Miracle-dz/UniFAR-FTUs huggingface dataset:
Stimulatory and Inhibitory Effects of Interleukin ( IL )-4 and ID 13 on the Production of Cytokines by Human Peripheral Blood Mononuclear Cells : Priming for ID 12 and Tumor Necrosis Factor c ~ Production

The production of cytokines in monocytes/macrophages is regulated by several different cytokines that have activating or inhibitory effects. Interleukin (IL)-10, IL-4, IL-13, and transforming growth factor (TGF)-~ are usually considered to be the most important macrophage-deactivating factors, with inhibitory effects on cytokine production. Unlike IL-IO and TGF-/3, which appear to act as downmodulators of many phagocytic cell functions, the mode of action of IL-4 and IL-13 is more complex. Addition of IL-4 and IL-13 to peripheral blood mononuclear cell (PBMC) cultures inhibited production of II. -12, tumor necrosis factor (TNF)-o~, IL-10, and II:1/~ induced by lipopolysaccharide (LPS) or Staphylococcus aureus added simultaneously with the cytokines. However, pretreatment of PBMC with II. -4 or I1. -13 for >--20 h enhanced the production of I1. -12 and TNF<~ in response to LPS or S. aureus several fold in these cells; this IL-4-induced priming for the two cytokines was inhibited by anti-IL-4 neutralizing antibodies. IL-4 priming also enhanced the accumulation of IL-12 and TNF-ot mR.NA induced by LPS and S. aureus. The enhanced accumulation of transcripts for the 1I. -12 p35 and p40 chains by IL-4 priming was reflected in enhanced secretion of both the IL-12 free p40 chain and the p70 heterodimer. These results suggest an unexpected complexity in the regulatory role of IL-4 and IL-13 in immune responses.
Pharmacokinetic-Pharmacodynamic Modeling of the In Vitro Activities of Oxazolidinone Antimicrobial Agents against Methicillin-Resistant Staphylococcus aureus

ABSTRACT Linezolid is the first FDA-approved oxazolidinone with activity against clinically important gram-positive pathogens, including methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). RWJ-416457 is a new oxazolidinone with an antimicrobial spectrum similar to that of linezolid. The goal of the present study was to develop a general pharmacokinetic (PK)-pharmacodynamic (PD) model that allows the characterization and comparison of the in vitro activities of oxazolidinones, determined in time-kill curve experiments, against MRSA. The in vitro activities of RWJ-416457 and the first-in-class representative, linezolid, against MRSA OC2878 were determined in static and dynamic time-kill curve experiments over a wide range of concentrations: 0.125 to 8 μg/ml (MIC, 0.5 μg/ml) and 0.25 to 16 μg/ml (MIC, 1 μg/ml), respectively. After correction for drug degradation during the time-kill curve experiments, a two-subpopulation model was simultaneously fitted to all data in the NONMEM VI program. The robustness of the model and the precision of the parameter estimates were evaluated by internal model validation by nonparametric bootstrap analysis. A two-subpopulation model, consisting of a self-replicating, oxazolidinone-susceptible and a persistent, oxazolidinone-insusceptible pool of bacteria was appropriate for the characterization of the time-kill curve data. The PK-PD model identified was capable of accounting for saturation in growth, delays in the onsets of growth and drug-induced killing, as well as naturally occurring bacterial death. The simultaneous fit of the proposed indirect-response, maximum-effect model to the data resulted in concentrations that produced a half-maximum killing effect that were significantly (P < 0.05) lower for RWJ-416457 (0.41 μg/ml) than for linezolid (1.39 μg/ml). In combination with the appropriate PK data, the susceptibility-based two-subpopulation model identified may provide valuable guidance for the selection of oxazolidinone doses or dose regimens for use in clinical studies.
Diagnosing smear-negative tuberculosis using case definitions and treatment response in HIV-infected adults.

