Miracle-dz/UniFAR-FTUs huggingface dataset:
Resolution of allergic airway inflammation and airway hyperreactivity is mediated by IL-17-producing {gamma}{delta}T cells.

RATIONALE gammadeltaT lymphocytes are enriched within the epithelial microenvironment, where they are thought to maintain homeostasis and limit immunopathology. gammadeltaT cells are postulated to exert a regulatory influence during acute allergic airway disease, but the mechanism is unknown. Although regulation of allergic airway disease has been attributed to IL-17-producing T helper (Th) 17 cells, we have found that gammadeltaT cells represent the major source of IL-17 in the allergic lung. OBJECTIVES The aim of this study was to determine the contribution of these IL-17-producing gammadeltaT cells to regulation of allergic airway inflammation. METHODS Flow cytometry revealed that IL-17-producing gammadeltaT cells are more prevalent than IL-17(+)alphabetaT cells (Th17) in a murine model of ovalbumin-induced allergic inflammation. MEASUREMENTS AND MAIN RESULTS Transfer of gammadeltaT cells at the peak of acute allergic responses ameliorated airway hyperresponsiveness with a corresponding acceleration in the resolution of eosinophilic and Th2-driven inflammation. Conversely, functional blockade of gammadeltaT cells led to exacerbation of injury. Neither treatment changed pulmonary Th17 cell numbers. Moreover, transfer of Th17 cells had no effect on disease outcome. Importantly, IL-17-deficient gammadeltaT cells were unable to promote resolution of injury. These data identify IL-17-producing gammadeltaT cells as key regulators of the allergic response in vivo. CONCLUSIONS This unfolds a new perspective for the understanding of gammadeltaT cell function with regard to innate regulation of the adaptive immune responses, emphasizing that resolution of responses are important in determining the outcome of acute inflammatory episodes as well as for maintenance of tissue integrity and homeostasis.
Adherence to combination antiretroviral therapies in HIV patients of low health literacy

AbstractOBJECTIVE: To test the significance of health literacy relative to other predictors of adherence to treatment for HIV and AIDS. PARTICIPANTS: Community sample of HIV-seropositive men (n=138) and women (n=44) currently taking a triple-drug combination of antiretroviral therapies for HIV infection; 60% were ethnic minorities, and 73% had been diagnosed with AIDS. MEASUREMENTS: An adapted form of the Test of Health Literacy in Adults (TOFHLA), a comprehensive health and treatment interview that included 2-day recall of treatment adherence and reasons for nonadherence, and measures of substance abuse, social support, emotional distress, and attitudes toward primary care providers. MAIN RESULTS: Multiple logistic regression showed that education and health literacy were significant and independent predictors of 2-day treatment adherence after controlling for age, ethnicity, income, HIV symptoms, substance abuse, social support, emotional distress, and attitudes toward primary care providers. Persons of low literacy were more likely to miss treatment doses because of confusion, depression, and desire to cleanse their body than were participants with higher health literacy. CONCLUSIONS: Interventions are needed to help persons of low literacy adhere to antiretroviral therapies.
Arthroscopic evaluation of knee articular cartilage: a comparison with plain radiographs and magnetic resonance imaging.

OBJECTIVE To compare radiographic, magnetic resonance imaging (MRI), and outpatient direct arthroscopic evaluation of cartilage in patients with osteoarthritis (OA) of the knee. METHODS Thirty-three patients with OA of the knee were evaluated by plain weight bearing radiographs and arthroscopy using a 1.9 mm arthroscope under local anesthesia. Sixteen of these patients also had MRI of the knee performed. Knee compartments were evaluated using AP weight bearing and lateral radiographs of the knee. MRI and outpatient arthroscopic grading of cartilage were performed within 2 weeks of the plain radiographs. The MRI and arthroscopic evaluations were performed independently and were graded without knowledge of the other. RESULTS In patients in whom plain radiographs, MRI, and arthroscopy were compared, the plain radiographs and MRI significantly underestimated the extent of cartilage abnormalities. There was a moderate correlation between imaged cartilage scores and the arthroscopy scores (Pearson correlation coefficient = 0.40). The arthroscopic scores were reproducible with good intra and inter-observer reliability. The arthroscopic procedure was well tolerated and actually preferred over the MRI by the majority of patients. No significant complications were noted as a result of arthroscopy. CONCLUSIONS Our results indicate that outpatient arthroscopic evaluation is a useful method in evaluating surface cartilage abnormalities and is more sensitive in detecting these abnormalities than either plain radiographs or MRI. Outpatient arthroscopic evaluation of cartilage appears to be a safe, sensitive, and a well tolerated tool for evaluating patients with OA of the knee and may prove to be particularly useful in evaluating response to therapeutic interventions.
The Influence of Entrepreneurship Education on the Entrepreneurial Intentions of University Students in Katsina State, Nigeria

