaluate the rate of falls, and associated risk factors, for 90 days following hospital discharge. METHODS We consecutively enrolled 311 patients, aged 65 years and older, discharged from the hospital after an acute medical illness and receiving home-nursing services. Patients were assessed within 5 days of discharge for prehospital and current functioning by self-report, and balance, vision, cognition, and delirium by objective measures. Patients were followed up weekly for 13 weeks for falls, injuries, and health care use. RESULTS The rate of falls was significantly higher in the first 2 weeks after hospitalization (8.0 per 1000 person-days) compared with 3 months later (1.7 per 1000 person-days) (P =.002). Fall-related injuries accounted for 15% of all hospitalizations in the first month after discharge. Independent prehospital risk factors significantly associated with falls included dependency in activities of daily living, use of a standard walker, 2 or more falls, and more hospitalizations in the year prior. Posthospital risk factors included use of a tertiary amine tricyclic antidepressant, probable delirium, and poorer balance, while use of a cane was protective. CONCLUSIONS The rate of falls is substantially increased in the first month after medical hospitalization, and is an important cause of injury and morbidity. Posthospital risk factors may be potentially modifiable. Efforts to assess and modify risk factors should be integral to the hospital and posthospital care of older adults (those aged >/=65 years).
Profiling Humoral Immune Responses to Clostridium difficile-Specific Antigens by Protein Microarray Analysis

ABSTRACT Clostridium difficile is an anaerobic, Gram-positive, and spore-forming bacterium that is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhea. Several studies have reported associations between humoral immunity and the clinical course of C. difficile infection (CDI). Host humoral immune responses are determined using conventional enzyme-linked immunosorbent assay (ELISA) techniques. Herein, we report the first use of a novel protein microarray assay to determine systemic IgG antibody responses against a panel of highly purified C. difficile-specific antigens, including native toxins A and B (TcdA and TcdB, respectively), recombinant fragments of toxins A and B (TxA4 and TxB4, respectively), ribotype-specific surface layer proteins (SLPs; 001, 002, 027), and control proteins (tetanus toxoid and Candida albicans). Microarrays were probed with sera from a total of 327 individuals with CDI, cystic fibrosis without diarrhea, and healthy controls. For all antigens, precision profiles demonstrated <10% coefficient of variation (CV). Significant correlation was observed between microarray and ELISA in the quantification of antitoxin A and antitoxin B IgG. These results indicate that microarray is a suitable assay for defining humoral immune responses to C. difficile protein antigens and may have potential advantages in throughput, convenience, and cost.
Metformin and temozolomide, a synergic option to overcome resistance in glioblastoma multiforme models

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor survival. Cytoreduction in association with radiotherapy and temozolomide (TMZ) is the standard therapy, but response is heterogeneous and life expectancy is limited. The combined use of chemotherapeutic agents with drugs targeting cell metabolism is becoming an interesting therapeutic option for cancer treatment. Here, we found that metformin (MET) enhances TMZ effect on TMZ-sensitive cell line (U251) and overcomes TMZ-resistance in T98G GBM cell line. In particular, combined-treatment modulated apoptosis by increasing Bax/Bcl-2 ratio, and reduced Reactive Oxygen Species (ROS) production. We also observed that MET associated with TMZ was able to reduce the expression of glioma stem cells (GSC) marker CD90 particularly in T98G cells but not that of CD133. In vivo experiments showed that combined treatment with TMZ and MET significantly slowed down growth of TMZ-resistant tumors but did not affect overall survival of TMZ-sensitive tumor bearing mice. In conclusion, our results showed that metformin is able to enhance TMZ effect in TMZ-resistant cell line suggesting its potential use in TMZ refractory GBM patients. However, the lack of effect on a GBM malignancy marker like CD133 requires further evaluation since it might influence response duration.
Transcriptional control of early tract formation in the embryonic chick midbrain

The earliest step in establishing the complex neuronal networks in the vertebrate brain is the formation of a scaffold of axon tracts. How the formation of the early axon scaffold is controlled at the molecular level is unclear. Forming part of the scaffold, neurons located at the ventral midbrain-forebrain border (MFB) give rise to the medial longitudinal fascicle (mlf) and the posterior commissure (pc). We demonstrate that the homeobox genes Sax1, Six3, Emx2 and Pax6 are expressed in distinct domains in this area, suggesting that the specification of mlf and pc neurons might be controlled by the combinatorial activity of these transcription factors. We have tested this hypothesis by analysing the function of Sax1 in the embryonic chick brain. Gain-of-function experiments with Sax1 result in alterations to the early axon scaffold, most prominently an enlargement of the mlf at the expense of the pc. Ectopic expression of Sax1 also affects the expression of other ventral homeobox genes, particularly Six3 and Emx2. Our results indicate that the specification of neurons forming the early axon scaffold is governed by a homeobox code, thus resembling the mechanism of neuronal specification in the spinal cord.
Selective Inhibition of EZH2 by EPZ-6438 Leads to Potent Antitumor Activity in EZH2-Mutant Non-Hodgkin Lymphoma