OBJECTIVE To assess the diagnostic utility of expanded case definitions for HIV-associated smear-negative pulmonary tuberculosis (PTB) and extra-pulmonary TB (EPTB), and to derive objective criteria for response to anti-tuberculosis treatment. DESIGN A prospective cohort study of HIV-infected adults who met expanded clinical case definitions for smear-negative PTB and EPTB. METHODS All participants were started on rifampicin-based anti-tuberculosis treatment after mycobacterial cultures from multiple sites. At weeks 2, 4 and 8, response to treatment (RTT) was assessed by measuring changes in weight, haemoglobin, C-reactive protein, Karnofsky performance score and symptom count ratio. RESULTS Of 147 participants enrolled, 105 (71%) were diagnosed with definite (culture-positive) or probable (histological features) TB and 25 (17%) with possible TB (treatment response). The positive predictive value for the most common case definitions ranged from 89% to 96%. Significant improvements in all the RTT parameters occurred in the subjects with confirmed TB (P < 0.001). Clinically relevant RTT criteria were derived, two or more of which were met at week 8 in 97.5% of subjects with confirmed TB, 91.3% of subjects with possible TB and none of the subjects without TB. CONCLUSION Expanded case definitions could enhance the diagnosis of PTB and EPTB in HIV-infected adults in resource-limited settings. Using objective criteria, RTT can be assessed within 8 weeks of initiating anti-tuberculosis treatment.
Instantons and Large N: An Introduction to Non-Perturbative Methods in Quantum Field Theory

This highly pedagogical textbook for graduate students in particle, theoretical and mathematical physics, explores advanced topics of quantum field theory. Clearly divided into two parts; the first focuses on instantons with a detailed exposition of instantons in quantum mechanics, supersymmetric quantum mechanics, the large order behavior of perturbation theory, and Yang–Mills theories, before moving on to examine the large N expansion in quantum field theory. The organised presentation style, in addition to detailed mathematical derivations, worked examples and applications throughout, enables students to gain practical experience with the tools necessary to start research. The author includes recent developments on the large order behavior of perturbation theory and on large N instantons, and updates existing treatments of classic topics, to ensure that this is a practical and contemporary guide for students developing their understanding of the intricacies of quantum field theory.
Explaining alcohol use and suicide risk: a moderated mediation model involving insomnia symptoms and gender.

STUDY OBJECTIVES The purpose of the study was to examine whether insomnia symptoms and nightmares mediated the relation between alcohol use and suicide risk. Further, we examined whether this mediation was moderated by gender. DESIGN The study consisted of questionnaires administered online examining insomnia symptoms, nightmares, alcohol use, and suicide risk. SETTING University. PATIENTS OR PARTICIPANTS 375 undergraduate students at a large, public university in the southeastern United States. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Results indicated that insomnia symptoms significantly mediated the relation between alcohol use and suicide risk; however, this mediation was moderated by gender. For women, there was both a direct effect of alcohol use on suicide risk as well as an indirect effect of alcohol use through insomnia symptoms increasing suicide risk. For men, there was no direct effect of alcohol use on suicide risk, but there was a significant indirect effect of alcohol use increasing suicide risk through insomnia symptoms. Nightmares were not related to alcohol use, and the association between nightmares and suicide risk was found to be independent of alcohol use. CONCLUSIONS Insomnia symptoms are an important factor in explaining the mechanism by which alcohol use increases suicide risk.
The Lymphotoxin Pathway Regulates Aire-Independent Expression of Ectopic Genes and Chemokines in Thymic Stromal Cells1

