Miracle-dz/UniFAR-FTUs huggingface dataset:
Desensitization in vitro: the role of T-suppressor cells, T-suppressor factor and T-acceptor cells in the inhibition of the passive transfer of contact sensitivity to picryl chloride by exposure to antigen in vitro.

This paper investigates desensitization in vitro, e.g. the inhibition of the transfer of contact sensitivity to picryl chloride by incubation of the passive transfer population with picrylated spleen cells. It asks whether desensitization is based on the same T-suppressor circuit which is responsible for the inhibition of passive transfer by antigen-specific T-suppressor factor (TsF). In this circuit, the T-suppressor cell which acts at the efferent stage (Ts-eff) makes TsF. This TsF depresses contact sensitivity indirectly by arming a T-acceptor cell (Tacc). The armed Tacc, when exposed to antigen (picrylated spleen cells), liberates a non-specific inhibitor which blocks the transfer of contact sensitivity. The three elements of this T-suppressor circuit occur in nylon wool-purified T cells prepared from the lymph nodes and spleens of mice four days after immunization with picryl chloride. This population transfers contact sensitivity and can be desensitized in vitro. It contains Ts-eff which can be isolated by panning (adherence) on picrylated albumin and detected by their ability to inhibit passive transfer. The 24 hr supernatant of cultures of these cells contains TsF. Finally the population contains Tacc which appear in the spleen 2 days after immunization and virtually disappear by 10 days. Further experiments demonstrated that the Ts-eff and the Tacc were not merely present but actually required for desensitization in vitro. Immune cells depleted of both Ts-eff (by panning on picrylated albumin) and Tacc (by arming with anti-oxazolone TsF and panning on oxazolonated albumin) cannot be desensitized. To restore desensitization both Ts-eff and Tacc must be added back. The Ts-eff were characterized as cyclophosphamide resistant, adult thymectomy sensitive cells (Cyr, ATxs), which adhered to antigen and were produced only by specific immunization. The Tacc were characterized as Cys, ATxs cells which adhered to antigen only after arming with antigen-specific T-suppressor factor and were produced after immunization with an unrelated contact sensitizer, `oxazolone'. It was concluded that desensitization in vitro was due to the interaction of two distinct T cells: the T-suppressor cell which acts at the efferent stage of the contact sensitivity reaction and the T-acceptor cell which becomes armed with the specific T-suppressor factor produced by the Ts-eff.
Identification and Expression Analyses of Putative Sesquiterpene Synthase Genes in Phormidium sp. and Prevalence of geoA-Like Genes in a Drinking Water Reservoir

ABSTRACT The occurrence of taste and odor problems in drinking water supplies is a widespread phenomenon. From a Saxonian water reservoir we isolated a cyanobacterial species which was classified as Phormidium sp. Under laboratory conditions it produced an earthy-musty smell due to the synthesis of geosmin. The only genes shown to be involved in geosmin biosynthesis are cyc2 and geoA of Streptomyces. Based on the alignment of Cyc2 with a putative sesquiterpene synthase of Nostoc punctiforme, a degenerate primer pair was designed. By PCR, we could amplify two similar genes in Phormidium sp. , which we named geoA1 and geoA2. Their expression was studied by reverse transcription-PCR. This revealed that both genes are expressed at 20°C and a light-dark cycle of 12 h. Expression was not detectable at the end of a 24-h dark period. To analyze the prevalence of geoA1 and geoA2 in samples from the phytobenthos, we generated PCR fragments with the same degenerate primer pair. Fifty-five different sequences that might represent geoA variants were obtained. The GC content ranged from 42% to 67%, suggesting that taxonomically very different bacteria might contain such genes.
Accelerated infant weight gain and risk for nonalcoholic fatty liver disease in early adulthood.

INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic metabolic syndrome. Some studies demonstrated an association between small size at birth and NAFLD. Rapid catch-up in weight often follows small birth size and has been associated with metabolic syndrome, but its association with NAFLD remained unknown. PATIENTS AND METHODS In 268 adults aged 18-24 years, body mass index, waist circumference, triglyceride, γ-glutamyltransferase, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase levels were determined. Fatty liver index (FLI; 0-100) was calculated. Associations of birth weight SD score and first year gain in weight and length SD scores were determined with FLI and other liver markers. Comparisons were performed between subjects with and without rapid catch-up in weight in the first year of life. Furthermore, a FLI score (low, intermediate, high risk for NAFLD) was assigned to each participant to determine clinical relevance, and ordinal regression analyses were performed. RESULTS Gain in weight in the first 3 months of life was associated with FLI as a continuous variable, whereas low birth weight was not. There were no significant associations with γ-glutamyltransferase, alanine aminotransferase, or aspartate aminotransferase. Of the subjects with rapid catch-up in weight for length, 27.8% had an intermediate or high FLI at the age of 21 years, compared with 5.3% of subjects with slow catch-up. Rapid catch-up was also associated with a higher FLI score after adjustments (odds ratio, 11.7; P = .016). CONCLUSION Accelerated gain in weight for length in the first 3 months of life is associated with a higher risk for NAFLD in early adulthood, whereas small size at birth is not.
Coupling Between Neuronal Firing, Field Potentials, and fMRI in Human Auditory Cortex

Functional magnetic resonance imaging (fMRI) is an important tool for investigating human brain function, but the relationship between the hemodynamically based fMRI signals in the human brain and the underlying neuronal activity is unclear. We recorded single unit activity and local field potentials in auditory cortex of two neurosurgical patients and compared them with the fMRI signals of 11 healthy subjects during presentation of an identical movie segment. The predicted fMRI signals derived from single units and the measured fMRI signals from auditory cortex showed a highly significant correlation (r = 0.75, P < 10–47). Thus, fMRI signals can provide a reliable measure of the firing rate of human cortical neurons.
Efficacy of albuterol in the management of bronchiolitis.

I read with interest the article by Gadomski et al entitled Efficacy of Albuterol in the Management of Bronchiolitis.1 It is a thoughtful study regarding an important question with careful attention to the inclusion and exclusion criteria. However, I have the following three concerns. First of all, I am curious as to why the authors chose to measure outcomes at 30 and 60 minutes. The peak impact of nebulized albuterol is 1 to 2 hours after treatment while that of oral albuterol is 2 to 3 hours after the dose.
Barrier Formation

Enamel fluorosis is an irreversible structural enamel defect following exposure to supraoptimal levels of fluoride during amelogenesis. We hypothesized that fluorosis is associated with excess release of protons during formation of hypermineralized lines in the mineralizing enamel matrix. We tested this concept by analyzing fluorotic enamel defects in wild-type mice and mice deficient in anion exchanger-2a,b (Ae2a,b), a transmembrane protein in maturation ameloblasts that exchanges extracellular Cl− for bicarbonate. Defects were more pronounced in fluorotic Ae2a,b−/− mice than in fluorotic heterozygous or wild-type mice. Phenotypes included a hypermineralized surface, extensive subsurface hypomineralization, and multiple hypermineralized lines in deeper enamel. Mineral content decreased in all fluoride-exposed and Ae2a,b−/− mice and was strongly correlated with Cl−. Exposure of enamel surfaces underlying maturation-stage ameloblasts to pH indicator dyes suggested the presence of diffusion barriers in fluorotic enamel. These results support the concept that fluoride stimulates hypermineralization at the mineralization front. This causes increased release of protons, which ameloblasts respond to by secreting more bicarbonates at the expense of Cl− levels in enamel. The fluoride-induced hypermineralized lines may form barriers that impede diffusion of proteins and mineral ions into the subsurface layers, thereby delaying biomineralization and causing retention of enamel matrix proteins.
The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins

Nuclear import and export of viral nucleic acids is crucial for the replication cycle of many viruses, and elucidation of the mechanism of these steps may provide a paradigm for understanding general biological processes. Influenza virus replicates its RNA genome in the nucleus of infected cells. The influenza virus NS2 protein, which had no previously assigned function, was shown to mediate the nuclear export of virion RNAs by acting as an adaptor between viral ribonucleoprotein complexes and the nuclear export machinery of the cell. A functional domain on the NS2 with characteristics of a nuclear export signal was mapped: it interacts with cellular nucleoporins, can functionally replace the effector domain of the human immunodeficiency virus type 1 (HIV‐1) Rev protein and mediates rapid nuclear export when cross‐linked to a reporter protein. Microinjection of anti‐NS2 antibodies into infected cells inhibited nuclear export of viral ribonucleoproteins, suggesting that the Rev‐like NS2 mediates this process. Therefore, we have renamed this Rev‐like factor the influenza virus nuclear export protein or NEP. We propose a model by which NEP acts as a protein adaptor molecule bridging viral ribonucleoproteins and the nuclear pore complex.
Causal Modeling, Discovery, & Inference for Software Engineering

