Miracle-dz/UniFAR-FTUs huggingface dataset:
Thymic T cell anergy in autoimmune nonobese diabetic mice is mediated by deficient T cell receptor regulation of the pathway of p21ras activation

Thymic T cell anergy, as manifested by thymocyte proliferative unresponsiveness to antigens expressed in the thymic environment, is commonly believed to mediate the acquisition of immunological self- tolerance. However, we previously found that thymic T cell anergy may lead to the breakdown of tolerance and predispose to autoimmunity in nonobese diabetic (NOD) mice. Here, we show that NOD thymic T cell anergy, as revealed by proliferative unresponsiveness in vitro after stimulation through the T cell receptor (TCR), is associated with defective TCR-mediated signal transduction along the PKC/p21ras/p42mapk pathway of T cell activation. PKC activity is reduced in NOD thymocytes. Activation of p21ras is deficient in quiescent and stimulated NOD T cells, and this is correlated with a significant reduction in the tyrosine phosphorylation of p42mapk, a serine/threonine kinase active downstream of p21ras. Treatment of NOD T cells with a phorbol ester not only enhances their p21ras activity and p42mapk tyrosine phosphorylation but also restores their proliferative responsiveness. Since p42mapk activity is required for progression through to S phase of the cell cycle, our data suggest that reduced tyrosine phosphorylation of p42mapk in stimulated NOD T cells may abrogate its activity and elicit the proliferative unresponsiveness of these cells.
Transcriptional and proteomic profiling of flatfish (Solea senegalensis) spermatogenesis

The Senegalese sole (Solea senegalensis) is a marine flatfish of high economic value and a target species for aquaculture. The efforts to reproduce this species in captivity have been hampered by the fact that farmed males (F1) often show lower sperm production and fertilization capacity than wild‐type males (F0). Our knowledge on spermatogenesis is however limited to a few studies. In a previous work, we identified by 2‐D DIGE several potential protein markers in testis for the poor reproductive performance of F1 males. Therefore, the objectives of the present study were, first, to investigate changes in genes and proteins expressed in the testis throughout spermatogenesis in F0 males by using a combination of transcriptomic and proteomic approaches and, second, to further compare the testis proteome between late spermatogenic stages of F0 and F1 fish to identify potential indicators of hampered reproductive performance in F1 fish. We identified approximately 400 genes and 49 proteins that are differentially expressed during the progression of spermatogenesis and that participate in processes such as transcriptional activation, the ubiquitin–proteasome system, sperm maturation and motility or cytoskeletal remodeling. Interestingly, a number of these proteins differed in abundance between F0 and F1 fish, pointing toward alterations in cytoskeleton, sperm motility, the ubiquitin–proteasome system and the redox state during spermiogenesis as possible causes for the decreased fertility of F1 fish.
Comparison of SSM/I and AMSR-E Sea Ice Concentrations With ASPeCt Ship Observations Around Antarctica

We compare passive microwave (PM)-derived sea ice concentrations (SIC) with more than 21 600 ship-based observations (OBS) of SIC acquired around Antarctica. PM SIC are derived from SSM/I-SSMIS and AMSR-E measurements in 1991-2009 and 2002-2010, respectively, with the ARTIST Sea Ice (ASI), Comiso Bootstrap (BST), NASA-Team (NT), enhanced NASA-Team (NT2), and EUMETSAT OSI-SAF (OSI) algorithm. We compare correlation coefficients (CC), RMSDs, and biases, separately for SSM/I-SSMIS data for algorithms ASI, BST, OSI, and NT, and for AMSR-E data for algorithms ASI, BST, and NT2. With OBS SIC and PM SIC being on fundamentally different spatiotemporal scales, we develop a new colocation approach using daily-average along-ship-track SIC values. CC between OBS SIC and PM SIC agree within their uncertainty for all algorithms and sensors. Year-round CC values are around 0.85 (AMSR-E) and 0.82 (SSM/I); CC values are similar during summer, but drop significantly during winter. Year-round RMSD values range from 13% (BST and OSI) to 17% (NT) for SSM/I and from 12% (BST) to 16% (NT2) for AMSR-E. RMSD values are similar during summer, but decrease for winter (BST: 8% for AMSR-E, 10% for SSM/I). For AMSR-E, biases are below 0.5% for BST and ASI, but between 5% (winter) and 9% (summer) for NT2. For SSM/I, biases are smaller during summer, -0.7% for BST to -7.8% for NT, than winter, -3.6% for BST to -13.9% for NT. Overall, best agreement between OBS and PM SIC is found for BST.
Olympic Weightlifting and Plyometric Training With Children Provides Similar or Greater Performance Improvements Than Traditional Resistance Training