Abstract This study attempts to determine the influence of Entrepreneurship Education (EEd) on the entrepreneurial intentions of university students in Katsina State, Nigeria. The study is guided by the following specific objectives: to examine the nature of entrepreneurial education being acquired by the students to determine the extent of influence of the acquired education on the students’ entrepreneurial self-efficacy and to determine the extent of influence of the acquired education on student’s entrepreneurial mindset. Secondary and primary sources were used in generating data for the study. Using stratified and random sampling techniques, data was generated by means of a structured questionnaire administered to 400 students across the three universities in the State. Descriptive statistics as well as simple regression was used in analysing the data collected from the respondents. Findings revealed that students fairly agreed that they have acquired education in major areas of entrepreneurship encompassing creativity, innovation, and venture creation and that EEd has a significantly positive influence on their entrepreneurial self-efficacy and entrepreneurial mindset. The study recommends that university managements should devise means of an adequate follow-up of their graduates to ensure the translation of their entrepreneurial intentions into venture creation, while entrepreneurship education lecturers should pay special attention to the area of venture creation as the students do not seem to be very optimistic in their ability to translate business opportunities into business projects/ventures.
An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry.

BACKGROUND The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL Registry) was established to characterize the clinical course, treatment, and predictors of outcomes in patients with pulmonary arterial hypertension (PAH) in the United States. To date, estimated survival based on time of patient enrollment has been established and reported. To determine whether the survival of patients with PAH has improved over recent decades, we assessed survival from time of diagnosis for the REVEAL Registry cohort and compared these results to the estimated survival using the National Institutes of Health (NIH) prognostic equation. METHODS Newly or previously diagnosed patients (aged ≥ 3 months at diagnosis) with PAH enrolled from March 2006 to December 2009 at 55 US centers were included in the current analysis. RESULTS A total of 2,635 patients qualified for this analysis. One-, 3-, 5-, and 7-year survival rates from time of diagnostic right-sided heart catheterization were 85%, 68%, 57%, and 49%, respectively. For patients with idiopathic/familial PAH, survival rates were 91% ± 2%, 74% ± 2%, 65% ± 3%, and 59% ± 3% compared with estimated survival rates of 68%, 47%, 36%, and 32%, respectively, using the NIH equation. CONCLUSIONS Comprehensive analysis of survival from time of diagnosis in a large cohort of patients with PAH suggests considerable improvements in survival in the past 2 decades since the establishment of the NIH registry, the effects of which most likely reflect a combination of changes in treatments, improved patient support strategies, and possibly a PAH population at variance with other cohorts
The Effect of Early Hominin Occlusal Morphology on the Fracturing of Hard Food Items

Tooth profile plays an important role in interpretations of the functional morphology of extinct species. We tested hypotheses that australopith occlusal morphology influences the fracture force required to crack large, hard food items using a combination of physical testing and finite element analysis (FEA). We performed mechanical experiments simulating both molar and premolar biting using metal replicas of four hominin specimens representing species that differ in occlusal relief (Praeanthropus afarensis, Australopithecus africanus, Paranthropus robustus, and P. boisei). The replicas were inserted into an Instron machine and used to fracture hollow acrylic hemispheres with known material properties. These hemispheres simulate a hard and brittle food item but exhibit far less variability in size and strength than actual nuts or seeds, thereby facilitating interpretations of tooth function. Fracture forces and fracture displacements were measured, and analysis of variance revealed significant differences in fracture force and energy between specimens and tooth types. Complementing the physical testing, a nonlinear contact finite element model was developed to simulate each physical test. Experimental and FEA results showed good correspondence in most cases, and FEA identified stress concentrations consistent with mechanical models predicting that radial/median fractures are important factors in the failure of nut and seed shells. The fracture force data revealed functional similarities between relatively unworn Pr. afarensis and P. robustus teeth, and between relatively unworn A. africanus and heavily worn P. boisei teeth. These results are inconsistent with functional hypotheses, and raise the possibility that the tooth morphology of early hominins and other hard object feeders may not represent adaptations for inducing fractures in large, hard food items, but rather for resisting fractures in the tooth crown. Anat Rec, 293:594–606, 2010. © 2010 Wiley‐Liss, Inc.
MODD Mediates Deactivation and Degradation of OsbZIP46 to Negatively Regulate ABA Signaling and Drought Resistance in Rice