Empirical studies in software engineering frequently rely on correlation data in an effort to demonstrate that a process or tool affects an important or meaningful outcome, with the ultimate goal of improving software engineering practice. But all students of statistics know that "correlation does not imply causation," and so causal conclusions (using traditional methods) from observational studies are inevitably highly constrained. These studies thus have limited impact on real world practice. In this paper, we use methods beyond mere correlation, and apply techniques of causal discovery to software engineering data as a means of unambiguously determining cause and effect. We apply causal discovery techniques to a set of observational data on open source projects, use the results to determine some consequences of architectural flaws, and show how causal inference may be applied to software engineering data in the future.
Effect of an acute glucose overload on Islet cell morphology and secretory function in the toad.

The aim of this work was to study the effect of induced hyperglycemia on islet cell mass and insulin secretion in normal toads. Immunolabeled beta cell area, replication (bromodeoxyuridine) and apoptosis (propidium iodide) rate, islet neogenesis (cytokeratin), and insulin secretion in vitro were measured in adult male specimens of Bufo arenarum during and after interruption of the injection of either a 50% glucose solution (2 g/100 g) or its vehicle for 4 days. Glucose administration caused hyperglycemia (122.6 +/- 16.7 and 508.3 +/- 115.9 mg/dl vs 23.5 +/- 1.26 and 22.8 +/- 1.8 mg/dl, at days 3 and 5, respectively, P < 0.05) and a significant decrease in the number of islets/mm(2) (day 3: 9.7 +/- 0.9 vs 3.3 +/- 0.4, P < 0.05; day 5: 9.4 +/- 0.8 vs 7.4 +/- 0.6; day 9: 9.6 +/- 0.9 vs 6.2 +/- 0.4, P < 0.05) and in the percentage of immunolabeled beta cell area (day 3: 2.07 +/- 0.2 vs 0.5 +/- 0.1%, P < 0.05; day 5: 1.8 +/- 0.1 vs 0.6 +/- 0.1%; day 9: 1.7 +/- 0.1 vs 0.7 +/- 0.1%, P < 0.05). Glucose-injected animals had a simultaneous significantly higher percentage of BrdU-labeled beta cells (day 3: 0.46 +/- 0.02 vs 0.23 +/- 0.03%; day 5: 0.54 +/- 0.13 vs 0.22 +/- 0.02%; day 9: 0.61 +/- 0.0 vs 0.27 +/- 0.05%, P < 0.05) and cytokeratin-labeled endocrine cells (day 3: 0.21 +/- 0.06 vs 0.01 +/- 0.00%; day 5: 0.17 +/- 0.06 vs 0.01 +/- 0.01%; day 9: 1.25 +/- 0.2 vs 0.01 +/- 0.008%, P < 0.05) and a higher rate of apoptotic beta cells (day 3: 0.14 +/- 0.04 vs 0.05 +/- 0.02%; day 5: 0.4 +/- 0.06 vs 0.05 +/- 0.2, P < 0.05; day 9: 0.47 +/- 0.04 vs 0.06 +/- 0.03, P < 0.05). Comparable amounts of insulin were secreted in vitro by both groups in response to 2 mM glucose, whereas there was a significantly reduced response to 8 mM glucose in treated animals (day 3: 73 +/- 12 vs 165 +/- 20%; day 5: 74 +/- 11 vs 204 +/- 18%, P < 0.05). This decreased response to high glucose reverted to normal after removal of the glucose injection. These results show for the first time that short-term hyperglycemia triggers marked morphological and transient secretory changes in the toad pancreas similar in part to those elicited in the pancreas of several mammals. As with other results previously reported, these results support the usefulness of the toad as an alternative easily handled model to study the growth and secretory function of the endocrine pancreas.
Ligand-dependent Formation of Retinoid Receptors, Receptor-interacting Protein 140 (RIP140), and Histone Deacetylase Complex Is Mediated by a Novel Receptor-interacting Motif of RIP140*