Abstract Chaouachi, A, Hammami, R, Kaabi, S, Chamari, K, Drinkwater, EJ, and Behm, DG. Olympic weightlifting and plyometric training with children provides similar or greater performance improvements than traditional resistance training. J Strength Cond Res 28(6): 1483–1496, 2014—A number of organizations recommend that advanced resistance training (RT) techniques can be implemented with children. The objective of this study was to evaluate the effectiveness of Olympic-style weightlifting (OWL), plyometrics, and traditional RT programs with children. Sixty-three children (10–12 years) were randomly allocated to a 12-week control OWL, plyometric, or traditional RT program. Pre- and post-training tests included body mass index (BMI), sum of skinfolds, countermovement jump (CMJ), horizontal jump, balance, 5- and 20-m sprint times, isokinetic force and power at 60 and 300°·s−1. Magnitude-based inferences were used to analyze the likelihood of an effect having a standardized (Cohen's) effect size exceeding 0.20. All interventions were generally superior to the control group. Olympic weightlifting was >80% likely to provide substantially better improvements than plyometric training for CMJ, horizontal jump, and 5- and 20-m sprint times, whereas >75% likely to substantially exceed traditional RT for balance and isokinetic power at 300°·s−1. Plyometric training was >78% likely to elicit substantially better training adaptations than traditional RT for balance, isokinetic force at 60 and 300°·s−1, isokinetic power at 300°·s−1, and 5- and 20-m sprints. Traditional RT only exceeded plyometric training for BMI and isokinetic power at 60°·s−1. Hence, OWL and plyometrics can provide similar or greater performance adaptations for children. It is recommended that any of the 3 training modalities can be implemented under professional supervision with proper training progressions to enhance training adaptations in children.
Akt signalling through GSK‐3β, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy

Skeletal muscle size is tightly regulated by the synergy between anabolic and catabolic signalling pathways which, in humans, have not been well characterized. Akt has been suggested to play a pivotal role in the regulation of skeletal muscle hypertrophy and atrophy in rodents and cells. Here we measured the amount of phospho‐Akt and several of its downstream anabolic targets (glycogen synthase kinase‐3β (GSK‐3β), mTOR, p70s6k and 4E‐BP1) and catabolic targets (Foxo1, Foxo3, atrogin‐1 and MuRF1). All measurements were performed in human quadriceps muscle biopsies taken after 8 weeks of both hypertrophy‐stimulating resistance training and atrophy‐stimulating de‐training. Following resistance training a muscle hypertrophy (∼10%) and an increase in phospho‐Akt, phospho‐GSK‐3β and phospho‐mTOR protein content were observed. This was paralleled by a decrease in Foxo1 nuclear protein content. Following the de‐training period a muscle atrophy (5%), relative to the post‐training muscle size, a decrease in phospho‐Akt and GSK‐3β and an increase in Foxo1 were observed. Atrogin‐1 and MuRF1 increased after the hypertrophy and decreased after the atrophy phases. We demonstrate, for the first time in human skeletal muscle, that the regulation of Akt and its downstream signalling pathways GSK‐3β, mTOR and Foxo1 are associated with both the skeletal muscle hypertrophy and atrophy processes.
Changes in antibiotic resistance rates of invasive Haemophilus influenzae isolates in England and Wales over the last 20 years.