MODD negatively regulates OsbZIP46 activity and stability through HDAC-related chromatin remodeling and PUB70-mediated ubiquitination, respectively, to fine-tune ABA signaling and drought resistance. Plants have evolved complicated protective mechanisms to survive adverse conditions. Previously, we reported that the transcription factor OsbZIP46 regulates abscisic acid (ABA) signaling-mediated drought tolerance in rice (Oryza sativa) by modulating stress-related genes. An intrinsic D domain represses OsbZIP46 activity, but the detailed mechanism for the repression of OsbZIP46 activation remains unknown. Here, we report an OsbZIP46-interacting protein, MODD (Mediator of OsbZIP46 deactivation and degradation), which is homologous to the Arabidopsis thaliana ABSCISIC ACID-INSENSITIVE5 binding protein AFP. MODD was induced by ABA and drought stress, but the induction was much slower than that of OsbZIP46. In contrast to OsbZIP46, MODD negatively regulates ABA signaling and drought tolerance, and inhibits the expression of OsbZIP46 target genes. We found that MODD negatively regulates OsbZIP46 activity and stability. MODD represses OsbZIP46 activity via interaction with the OsTPR3-HDA702 corepressor complex and downregulation of the histone acetylation level at OsbZIP46 target genes. MODD promotes OsbZIP46 degradation via interaction with the U-box type ubiquitin E3 ligase OsPUB70. Interestingly, the D domain is required for both deactivation and degradation of OsbZIP46 via its interaction with MODD. These findings show that plants fine-tune their drought responses by elaborate regulatory mechanisms, including the coordination of activity and stability of key transcription factors.
Different Molecular/Behavioral Endophenotypes in C57BL/6J Mice Predict the Impact of OX1 Receptor Blockade on Binge-Like Ethanol Intake

Ethanol (EtOH) research has focused on stages of dependence. It is of paramount importance to more deeply understand the neurobehavioral factors promoting increased risk for EtOH binge drinking during the early stages of the addiction cycle. The first objective of this study was to evaluate whether C57BL/6J mice showing high drinking in the dark (DID) exhibit neurobehavioral traits known to contribute to EtOH binge-drinking disorders. Comparing high vs. low drinkers (HD/LD), we evaluated different types of basal anxiety-like responses, EtOH preference and sensitivity to the reinforcing properties of EtOH, and basal mRNA expression of the OX1/OX2 receptors (OX1r/OX2r) within the prefrontal cortex (PFC) and the nucleus accumbens (NAcc). Additionally, we tested binge drinking by LD/HD in response to a selective OX1r antagonist following intermittent episodes of DID (iDID). We report that DID consistently segregates two neurobehavioral endophenotypes, HD vs. LD, showing differences in neophobia and/or impulsivity/compulsivity traits. Additionally, HD mice show decreased basal OX1r and OX2r mRNA expression within the NAcc and elevated OX1r within the PFC. Exposure to several intermittent episodes of EtOH DID triggered a rapid increase in EtOH intake over time in LD mice matching that observed in HD mice. Despite HD/LD endophenotypes did not show differences in EtOH intake, they still predicted the response to a pharmacological challenge with a selective OX1r antagonist. The present data underscore the relevance of HD/LD endophenotypes stemming from DID procedures for exploring neurobehavioral processes underlying the early stages of the addiction cycle and EtOH binge-drinking disorders.
Molecular Mechanism of Membrane Docking by the Vam7p PX Domain*