Receptor-interacting protein 140 (RIP140) interacts with retinoic acid receptor and retinoid X receptor in a ligand-dependent manner and suppresses retinoic acid (RA) induction of its target genes. The receptor-interacting motif is mapped to a C-terminal peptide sequence (LTKTNPILYYMLQK) of RIP140. The functional role of this motif in mediating the suppressive effects of RIP140 on RA induction is demonstrated in mutation studies. RA induces coimmunoprecipitation of histone deacetylase 3 with retinoic acid receptor/retinoid X receptor in the presence of wild type RIP140, but not in the presence of the C-terminal motif-deleted RIP140. A decrease in histone acetylation on the promoter region that carries a RA response element is associated with the expression of wild type RIP140, but not with expression of the mutant RIP140, in a dose-dependent manner. These data provide a molecular explanation for RIP140 acting as a novel ligand-dependent, negative modulator of RA-regulated gene expression.
Body Mass Index Is an Important Predictor for Suicide: Results from a Systematic Review and Meta-Analysis.

Public health concerns for the independent management of obesity and suicidal behavior are rising. Emerging evidence suggests body weight plays an important role in quantifying the risk of suicide. In light of these findings, we aimed to clarify the association between body mass index (BMI) and suicidal behavior by systematically reviewing and evaluating the literature. Studies were identified by searching MEDLINE, EMBASE, PsycINFO, and CINAHL from inception to January 2015, supplemented by hand and grey literature searches. Study screening, data extraction, and risk of bias assessment were conducted in duplicate. We included 38 observational studies. Meta-analyses supported an inverse association between BMI and completed suicide. Pooled summary estimates demonstrated that underweight was significantly associated with an increased risk of completed suicide (HR = 1.21, 95% CI 1.07 to 1.36, p = .002), and obesity (HR = 0.71, 95% CI 0.56 to 0.89, p = .003) and overweight (HR = 0.78, 95% CI 0.75 to 0.82, p < .0001) were significantly associated with a decreased risk of completed suicide relative to normal weight. A qualitative summary of the literature demonstrated conflicting evidence regarding the association between BMI and attempted suicide and revealed no association between BMI and suicidal ideation. BMI may be used to aid the assessment of suicide risk, especially that of completed suicide. However, unmeasured confounders and systematic biases of individual studies limit the quality of evidence.
Predictive crystallization of ribonuclease A via rapid screening of osmotic second virial coefficients

Important progress has been made in recent years toward developing a molecular‐level understanding of protein phase behavior in terms of the osmotic second virial coefficient, a thermodynamic parameter that characterizes pairwise protein interactions. Yet there has been little practical application of this knowledge to the field of protein crystallization, largely because of the difficult and time‐consuming nature of traditional techniques for characterizing protein interactions. Self‐interaction chromatography has recently been proposed as a highly efficient method for measuring the osmotic second virial coefficient. The utility of the technique is examined in this work by characterizing virial coefficients for ribonuclease A under 59 solution conditions using several crystallization additives, including PEG, sodium chloride, ammonium sulfate, and propanol. The virial coefficient measurements show some counterintuitive trends and shed light on the previous difficulties in crystallizing ribonuclease A. Crystallization experiments at the corresponding solution conditions were conducted by using ultracentrifugal crystallization. Using this methodology, ribonuclease A crystals were obtained under conditions for which the virial coefficients fell within the “crystallization slot. ” Crystallographic characterization showed that the crystals diffract to high resolution. Metastable crystals were also obtained for conditions outside, but near, the “crystallization slot,” and they could also be frozen and used to collect structural information. Proteins 2003;50:303–311. © 2002 Wiley‐Liss, Inc.
Paracrine factors of human mesenchymal stem cells increase wound closure and reduce reactive oxygen species production in a traumatic brain injury in vitro model

