Miracle-dz/UniFAR-FTUs huggingface dataset:
The Critical Role of Proteolytic Relay through Cathepsins B and E in the Phenotypic Change of Microglia/Macrophage

Proteinase cascades are part of the basic machinery of neuronal death pathways. Neuronal cathepsin B (CatB), a typical cysteine lysosomal protease, plays a critical role in neuronal death through lysosomal leakage or excessive autophagy. On the other hand, much attention has been paid to microglial CatB in neuronal death. We herein show the critical role of proteolytic relay through microglial CatB and CatE in the polarization of microglia/macrophages in the neurotoxic phenotype, leading to hypoxia/ischemia (HI)-induced hippocampal neuronal damage in neonatal mice. HI caused extensive brain injury in neonatal wild-type mice, but not in CatB−/− mice. Furthermore, HI-induced polarization of microglia/macrophages in the neurotoxic phenotype followed by the neuroprotective phenotype in wild-type mice. On the other hand, microglia/macrophages exhibited only the early and transient polarization in the neuroprotective phenotype in CatB−/− mice. CA-074Me, a specific CatB inhibitor, significantly inhibited the neuronal death of primary cultured hippocampal neurons induced by the conditioned medium from cultured microglia polarized in the neurotoxic phenotype. Furthermore, CA-074Me prevented the activation of nuclear factor-κB (NF-κB) in cultured microglia by inhibiting autophagic inhibitor of κBα degradation following exposure to oxygen–glucose deprivation. Rather surprisingly, CatE increased the CatB expression after HI by the liberation of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) from microglia through the proteasomal pathway. A significant increase in CatB and CatE levels was found exclusively in microglia/macrophages after HI. Thus, a proteolytic relay through the early CatE/TRAIL-dependent proteosomal and late CatB-dependent autophagic pathways for NF-κB activation may play a critical role in the polarization of microglia/macrophages in the neurotoxic phenotype. SIGNIFICANCE STATEMENT Proteinase cascades are part of the basic machinery of neuronal death pathways. Cathepsin B, a typical cysteine lysosomal protease, plays a critical role in neuronal death through lysosomal leakage or excessive autophagy in neurons. On the other hand, much attention has been also paid to the role of microglial cathepsin B in neuronal death. In this study, using in vivo and in vitro models of relevance to brain ischemia, we found a critical role of proteolytic relay through cathepsin B and cathepsin E in the neurotoxic polarization of microglia/macrophages, which is responsible for aggravation of hypoxia/ischemia-induced neuronal injury. These findings suggest orally active selective inhibitors of cathepsin B or cathepsin E as promising pharmacological agents for the treatment of ischemic brain injury.
Controlling the relative entropy evolution for classical and quantum systems

We study the relative entropy of physical systems (classical, thermodynamical and quantum systems) with Markovian evolution and subject to an external controlling force. We derive some basic results on the relative entropy production rate that considerably extend known ones. Applications to macromolecular cooling and to modifying the evolution towards equilibrium are sketched.
Impact of family and gender on career goals: results of a national survey of 4586 surgery residents.

OBJECTIVE To determine how marriage, children, and gender influence US categorical general surgery residents' perceptions of their profession and motivations for specialty training. DESIGN Cross-sectional national survey administered after the January 2008 American Board of Surgery In-service Training Examination. SETTING Two hundred forty-eight US general surgery residency programs. PARTICIPANTS All US categorical general surgery residents. INTERVENTIONS We evaluated demographic characteristics with respect to survey responses using the chi(2) test, analysis of variance, and multivariate logistic regression. Interaction terms between variables were assessed. MAIN OUTCOME MEASURES Perceptions of respondents regarding the future of general surgery and the role of specialty training in relation to anticipated income and lifestyle. RESULTS The survey response rate was 75.0% (4586 respondents). Mean age was 30.6 years; 31.7% were women, 51.3% were married, and 25.4% had children. Of the respondents, 28.7% believed general surgery is becoming obsolete (30.1% of men and 25.9% of women; P = .004), and 55.1% believed specialty training is necessary for success (56.4% of men and 52.7% of women; P = .02). Single residents and residents without children were more likely to plan for fellowship (59.1% single vs 51.9% married, P < .001; 57.0% with no children vs 50.1% with children, P < .001). In our multivariate analyses, male gender was an independent predictor of worry that general surgery is becoming obsolete (P = .003). Female residents who were single or had no children tended to identify lifestyle rather than income as a motivator for specialty training. CONCLUSION Marital status, children, and gender appear to have a powerful effect on general surgery residents' career planning.
How and When Should NSAIDs Be Used for Preventing Post-ERCP Pancreatitis? A Systematic Review and Meta-Analysis