The Vam7p t-SNARE is an essential component of the vacuole fusion machinery that mediates membrane trafficking and protein sorting in yeast. Vam7p is recruited to vacuoles by its N-terminal PX domain that specifically recognizes PtdIns(3)P in the bilayers, however the precise mechanism of membrane anchoring remains unclear. Here we describe a molecular basis for membrane targeting and penetration by the Vam7p PX domain based on structural and quantitative analysis of its interactions with lipids and micelles. Our results derived from in vitro binding measurements using NMR, monolayer surface tension experiments and mutagenesis reveal a multivalent membrane docking mechanism involving specific PtdIns(3)P recognition that is facilitated by electrostatic interactions and accompanying hydrophobic insertion. Both the hydrophobic and electrostatic components enhance the Vam7p PX domain association with PtdIns(3)P-containing membranes. The inserting Val70, Leu71, and Trp75 residues located next to the PtdIns(3)P binding pocket are surrounded by a basic patch, which is involved in nonspecific electrostatic contacts with acidic lipids, such as PtdSer. Substitution of the insertion residues significantly reduces the binding and penetrating power of the Vam7p PX domain and leads to cytoplasmic redistribution of the EGFP-tagged protein. The affinities of the PX domain for PtdIns(3)P and other lipids reveal a remarkable synergy within the multivalent complex that stably anchors Vam7p at the vacuolar membrane.
Serum macrophage‐derived chemokine (MDC) levels are closely related with the disease activity of atopic dermatitis

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of T cells, eosinophils and macrophages in lesional skin. Recently, macrophage‐derived chemokine (MDC)/CCL22, a CC chemokine, was identified as a selective chemoattractant for CC chemokine receptor 4 (CCR4)‐expressing cells, in addition to thymus and activation‐regulated chemokine (TARC). We have previously reported that serum TARC levels correlate with the severity of AD. In this report, we investigated the participation of MDC in AD. First, we measured serum MDC levels in 45 patients with AD, 25 patients with psoriasis vulgaris and 25 healthy controls. Serum MDC levels in AD patients were significantly higher than those in healthy controls and psoriasis patients. Furthermore, the increases in serum MDC levels in AD patients were greater in the severely affected group than in the moderate or mild groups. We compared serum MDC levels in 11 AD patients, before and after treatment, and observed a significant decrease after treatment. Moreover, the serum MDC levels significantly correlated with the Scoring AD (SCORAD) index, serum soluble (s) E‐selectin levels, serum soluble interleukin‐2 receptor (sIL‐2R) levels, serum TARC levels and eosinophil numbers in peripheral blood. Our study strongly suggests that serum MDC levels have a notable correlation with disease activity and that MDC, as well as the CC chemokine TARC, may be involved in the pathogenesis of AD.
A nonsemen copulatory fluid influences the outcome of sperm competition in Japanese quail

Sperm competition is a powerful and widespread evolutionary force that drives the divergence of behavioural, physiological and morphological traits. Elucidating the mechanisms governing differential fertilization success is a fundamental question of sperm competition. Both sperm and nonsperm ejaculate components can influence sperm competition outcomes. Here, we investigate the role of a nonsemen copulatory fluid in sperm competition. Male Japanese quail possess a gland that makes meringue‐like foam. Males produce and store foam independent of sperm and seminal fluid, yet transfer foam to females during copulation. We tested whether foam influenced the outcome of sperm competition by varying foam state and mating order in competitive matings. We found that the presence of foam from one male decreased the relative fertilization success of a rival, and that foam from a given male increased the probability he obtained any fertilizations. Mating order also affected competitive success. Males mated first fertilized proportionally more eggs in a clutch and had more matings with any fertilizations than subsequent males. We conclude that the function of foam in sperm competition is mediated through the positive interaction of foam with a male's sperm, and we speculate whether the benefit is achieved through improving sperm storage, fertilizing efficiency or retention. Our results suggest males can evolve complex strategies to gain fertilizations at the expense of rivals as foam, a copulatory fluid not required for fertilization, nevertheless, has important effects on reproductive performance under competition.
Empirical Evidence on the US Labour Market Hysteresis: New Keynesian Wage Phillips Curve (1990-2014)