Mutations within the catalytic domain of the histone methyltransferase EZH2 have been identified in subsets of patients with non-Hodgkin lymphoma (NHL). These genetic alterations are hypothesized to confer an oncogenic dependency on EZH2 enzymatic activity in these cancers. We have previously reported the discovery of EPZ005678 and EPZ-6438, potent and selective S-adenosyl-methionine-competitive small molecule inhibitors of EZH2. Although both compounds are similar with respect to their mechanism of action and selectivity, EPZ-6438 possesses superior potency and drug-like properties, including good oral bioavailability in animals. Here, we characterize the activity of EPZ-6438 in preclinical models of NHL. EPZ-6438 selectively inhibits intracellular lysine 27 of histone H3 (H3K27) methylation in a concentration- and time-dependent manner in both EZH2 wild-type and mutant lymphoma cells. Inhibition of H3K27 trimethylation (H3K27Me3) leads to selective cell killing of human lymphoma cell lines bearing EZH2 catalytic domain point mutations. Treatment of EZH2-mutant NHL xenograft-bearing mice with EPZ-6438 causes dose-dependent tumor growth inhibition, including complete and sustained tumor regressions with correlative diminution of H3K27Me3 levels in tumors and selected normal tissues. Mice dosed orally with EPZ-6438 for 28 days remained tumor free for up to 63 days after stopping compound treatment in two EZH2-mutant xenograft models. These data confirm the dependency of EZH2-mutant NHL on EZH2 activity and portend the utility of EPZ-6438 as a potential treatment for these genetically defined cancers. Mol Cancer Ther; 13(4); 842–54. ©2014 AACR.
Transcription Profiling of the Early Gravitropic Response in Arabidopsis Using High-Density Oligonucleotide Probe Microarrays1,212

Studies of plant tropisms, the directed growth toward or away from external stimuli such as light and gravity, began more than a century ago. Yet biochemical, physiological, and especially molecular mechanisms of plant tropic responses remain for the most part unclear. We examined expression of 8,300 genes during early stages of the gravitropic response using high-density oligonucleotide probe microarrays. Approximately 1.7% of the genes represented on the array exhibited significant expression changes within the first 30 min of gravity stimulation. Among gravity-induced genes were a number of genes previously implicated to be involved in gravitropism. However, a much larger number of the identified genes have not been previously associated with gravitropism. Because reorientation of plants may also expose plants to mechanical perturbations, we also compared the effects of a gentle mechanical perturbation on mRNA levels during the gravity response. It was found that approximately 39% of apparently gravity-regulated genes were also regulated by the mechanical perturbation caused by plant reorientation. Our study revealed the induction of complex gene expression patterns as a consequence of gravitropic reorientation and points to an interplay between the gravitropic and mechanical responses and to the extreme sensitivity of plants to even very gentle mechanical perturbations.
Powerful Women: Does Exposure Reduce Bias?

We exploit random assignment of gender quotas across Indian village councils to investigate whether having a female chief councillor affects public opinion towards female leaders. Villagers who have never been required to have a female leader prefer male leaders and perceive hypothetical female leaders as less effective than their male counterparts, when stated performance is identical. Exposure to a female leader does not alter villagers' taste preference for male leaders. However, it weakens stereotypes about gender roles in the public and domestic spheres and eliminates the negative bias in how female leaders' effectiveness is perceived among male villagers. Female villagers exhibit less prior bias, but are also less likely to know about or participate in local politics; as a result, their attitudes are largely unaffected. Consistent with our experimental findings, villagers rate their women leaders as less effective when exposed to them for the first, but not second, time. These changes in attitude are electorally meaningful: after 10 years of the quota policy, women are more likely to stand for and win free seats in villages that have been continuously required to have a female chief councillor.
Self-Efficacy as a Predictor of Dietary Change in a Low-Socioeconomic-Status Southern Adult Population

There is an increasing emphasis on designing health promotion interventions for low-socioeconomic-status (SES) individuals. However, many previously developed behavior change tools have not been tested in this population. Self-efficacy was measured at pre- and postintervention as part of a randomized clinical trial to reduce cholesterol levels in rural low-SES Southern adults. A 22-item scale was designed and validated to measure subjects' confidence in their abilities to make dietary changes. High mean self-efficacy was noted in both control and intervention subjects at pre- and postintervention. Mean self-efficacy score was a significant predictor of dietary change at both preintervention and postintervention. This study demonstrates that self-efficacy is a predictor of ability to make dietary changes in a low-SES rural population. This finding is of significance to researchers and practitioners wishing to design theory-based health promotion interventions in this population.
Effectiveness of antimicrobial adjuncts to scaling and root-planing therapy for periodontitis.