Medullary thymic epithelial cells (mTEC) play an important and unique role in central tolerance, expressing tissue-restricted Ags (TRA) which delete thymocytes autoreactive to peripheral organs. Since deficiencies in this cell type or activity can lead to devastating autoimmune diseases, it is important to understand the factors which regulate mTEC differentiation and function. Lymphotoxin (LT) ligands and the LTβR have been recently shown to be important regulators of mTEC biology; however, the precise role of this pathway in the thymus is not clear. In this study, we have investigated the impact of this signaling pathway in greater detail, focusing not only on mTEC but also on other thymic stromal cell subsets. LTβR expression was found in all TEC subsets, but the highest levels were detected in MTS-15+ thymic fibroblasts. Rather than directing the expression of the autoimmune regulator Aire in mTEC, we found LTβR signals were important for TRA expression in a distinct population of mTEC characterized by low levels of MHC class II (mTEClow), as well as maintenance of MTS-15+ fibroblasts. In addition, thymic stromal cell subsets from LT-deficient mice exhibit defects in chemokine production similar to that found in peripheral lymphoid organs of Lta−/− and Ltbr−/− mice. Thus, we propose a broader role for LTα1β2-LTβR signaling in the maintenance of the thymic microenvironments, specifically by regulating TRA and chemokine expression in mTEClow for efficient induction of central tolerance.
Social modernization and the increase in the divorce rate.

The author develops a micro-model of marital interactions that is used to analyze factors affecting the divorce rate in modern industrialized societies. The core of the model is the concept of production of marital gain and mutual control of this production. "The increase of divorce rates, then, is explained by a steady decrease of institutional and social embeddedness, which helps to solve this kind of an 'assurance game. ' The shape of the individual risk is explained by the typical form of change of the 'production functions' of marriages within the first period of adaptation. The inconsistent results concerning womens' labor market participation in linear regression models are explained as a consequence of the (theoretical and statistical) 'interaction' of decreases in embeddedness and increases in external alternatives for women. " Comments are included by Karl-Dieter Opp (pp. 278-82) and Ulrich Witt (pp. 283-5).
Forschungsberichte der Fakultät IV – Elektrotechnik und Informatik Revisiting Content Availability in Distributed Online Social Networks

Online Social Networks (OSN) are among the most popular applications in today’s Internet. Decentralized online social networks (DOSNs), a special class of OSNs, promise better privacy and autonomy than traditional centralized OSNs. However, ensuring availability of content when the contentowner is not online remains a major challenge. In this paper, we rely on the structure of the social graphs underlying DOSN for replication. In particular, we propose that friends, who are anyhow interested in the content, are used t o replicate the users content. We study the availability of su ch natural replication schemes via both theoretical analysisas well as simulations based on data from OSN users. We find that the availability of the content increases drastically when compared to the online time of the user, e. g. , by a factor of more than 2 f or 90% of the users. Thus, with these simple schemes we provide a baseline for any more complicated content replication sche me.
Evaluation of predictors of weaning from mechanical ventilation in pediatric patients

Objective criteria for ending mechanical ventilation have not been established for infants and children. A recent study in adult patients developed two new indexes, the Rapid Shallow Breathing Index (RSB) and the CROP Index for predicting success or failure of extubation. We decided to evaluate the applicability of these indices to intubated, mechanically ventilated pediatric patients. For this evaluation the indices were adapted to the physiology of infants and children. A pneumotachograph was used to measure spontaneous tidal volume, respiratory rate and dynamic compliance. The tidal volume and the dynamic compliance were corrected for the patient's body weight. Based on the data collected a cutoff value for each index was determined. Of 47 sets of patient data, 38 (81%) were collected during successful extubations, 9 (19%) during failed extubations.
Exploring information system evaluation in Indian manufacturing sector

The present paper is an attempt to explore the IS evaluation in Indian manufacturing sector. It aims to find out the major dimensions for the evaluation of IS by the users and organisations. The results of the study are based on the primary data collected from 840 users taken from 70 large and medium manufacturing organisations using survey method. The results indicate that negligible IS evaluation was undertaken at the organisation level and the evaluation methodologies were technical in nature. Seven factors from user-based IS evaluation were deducted using factor analysis. No significant variation was found across these factors across different functional areas while significant differences were observed across different levels of management. The findings of the study carry value for the IS managers and vendors dealing with Indian manufacturing sector and provide a glimpse of the state of IS evaluation in India. The present study is an attempt to explore the IS evaluation in India, a relatively unexplored field till date, hence, provides valuable insights regarding the status of IS evaluation in Indian manufacturing sector. It will help in filling the existing IS research gaps in the context of India, an emerging market for IS/IT applications.
Many faces of dogmatism: Prejudice as a way of protecting certainty against value violators among dogmatic believers and atheists