Bu calismada ABD ekonomisinde dogal issizlik oranina karsi histeresi hipotezinin gecerliligi (1990:Q1-2014Q4) donemi icin arastirilmaktadir. Anaakim iktisat uzun donemde, yuksek ve yapiskan issizlik histeresi hipotezini degil, dogal orani benimsemektedir. Birim kok testleri issizlik/istihdam serilerinde duragan disilik tespit etmistir. Sonra, teorik cerceve cizilerek, “beseri sermaye” ve “iceridekiler-disaridakiler” hipotezleri de aciklanmistir. Yeni Keynesyen Ucret Phillips Egrisi (NKWPC) cercevesinde ucret enflasyonu issizlik, istihdam ve daha sonra cikti acigi ve cikti buyume orani degiskenlerine karsi tahmin edilmistir. Sonuclara gore histeresi etkisi bulunmamakta, sadece cikti buyume orani ile 2001 resesyonu esnasinda gozlenmektedir. Issizlik/istihdam serilerindeki duragan disiliga talep soklari veya isgucu piyasasi degiskenleri neden olabileceginden ekonomi politikasi tercihleri buna uygun olarak gerceklestirilmelidir: talep yonlu politikalar veya isgucu piyasasi tedbirleri.
Pharmacokinetics of thiamphenicol glycinate and its active metabolite by single and multiple intravenous infusions in healthy Chinese volunteers

Abstract 1. The aim of this study was to investigate the pharmacokinetics of thiamphenicol glycinate (TG) and thiamphenicol (TAP) after intravenous (i.v.) infusion of TG hydrochloride in healthy Chinese by evaluating the pharmacokinetic parameters, to provide clinical guidance in TG application. 2. In this double-blinded, phase I clinical trial, 24 healthy Chinese volunteers were recruited and divided into three groups which received a single dose of 500, 1000 or 1500 mg TG hydrochloride. Subjects in 500 mg group received further administrations at the same dose every 12 h for 5 days. The pharmacokinetic parameters were fitted on the basis of bi-phasic or tri-phasic plasma concentration–time profiles of TG and TAP. 3. Following a single dose of 500, 1000, 1500 mg TG hydrochloride, the AUC0–∞ of TG and TAP was 849.1 ± 100.3, 1305.2 ± 301.8, 2315.9 ± 546.9 and 4509.0 ± 565.9, 7506.5 ± 1112.4, 12 613.3 ± 2779.8 µgmL−1 min, respectively. The total clearance of TG was calculated as 0.58 ± 0.07, 0.41 ± 0.10 and 0.68 ± 0.18 L min−1. The transformed rate constant from TG to TAP was fitted as 0.153, 0.113 and 0.118 min−1, respectively. TAP was mainly excreted as unchanged form with no tendency of accumulation via kidney (71.9 ± 19.4%) with the renal clearance estimated at 0.097 L min−1. 4. The established modeling was applied successfully to evaluate the pharmacokinetics of TG and TAP, providing meaningful guidance in TG clinical application.
Contact tracing for gonorrhoea in homosexual and heterosexual men

We aimed to determine whether the success of partner notification for gonorrhoea in men was affected by sexual orientation. Analysis of standard clinic and health adviser records of all male patients found to be infected with gonorrhoea between October 1992 and September 1993 were carried out. Of the 278 cases of gonorrhoea in men, 9% (25) were acquired through homosexual intercourse and 91% (253) by heterosexual contact. Fifteen per cent (24) of Caucasians were homosexual but only 0.9% (1) of Afro-Caribbeans were. The mean number of contacts was 1.36 for homosexuals and 1.38 for heterosexuals. Contact information was given by 55% of heterosexuals and 48% of homosexuals. The proportion of acknowledged contacts attending was 38% for homosexuals and 56% for heterosexuals (P=0.054). Fifty-two per cent of homosexuals and 59% of heterosexuals had at least one contact attend. Data analysis on Caucasians only showed Caucasian gay men had a higher mean number of contacts (1.38) than Caucasian heterosexuals (1.28). Caucasian homosexuals had a lower proportion of contacts attending (40% vs 77%) (P=0.05), 54% of homosexual men and 60% of heterosexual men had at least one contact attending (P=0.74). There is a trend for partner notification to be less successful in homosexual men when all ethnic groups are considered together. In Caucasian men with gonorrhoea, homosexuals have a greater number of partners than heterosexuals and have a lower proportion of total contacts attending but there is no difference in the proportion having at least one contact attending. Data on sexual orientation and ethnicity should be reported in studies assessing efficacy of contact tracing.