OBJECTIVES The aim of this study was to determine trends in antibiotic resistance profiles of invasive clinical Haemophilus influenzae isolates over the last 20 years. METHODS Microbiology laboratories throughout England and Wales regularly submit invasive H. influenzae isolates to the Health Protection Agency for serotyping and antimicrobial susceptibility testing. Antimicrobial resistance was defined using the British Society for Antimicrobial Chemotherapy criteria (http://bsac.org.uk). All H. influenzae isolates from blood and cerebrospinal fluid (CSF) cultures between January 1985 and December 2004 were included. RESULTS Over the 20 year study period, 6805 H. influenzae isolates from blood (n = 4932, 72.5%) and CSF (n = 1873, 27.5%) were obtained. Over half the isolates (3736/6805, 54.9%) were identified as Hib, 38.9% (n = 2644) as non-capsulated and 6.2% (n = 425) as other capsulated serotypes. Resistance to ampicillin was highest at 16.2%, followed by trimethoprim (7.7%), tetracycline (1.8%) and chloramphenicol (1.2%). All isolates were susceptible to cefotaxime and only four (0.06%) were resistant to rifampicin. When analysing trends, chloramphenicol and tetracycline resistance rates have remained low since the late 1980s. Ampicillin resistance increased slowly until the mid-1990s and then gradually declined to its lowest rate of 11.6% in 2004. Resistance to trimethoprim initially fell from 10% in 1985 to 1.8% in 1989, but has continued to rise since then to 11.9% in 2004. In a logistic regression model, year of isolate (P < 0.001), non-capsulated H. influenzae (P < 0.001) and younger age (P = 0.004) remained independently associated with trimethoprim resistance. CONCLUSIONS Rifampicin and cefotaxime remain highly effective against all invasive H. influenzae isolates. Resistance to ampicillin, chloramphenicol and tetracycline has declined over the past 10 years, but trimethoprim resistance continues to increase rapidly. This finding requires further study but may reflect increased use of trimethoprim in the childhood population.
Cardiac and vascular effects of chronic angiotensin converting enzyme inhibition at subantihypertensive doses

Aim We performed two sets of experiments in order to prevent or to regress cardiac and vascular hypertrophy, using antihypertensive and subantihypertensive doses of the angiotensin converting enzyme inhibitor zabicipril. Methods and results Spontaneously hypertensive rats (SHR) begin to develop hypertension at less than 4 weeks of age and reach stable hypertension levels after 12–14 weeks. The blood pressure increase is accompanied by the development of cardiac and vascular hypertrophy. Treatment of SHR in utero and up to the age of 20 weeks with an antihypertensive dose of zabicipril (1 mg/kg per day) not only prevented the development of high blood pressure but also the development of cardiac and vascular hypertrophy. This effect was demonstrated by a significant decrease in left ventricular weight and the number of smooth muscle cell layers in the vascular media, media thickness and the media:lumen ratio in mesenteric arteries. In contrast, antihypertensive treatment with the Ca2+ antagonist verapamil (100 mg/kg per day) and the subantihypertensive dose of zabicipril (0.01 mg/kg per day) did not affect the development of cardiac and vascular hypertrophy. We found a significant increase in the length and surface density of myocardial capillaries after treatment with zabicipril at 1 mg/kg per day, indicating that the capillary density had improved and therefore that the oxygen supply of the heart was improved. Similar findings were observed with the low dose of zabicipril in SHR, although these rats had high blood pressure and cardiac and vascular hypertrophy. Conclusions Treatment of adult SHR for 16 weeks with zabicipril at 1 mg/kg per day completely normalized their blood pressure levels. This effect was accompanied by a regression of left ventricular but not of vascular hypertrophy. Treatment with an antihypertensive dose of verapamil or with a subantihypertensive dose of zabicipril had no effect on cardiac and vascular hypertrophy.
Resistance to chloramphenicol and metronidazole in anaerobic bacteria.