Background Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be efficacious to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, the target patients, the type of NSAID, the route of administration and the time of drug delivery remain unclear, as well as the potential efficacy in reducing the severity of pancreatitis, length of hospital stay and mortality. The objective of the study was to evaluate these questions by performing a systematic review and meta-analysis. Methods Multiple searches were performed in the main databases. Randomized controlled trials (RCTs) comparing NSAIDs vs. placebo in the prevention of post-ERCP pancreatitis were included. Primary endpoint of the study was the efficacy for pancreatitis prevention. Sub-analyses were performed to determine the risk reduction in high and low risk patients, and to define optimal time, route of administration, and type of NSAID. Secondary endpoints were safety, moderate to severe pancreatitis prevention and reduction of hospital stay and mortality. Results Nine RCTs enrolling 2133 patients were included. The risk of pancreatitis was lower in the NSAID group than in the placebo group (RR 0.51; 95%CI 0.39–0.66). The number needed to treat was 14. The risk of moderate to severe pancreatitis was also lower in the NSAID group. (RR 0.46; 95%CI 0.28–0.76). No adverse events related to NSAID use were reported. NSAIDs were effective in both high-risk and unselected patients (RR 0.53; 95%CI 0.30–0.93 and RR 0.57; 95%CI 0.37–0.88). In the subanalyses, only rectal administration of either indomethacin (RR 0.54; 95%CI 0.38–0.75) or diclofenac (RR 0.42; 95%CI 0.21–0.84) was shown to be effective. There were not enough data to perform a meta-analysis in hospital stay reduction. No deaths occurred. Conclusion A single rectal dose of indomethacin or diclofenac before or immediately after ERCP is safe and prevents procedure-related pancreatitis both in high risk and in unselected patients.
CD4+/CD8+ ratio, age, and risk of serious noncommunicable diseases in HIV-infected adults on antiretroviral therapy

Objective:In virologically suppressed HIV-infected adults, noncommunicable diseases (NCDs) have been associated with immune senescence and low CD4+/CD8+ lymphocyte ratio. Age differences in the relationship between CD4+/CD8+ ratio and NCDs have not been described. Design:Observational cohort study. Methods:We assessed CD4+/CD8+ ratio and incident NCDs (cardiovascular, cancer, liver, and renal diseases) in HIV-infected adults started on antiretroviral therapy between 1998 and 2012. Study inclusion began once patients maintained virologic suppression for 12 months (defined as baseline). We examined age and baseline CD4+/CD8+ ratio and used Cox proportional hazard models to assess baseline CD4+/CD8+ ratio and NCDs. Results:This study included 2006 patients. Low baseline CD4+/CD8+ ratio was associated with older age, male sex, and low CD4+ lymphocyte counts. In models adjusting for CD4+ lymphocyte count, CD4+/CD8+ ratio was inversely associated with age (P < 0.01). Among all patients, 182 had incident NCDs, including 46 with coronary artery disease (CAD) events. CD4+/CD8+ ratio was inversely associated with risk of CAD events [adjusted HR per 0.1 increase in CD4+/CD8+ ratio = 0.87, 95% confidence interval (CI): 0.76–0.99, P = 0.03]. This association was driven by those under age 50 years (adjusted HR 0.83 [0.70–0.97], P = 0.02) vs. those over age 50 years (adjusted HR = 0.96 [0.79–1.18], P = 0.71). CD4+/CD8+ ratio was not significantly associated with incident noncardiac NCDs. Conclusions:Higher CD4+/CD8+ ratio after 1 year of HIV virologic suppression was independently predictive of decreased CAD risk, particularly among younger adults. Advanced immune senescence may contribute to CAD events in younger HIV patients on antiretroviral therapy.
Effects of physical exercise on depression, neuroendocrine stress hormones and physiological fitness in adolescent females with depressive symptoms.

BACKGROUND Regular physical exercise may improve a variety of physiological and psychological factors in depressive persons. However, there is little experimental evidence to support this assumption for adolescent populations. We conducted a randomized controlled trial to investigate the effect of physical exercise on depressive state, the excretions of stress hormones and physiological fitness variables in adolescent females with depressive symptoms. METHODS Forty-nine female volunteers (aged 18-20 years; mean 18.8 +/- 0.7 years) with mild-to-moderate depressive symptoms, as measured by the Centre for Epidemiologic Studies Depression (CES-D) scale, were randomly assigned to either an exercise regimen or usual daily activities for 8 weeks. The subjects were then crossed over to the alternate regimen for an additional 8-week period. The exercise program consisted of five 50-min sessions per week of a group jogging training at a mild intensity. The variables measured were CES-D rating scale, urinary cortisol and epinephrine levels, and cardiorespiratory factors at rest and during exercise endurance test. RESULTS After the sessions of exercise the CES-D total depressive score showed a significant decrease, whereas no effect was observed after the period of usual daily activities (ANOVA). Twenty-four hour excretions of cortisol and epinephrine in urine were reduced due to the exercise regimen. The training group had a significantly reduced resting heart rate and increased peak oxygen uptake and lung capacity. CONCLUSIONS The findings of this study suggest that a group jogging exercise may be effective in improving depressive state, hormonal response to stress and physiological fitness of adolescent females with depressive symptoms.
Ceria–Zirconia Particles Wrapped in a 2D Carbon Envelope: Improved Low-Temperature Oxygen Transfer and Oxidation Activity