In this article, we suggest that dogmatic beliefs, manifested as strong beliefs that there is no God (i.e., dogmatic atheism) as well as strong beliefs in God (i.e., religious orthodoxy), can serve as a cognitive response to uncertainty. Moreover, we claim that people who dogmatically do not believe in religion and those who dogmatically believe in religion are equally prone to intolerance and prejudice towards groups that violate their important values. That is because prejudice towards these groups may be an efficient strategy to protect the certainty that strong beliefs provide. We tested these assumptions in two studies. In Study 1 and Study 2, we demonstrated that dogmatic beliefs mediate the relationship between intolerance to uncertainty and both, religious orthodoxy and dogmatic atheism. In addition, in Study 2 we showed that both the religiously orthodox and dogmatic atheists become prejudiced towards groups that violate their values and that these effects are especially strong under experimentally induced uncertainty. In this study, we focused on atheists and homosexuals as groups that pose a threat to Christian's religious worldviews, and Catholics and pro-life supporters as groups that pose a threat to the values of atheists. The results are discussed in relation to past research on dogmatism and religion, as well as with reference to what this means for the study of prejudice.
Incremental effects of reward on experienced performance pressure: positive outcomes for intrinsic interest and creativity

Two field studies and a laboratory study examined the influence of reward for high performance on experienced performance pressure, intrinsic interest and creativity. Study 1 found that employees' expected reward for high performance was positively related to performance pressure which, in turn, was positively associated with the employees' interest in their jobs. Study 2 replicated this finding and showed that intrinsic interest, produced by performance pressure, was positively related to supervisors' ratings of creative performance. Study 3 found that college students' receipt of reward for high performance increased their experienced performance pressure which, in turn, was positively related to intrinsic interest and creativity. Copyright © 2008 John Wiley & Sons, Ltd.
INTERVARIETAL DIFFERENCES IN NITROGEN CONTENT AND NITRATE ASSIMILATION IN WHEAT (TRITICUM AESTIVUM L.) UNDER SALT STRESS

Effect of five NaCl salinity treatments (0, 50, 100, 200 and 300 mM) given at different growth and developmental stages on total N level and in vitro nitrate reductase activity (NRA) in leaves and roots of two wheat cultivars viz., Ghods and Boolani was studied in greenhouse conditions. In response to salinity treatments, total N concentrations and NO3 - assimilation rates in Ghods, a saltsensitive cultivar, were suppressed more than that of Boolani, a salt-resistant cultivar. However, not much differences in root N content were found between the cultivars. Our data suggest that NRA is affected under the influence of salt stress more than that of N concentration. In addition, there was no clear correlation between N levels and the activity of NR, particularly in leaves. The effect of salinity stress on N content and NRA depends on the cultivar, organ, developmental stage and degree of salt stress.
Assisted Reproductive Technology and Birth Defects Among Liveborn Infants in Florida, Massachusetts, and Michigan, 2000-2010.