This paper describes two quite different mechanisms of resistance to clinically important antimicrobial agents in anaerobic bacteria, which also represent two distinct genetic processes. The first is resistance to chloramphenicol (Cm) in Bacteroides species (in particular, Bacteroides fragilis) and Clostridium perfringens, which arises due to the enzymic inactivation of the drug by acetylation. When Cm resistance occurs in other genera, it is typically plasmid determined; it is also plasmid associated in Cm-resistant strains of Cl. perfringens (Sebald and Brfort, 1975) and B. ochraceus (Guiney and Davis, 1978). The second is resistance to a group of antimicrobial agents, the 5-nitroimidazoles, which includes metronidazole (Mz) and tinidazole (Tz). In this case, resistance in strains of B. fragilis and Cl. perfringens is associated with a change in the biochemical pathway normally involved in activation of the drugs. This is a result of a chromosomal mutation which can be induced by treatment with mutagens such as N-methyl-N'-nitro N-nitrosoguanidine (MNNG) (Britz & Wilkinson, 1979). © 1981 The British Society for Antimicrobial Chemotherapy. All Rights Reserved.
Dietary Fat, Tamoxifen Use and Circulating Sex Hormones in Postmenopausal Breast Cancer Survivors

Evidence is inconsistent regarding whether dietary fat influences sex hormone concentrations. This issue is important for breast cancer survivors since clinical recommendations suggest maintaining low hormone levels primarily via pharmacologic agents. This study examines associations between dietary fat and circulating sex hormones among participants in the Health, Eating, Activity and Lifestyle (HEAL) Study, a cohort of breast cancer survivors ( N = 511). During a postdiagnosis interview, detailed data were collected on diet, physical activity, lifestyle habits, and medication use (including tamoxifen). Staff measured height and weight and collected fasting bloods. Multivariate linear regression modeled associations of dietary fat with serum sex hormones. Among women using tamoxifen, we observed modest inverse associations of dietary fat with estrone ( P < 0.01), estradiol ( P < 0.05), testosterone ( P < 0.01), free testosterone ( P < 0.01), and DHEA ( P < 0.01) for higher vs. lower fat intake; but there was no evidence for a trend. Associations were consistent across measures (percent energy from fat, total, saturated, and polyunsaturated fat), and modest effect modification was observed between fat intake and tamoxifen in relation to hormones. Among women not using tamoxifen, fat intake was not associated with hormone concentrations. Further work is needed to confirm the findings and to understand the clinical implications of these observations.
Benefits of Retention in Methadone Maintenance and Chronic Medical Conditions as Risk Factors for Premature Death Among Older Heroin Addicts

Background Methadone maintenance treatment reduces rates of premature mortality in heroin addicts. However, few published studies have addressed the effectiveness of treatment, mortality rates, or causes of death in older (geriatric) patients maintained on methadone. Identifying risk factors for premature mortality and potential targets for early intervention may reduce rates of premature mortality in older patients maintained on methadone. Methods We conducted a retrospective chart review for patients enrolled in the methadone maintenance program at the Atlanta Veterans Affairs Medical Center. We reviewed the charts of 91 patients and collected the following information: demographics (age, gender, marital status, and race); composite score at admission on the Addiction Severity Index (ASI); most recent ASI score for alcohol use, drug use, and medical, psychiatric, family, legal, and employment problems; results of urine drug screens for opiates, cocaine, and benzodi-azepines (first 4 screens after admission and last 4 screens); dose and duration of methadone treatment; HIV and hepatitis B and C status; tobacco smoking; presence of diabetes mellitus, hypertension, heart disease, chronic obstructive pulmonary disease, or cancer; history of intravenous drug use; andmissed primary care appointments (last five appointments). Results A statistically significant association was found between diabetes mellitus and between liver and gastrointestinal cancer and premature mortality in this sample of older patients maintained on methadone (OR=30.79, P=0.008 for diabetes mellitus; OR=19.91, P=0.017 for cancer). Patients who remained in treatment showed statistically significant improvement in ASI scores for problems related to drug use and for psychiatric, medical, and legal problems. They showed a nonsignificant trend toward reduction of problems associated with alcohol use. The group of patients who dropped out of methadone treatment did not show statistically significant improvement on any area of the ASI except family problems. The group who remained in treatment also showed a statistically significant reduction in drug use when results of the first four and last four urine drug screens for opiates, cocaine, and benzodiazepines were compared (P<0.0001 for opiates and cocaine, P=0.02 for benzodiazepines). On the other hand, the group who dropped out of methadone treatment did not show any statistically significant reduction in drug use based on urine screens (P=0.05 for opiates, P=0.38 for cocaine, and P=0.53 for benzodiazepines). Conclusions The results presented here suggest potential targets for intervention related to lifestyle risk factors and comorbid medical conditions, such as nicotine dependence and diabetes mellitus, that may have the potential to improve health outcomes for older patients with opioid dependence.
The impact of valve surgery on short- and long-term mortality in left-sided infective endocarditis: do differences in methodological approaches explain previous conflicting results?