Periodontal diseases are bacterial infections that occur at or below the gum line. In contrast to gingivitis, which affects only the gums, periodontitis (severe periodontal disease) may involve the soft tissue and bone supporting the teeth. An estimated 70 percent of the adult U.S. population is affected by these infections. This includes 20–30 percent who have periodontitis that threatens the loss of teeth. Approximately $5 billion is spent on treatment of periodontal diseases each year. This report deals with the treatment of chronic periodontitis in adults. The key question is whether scaling and root planing (SRP) accompanied by an antimicrobial agent, as a supplemental or adjunct treatment, results in improved outcomes that persist over time in adults with chronic periodontitis when compared with SRP alone (or SRP and placebo). The primary outcomes of interest in this report are reductions in probing depth (PD) and gains in clinical attachment level (CAL). Of secondary interest are reductions in selected disease-causing bacteria, particularly reduction in the percentage of spirochetes present in dental plaque or in fluid from the gingival crevice.
Road scene perception based on fisheye camera, LIDAR and GPS data combination. (Perception de la route par combinaison des données caméra fisheye, Lidar et GPS)

Road scene understanding is one of key research topics of intelligent vehicles. This thesis focuses on detection and tracking of obstacles by multisensors data fusion and analysis. The considered system is composed of a lidar, a fisheye camera and aglobal positioning system (GPS). Several steps of the perception scheme are studied: extrinsic calibration between fisheye camera and lidar, road detection and obstacles detection and tracking. Firstly, a new method for extinsic calibration between fisheye camera and lidar is proposed. For intrinsic modeling of the fisheye camera, three models of the literatureare studied and compared. For extrinsic calibration between the two sensors, the normal to the lidar plane is firstly estimated based on the determination of n known z points. The extrinsic parameters are then computed using a least square approachbased on geometrical constraints, the lidar plane normal and the lidar measurements. The second part of this thesis is dedicated to road detection exploiting both fisheye camera and lidar data. The road is firstly coarse detected considering the illumination invariant image. Then the normalised histogram based classification is validated using the lidar data. The road segmentation is finally refined exploiting two successive roaddetection results and distance map computed in HSI color space. The third step focuses on obstacles detection, especially in case of motion blur. The proposed method combines previously detected road, map, GPS and lidar information.Regions of interest are extracted from previously road detection. Then road central lines are extracted from the image and matched with road shape model extracted from 2DŋSIG map. Lidar measurements are used to validated the results.The final step is object tracking still using fisheye camera and lidar. The proposed method is based on previously detected obstacles and a region growth approach. All the methods proposed in this thesis are tested, evaluated and compared to stateŋofŋtheŋart approaches using real data acquired with the IRTESŋSET laboratory experimental platform.
Emergence of Functional Specificity in Balanced Networks with Synaptic Plasticity

In rodent visual cortex, synaptic connections between orientation-selective neurons are unspecific at the time of eye opening, and become to some degree functionally specific only later during development. An explanation for this two-stage process was proposed in terms of Hebbian plasticity based on visual experience that would eventually enhance connections between neurons with similar response features. For this to work, however, two conditions must be satisfied: First, orientation selective neuronal responses must exist before specific recurrent synaptic connections can be established. Second, Hebbian learning must be compatible with the recurrent network dynamics contributing to orientation selectivity, and the resulting specific connectivity must remain stable for unspecific background activity. Previous studies have mainly focused on very simple models, where the receptive fields of neurons were essentially determined by feedforward mechanisms, and where the recurrent network was small, lacking the complex recurrent dynamics of large-scale networks of excitatory and inhibitory neurons. Here we studied the emergence of functionally specific connectivity in large-scale recurrent networks with synaptic plasticity. Our results show that balanced random networks, which already exhibit highly selective responses at eye opening, can develop feature-specific connectivity if appropriate rules of synaptic plasticity are invoked within and between excitatory and inhibitory populations. If these conditions are met, the initial orientation selectivity guides the process of Hebbian learning and, as a result, functionally specific and a surplus of bidirectional connections emerge. Our results thus demonstrate the cooperation of synaptic plasticity and recurrent dynamics in large-scale functional networks with realistic receptive fields, highlight the role of inhibition as a critical element in this process, and paves the road for further computational studies of sensory processing in neocortical network models equipped with synaptic plasticity.
Sampling within the genome for measuring within‐population diversity: trade‐offs between markers