IMPORTANCE Use of assisted reproductive technology (ART) has been associated with increased risks for birth defects. Variations in birth defect risks according to type of ART procedure have been noted, but findings are inconsistent. OBJECTIVES To examine the prevalence of birth defects among liveborn infants conceived with and without ART and to evaluate risks associated with certain ART procedures among ART-conceived infants. DESIGN, SETTING, AND PARTICIPANTS Used linked ART surveillance, birth certificates, and birth defects registry data for 3 states (Florida, Massachusetts, and Michigan). Methods for ascertaining birth defect cases varied by state. Resident live births during 2000 to 2010 were included, and the analysis was conducted between Feburary 2015 and August 2015. EXPOSURES Use of ART among all live births and use of certain ART procedures among ART births. MAIN OUTCOME AND MEASURES Prevalence of selected chromosomal and nonchromosomal birth defects that are usually diagnosed at or immediately after birth. RESULTS Of the 4 618 076 liveborn infants between 2000 and 2010, 64 861 (1.4%) were conceived using ART. Overall, the prevalence of 1 or more of the selected nonchromosomal defects was 58.59 per 10 000 for ART infants (n = 389) vs 47.50 per 10 000 for non-ART infants (n = 22 036). The association remained significant after adjusting for maternal characteristics and year of birth (adjusted risk ratio [aRR], 1.28; 95% CI, 1.15-1.42). Similar differences were observed for singleton ART births vs their non-ART counterparts (63.69 per 10 000 [n = 218] vs 47.17 per 10 000 [n = 21 251]; aRR, 1.38; 95% CI, 1.21-1.59). Among multiple births, the prevalence of rectal and large intestinal atresia/stenosis was higher for ART births compared with non-ART births (aRR, 2.39; 95% CI, 1.38-4.12). Among ART births conceived after fresh embryo transfer, infants born to mothers with ovulation disorders had a higher prevalence of nonchromosomal birth defects (aRR, 1.53; 95% CI, 1.13-2.06) than those born to mothers without the diagnosis, and use of assisted hatching was associated with birth defects among singleton births (aRR, 1.55; 95% CI, 1.10-2.19). Multiplicity-adjusted P values for these associations were greater than . 05. CONCLUSIONS AND RELEVANCE Infants conceived after ART had a higher prevalence of certain birth defects. Assisted hatching and diagnosis of ovulation disorder were marginally associated with increased risks for nonchromosomal birth defects; however, these associations may be caused by other underlying factors.
Comprehensive Understanding of Coulomb Scattering Mobility in Biaxially Strained-Si pMOSFETs

In this brief, the effect of biaxial tensile strain on the hole mobility limited by substrate-impurity and interface-state Coulomb scatterings (mu<sub>sub</sub> and mu<sub>it</sub>, respectively) in an inversion layer of (100)/lang110 rang pMOSFETs is investigated experimentally with strained-Si (s-Si) channels on relaxed Si<sub>1-</sub> <i>x</i>Ge<i>x</i> (<i>x</i> = 0.1-0.4) substrates. Our results show that biaxial tensile strain degrades the hole mobility limited by substrate-impurity Coulomb scattering (mu<sub>sub</sub>) , while it enhances the hole mobility limited by interface-state Coulomb scattering (mu<sub>it</sub>) because of the increase in the average distance between holes and scattering centers at the Si/SiO<sub>2</sub> interface after the tensile strain. These trends are opposite to that of electron ones. The different strain dependence between electrons and holes in terms of mu<sub>sub</sub> and mu<sub>it</sub> can be explained by a universal two-band model based on the subband structures of electrons and holes.
Imaging molecular dynamics in vivo – from cell biology to animal models

Advances in fluorescence microscopy have enabled the study of membrane diffusion, cell adhesion and signal transduction at the molecular level in living cells grown in culture. By contrast, imaging in living organisms has primarily been restricted to the localization and dynamics of cells in tissues. Now, imaging of molecular dynamics is on the cusp of progressing from cell culture to living tissue. This transition has been driven by the understanding that the microenvironment critically determines many developmental and pathological processes. Here, we review recent progress in fluorescent protein imaging in vivo by drawing primarily on cancer-related studies in mice. We emphasize the need for techniques that can be easily combined with genetic models and complement fluorescent protein imaging by providing contextual information about the cellular environment. In this Commentary we will consider differences between in vitro and in vivo experimental design and argue for an approach to in vivo imaging that is built upon the use of intermediate systems, such as 3-D and explant culture models, which offer flexibility and control that is not always available in vivo. Collectively, these methods present a paradigm shift towards the molecular-level investigation of disease and therapy in animal models of disease.