Traumatic brain injury (TBI) consists of a primary and a secondary insult characterized by a biochemical cascade that plays a crucial role in cell death in the brain. Despite the major improvements in the acute care of head injury victims, no effective strategies exist for preventing the secondary injury cascade. This lack of success might be due to that most treatments are aimed at targeting neuronal population, even if studies show that astrocytes play a key role after a brain damage. In this work, we propose a new model of in vitro traumatic brain-like injury and use paracrine factors released by human mesenchymal stem cells (hMSCs) as a neuroprotective strategy. Our results demonstrate that hMSC-conditioned medium increased wound closure and proliferation at 12 h and reduced superoxide production to control conditions. This was accompanied by changes in cell morphology and polarity index, as both parameters reflect the ability of cells to migrate toward the wound. These findings indicate that hMSC is an important regulator of oxidative stress production, enhances cells migration, and shall be considered as a useful neuroprotective approach for brain recovery following injury.
A simple method for automated equilibration detection in molecular simulations

Molecular simulations intended to compute equilibriumproperties are o en initiated fromconfigurations that are highly atypical of equilibrium samples, a practice which can generate a distinct initial transient in mechanical observables computed from the simulation trajectory. Traditional practice in simulation data analysis recommends this initial portion be discarded to equilibration, but no simple, general, and automated procedure for this process exists. Here, we suggest a conceptually simple automated procedure that does not make strict assumptions about the distribution of the observable of interest, in which the equilibration time is chosen to maximize the number of e ectively uncorrelated samples in the production timespan used to compute equilibrium averages. We present a simple Python reference implementation of this procedure, and demonstrate its utility on typical molecular simulation data.
Seed dispersal and predation by Yakushima macaques, Macaca fuscata yakui, in a warm temperate forest of Yakushima Island, southern Japan

The relationships between fruit morphology and the foraging behavior of the Yakushima macaque, Macaca fuscata yakui were studied during a 9-month field study and series of laboratory experiments on Yakushima Island, southern Japan. These relationships may affect seed germination traits through seed dispersal. The macaques’ foraging behavior was observed in order to obtain data concerning the treatment of pulp and seeds. Seeds in feces and spat seeds were collected and analyzed. A linear discriminant analysis of the data led to the following results: (i) an increase in the relative flesh volume of a fruit was one of the potential factors which increased the probability of seed dispersal by the macaques; and (ii) seed size was an important parameter in relation to the type of seed dispersal (by defecation or spitting out). The germination test was conducted in a laboratory, then the germination rates and delays of dispersed seeds were compared with those of seeds collected directly from trees. The germination of dispersed seeds of Ficus thunbergii, Eurya japonica, and Vaccinium bracteatum, was significantly enhanced by passage through the macaques’ gut. The enhanced germination behavior was not seen in larger seeds, such as those of Psychotria serpens, Myrsine seguinii, Diospyros morrisiana, and Neolitsea sericea. The germination enhancement in small-seeded plants could be due to a sorting effect from the passage through the gut, which selects seeds with a narrower range of germination traits.
Predicting Hepatitis C Virus Protease Cleavage Sites Using Generalized Linear Indicator Regression Models

This paper discusses how to predict hepatitis C virus protease cleavage sites in proteins using generalized linear indicator regression models. The mutual information is used for model-size optimization. Two simulation strategies are adopted, i.e., building a model based on published peptides and building a model based on the published peptides plus newly collected sequences. It is found that the latter outperforms the former significantly. The simulation also shows that the generalized linear indicator regression model far outperforms the multilayer perceptron model
Prospects for atherosclerosis regression through increase in high-density lipoprotein and other emerging therapeutic targets

In a process often seen as progressive and irreversible, deposition and retention of lipoproteins and the consequent inflammatory reaction result in the accumulation of atherosclerotic plaques from an early age. However, striking effects observed in experimental models support the concept that atherosclerosis can regress. This is often accompanied by changes in plaque composition favouring stability and decreased likelihood of rupture. Large clinical trials have established the value of low-density lipoprotein cholesterol reduction with statin treatment, although this may prevent no more than 30% of all cardiovascular events, and the magnitude of effect on plaque regression seems relatively modest. High-density lipoprotein cholesterol (HDL-C) is well recognised as an important and independent protective factor, although treatment options to increase HDL-C have until now been limited. The recent emergence of new treatments will probably establish increased HDL-C as another important strategy in antiatherosclerosis treatment. Beyond HDL-C increases, further appreciation of mechanisms of cellular lipid homoeostasis and regulation of gene transcription have revealed new targets for atherosclerosis treatment. This review considers emerging approaches to plaque regression together with some of the parallel developments in imaging technology that will improve our appreciation of response to treatment.