Experimental results of diversity estimates in a set of populations often exhibit contradictory patterns when different marker systems are used. Using simulations we identified potential causes for these discrepancies. These investigations aimed also to detect whether different sampling strategies of markers within the genome resulted in different estimates of the diversity at the whole genome level. The simulations consisted in generating a set of populations undergoing various evolutionary scenarios which differed by population size, migration rate and heterogeneity of gene flow. Population diversity was then computed for the whole genome and for subsets of loci corresponding to different marker techniques. Rank correlation between the two measures of diversity were investigated under different scenarios. We showed that the heterogeneity of genetic diversity either between loci (genomic heterogeneity, GH) or among populations (population heterogeneity, PH) varied greatly according to the evolutionary scenario considered. Furthermore, GH and PH were major determinants of the level of rank correlation between estimates of genetic diversities obtained using different kinds of markers. We found a strong positive relationship between the level of the correlation and PH, whatever the marker system. It was also shown that, when GH values were constantly low during generations, a reduced number of microsatellites was enough to predict the diversity of the whole genome, whereas when GH increased, more loci were needed to predict the diversity and amplified fragment length polymorphism markers would be more recommended in this case. Finally the results are discussed to recommend strategies for gene diversity surveys.
Two-dimensional hexagonal tin: ab initio geometry, stability, electronic structure and functionalization

We study the structural, mechanical and electronic properties of the two-dimensional (2D) allotrope of tin: tinene/stanene using first-principles calculation within density functional theory, implemented in a set of computer codes. Continuing the trend of the group-IV 2D materials graphene, silicene and germanene; tinene is predicted to have a honeycomb lattice with lattice parameter of a0 = 4.62 Å and a buckling of d0 = 0.92 Å. The electronic dispersion shows a Dirac cone with zero gap at the Fermi energy and a Fermi velocity of v F = 0.97 × 10 6 ? > m s−1; including spin–orbit coupling yields a bandgap of 0.10 eV. The monolayer is thermally stable up to 700 K, as indicated by first-principles molecular dynamics, and has a phonon dispersion without imaginary frequencies. We explore applied electric field and applied strain as functionalization mechanisms. Combining these two mechanisms allows for an induced bandgap up to 0.21 eV, whilst retaining the linear dispersion, albeit with degraded electronic transport parameters.
Regionalization and the underuse of angiography in the Veterans Affairs Health Care System as compared with a fee-for-service system.

BACKGROUND Policies to concentrate or regionalize invasive procedures at high-volume medical centers are under active consideration. Such policies could improve outcomes among those who undergo procedures while increasing their underuse among those who never reach such centers. We compared the underuse of needed angiography after acute myocardial infarction in a traditional Medicare fee-for-service system with underuse in the regionalized Department of Veterans Affairs (VA) health care system. METHODS We studied 1665 veterans from 81 VA hospitals and 19,305 Medicare patients from 1530 non-VA hospitals, all of whom were elderly men. We compared adjusted angiography use and one-year mortality among patients for whom angiography was rated as clinically needed. We compared underuse in models before and after controlling for the on-site availability of cardiac procedures. RESULTS After adjustment for the need for angiography, underuse was present in both groups, but VA patients remained significantly less likely than Medicare patients to undergo angiography (43.9 percent vs. 51.0 percent; odds ratio, 0.75; 95 percent confidence interval, 0.57 to 0.96). After also controlling for on-site availability of cardiac procedures at the admitting hospital, we found no significant difference in the underuse of angiography among VA patients as compared with Medicare patients (odds ratio, 1.02; 95 percent confidence interval, 0.82 to 1.26) or in one-year mortality (odds ratio, 1.08; 95 percent confidence interval, 0.89 to 1.28). CONCLUSIONS There is underuse of needed angiography after acute myocardial infarction in both the VA and Medicare systems, but the rate of underuse is significantly higher in the VA. These differences appear to be associated with limited on-site availability of cardiac procedures in the regionalized VA health care system. Further work should focus on how regionalization policies could be improved with effective referral and triage processes.