AIMS The aim of this study was to evaluate the effect of valve surgery (VS) in infective endocarditis (IE) on 5-year mortality and to evaluate whether conflicting results reported by previous studies could be due to differences in their methodological approaches. METHODS AND RESULTS Four hundred and forty-nine patients with a definite left-sided IE were selected from a prospective, population-based study. Association between VS and 5-year mortality was examined with a Cox model. To determine the impact of different methodological approaches, we also analysed the relationship between VS and mortality in our database, according to each method used in the five previous studies. Valve surgery was performed in 240 patients (53%). It was associated with an increase in short-term mortality [within the first 14 post-operative days; adjusted hazard ratio (HR), 3.69; 95% confidence interval (CI), 2.17-6.25; P<0.0001] and a decrease in long-term mortality (adjusted HR, 0.55; 95% CI, 0.35-0.87; P=0.01). At least 188 days of follow-up were required for VS to provide an overall survival advantage. When applying each study's method to our database, we obtained results similar to those reported. CONCLUSION Previous conflicting results appear to be related to differences in statistical methods. When using appropriate models, we found that VS was significantly associated with reduced long-term mortality.
A Li-Ion Battery Charge Protocol with Optimal Aging-Quality of Service Trade-off

The reduction of usable capacity of rechargeable batteries can be mitigated during the charge process by acting on some stress factors, namely, the average state-of-charge (SOC) and the charge current. Larger values of these quantities cause an increased degradation of battery capacity, so it would be desirable to keep both as low as possible, which is obviously in contrast with the objective of a fast charge. However, by exploiting the fact that in most battery-powered systems the time during which it is plugged for charging largely exceeds the time required to charge, it is possible to devise appropriate charge protocols that achieve a good balance between fast charge and aging. In this paper we propose a charge protocol that, using an accurate estimate of the charging time of a battery and the statistical properties of the charge/discharge patterns, yields an optimal trade-off between aging and quality of service. The latter is measured in terms of the distance of the actual SOC from 100% at the end of the charge phase. Results show that the present method improves significantly over other similar protocols proposed in the literature.
Minocycline in lepromatous leprosy.

Twelve patients were treated with three dose levels of minocycline for 30 days, primarily to detect the dose-related effects on Mycobacterium leprae viability, followed by another 5 months of daily minocycline for overall efficacy and persistence of clinical and antibacterial effects. Subsequently, the patients were given standard WHO/MDT chemotherapy for multibacillary leprosy. Clinical improvement was recognizable during the first month, occurring much earlier among those on minocycline 200 mg daily than those who received minocycline 100 mg daily. A similar change also was observed in one patient 11 days after three daily doses of 100 mg of minocycline. At the end of 6 months, all patients were clinically improved with a slight reduction in the average bacterial index (BI) and logarithmic index of bacilli in biopsy (LIB). The effects of minocycline on viability by mouse foot pad inoculation and palmitic acid oxidation assays were noted beginning at 10 to 14 days of daily dosing and becoming more definite after 30 days of treatment. Both tests correlated fairly well. Doses of 200 mg daily did not appear to be more efficient than minocycline 100 daily. Phenolic glycolipid-I (PGL-I) antigen determinations done on some patients during the first month remained positive and did not correlate with changes in viability results. At the end of 6 months, after 5 months of 100 mg of minocycline monotherapy, no viable organisms could be demonstrated by mouse foot pad inoculation and palmitic acid oxidation assays; assays for PGL-I antigen were all negative. (ABSTRACT TRUNCATED AT 250 WORDS)