Engineering the interface between different components of heterogeneous catalysts at nanometer level can radically alter their performances. This is particularly true for ceria-based catalysts where the interactions are critical for obtaining materials with enhanced properties. Here we show that mechanical contact achieved by high-energy milling of CeO2–ZrO2 powders and carbon soot results in the formation of a core of oxide particles wrapped in a thin carbon envelope. This 2D nanoscale carbon arrangement greatly increases the number and quality of contact points between the oxide and carbon. Consequently, the temperatures of activation and transfer of the oxygen in ceria are shifted to exceptionally low temperatures and the soot combustion rate is boosted. The study confirms the importance of the redox behavior of ceria-zirconia particles in the mechanism of soot oxidation and shows that the organization of contact points at the nanoscale can significantly modify the reactivity resulting in unexpected properties and functionalities.
An experimental evaluation of the use of C 3 d 13 C plant tissue as a proxy for the paleoatmospheric d 13 CO 2 signature of air

[1] Previous work suggests that the relationship between the carbon isotope composition of air (dCa) and plant leaf tissue (dCp) can be used to track changes in the carbon isotope composition of paleo-atmospheric CO2. Here we test this assertion in a series of experiments using the model plant Arabidopsis thaliana grown under a range of atmospheric CO2 concentrations relevant to geologic time (380, 760, 1000, 1500, 2000 and 3000 ppm). Nested within these CO2 experiments water availability was controlled (giving two sets of experimental plants; low and high water treatment at each CO2 concentration) to manipulate stomatal opening, a key process governing carbon fixation and isotope discrimination. Results show a highly significant relationship between dCa and d Cp under both experimental water treatments. To test the utility of d Cp to predict dCa we compare calculated d Ca to measured values of d Ca. These data show that although there is a significant relationship between calculated and measured dCa, there is disparity between the two values of dCa and a large difference between calculated values under different water treatments even when grown in a common CO2 concentration. These results demonstrate that environmental factors that alter stomatal opening can severely impact on the use and reliability of dCp to predict d Ca and as such, results should be interpreted with caution.
Temperature-dependent changes of chloride transport kinetics in human red cells

Chloride self-exchange in human red cells was studied between 0 degrees C and 38 degrees C. At higher temperatures the flow-tube method was used. Although the general features of chloride transport at 0 degrees C and 38 degrees C are similar, the following differences were found: (a) the maximum pH of chloride self-exchange flux was lowered 0.6 pH unit from 7.8 to 7.2 when temperature was increased from 0 degrees C to 38 degrees C; (b)the apparent half-saturation constant increased from 28 mM at 0 degrees C to 65 mM at 38 degrees C; (c) chloride transport at body temperature is slower than predicted by other investigators by extrapolation from low-temperature results. Chloride transport increased only 200 times when temperature was raised from 0 degrees C to 38 degrees C, because the apparent activation energy decreased from 30 kcal mol(-1) to 20 kcal mol(-1) above a temperature of 15 degrees C; (d) a study of temperature dependence of the slower bromide self-exchange showed that a similar change of activation energy occurred around 25 degrees C. Both in the case of Cl(-) (15 degrees C) and in the case of Br(-) (25 degrees C), critical temperature was reached when the anion self-exchange had a turnover number of about 4x10(9) ions cell (-1)s(-1); (e) inhibition of chloride transport by DIDS (4,4’- diisothiocyano-stilbene-2,2’-disulfonate)revealed that the deflection persisted at 15 degrees C at partial inhibition (66 percent) presumably because DIDS inactivated 66 percent of the transport sites. It is suggested that a less temperature- dependent step of anion exchange becomes rate limiting at the temperature where a critical turnover number is reached.
Resources and geology of coalbed methane in China: a review

ABSTRACT China produced 17.1 billion cubic meters (BCM) of methane sourced from coal seams in 2015, of which 4.43 BCM is from wells drilled from the surface. This level of production is a clear indicator that China has gone into early stage large-scale coalbed methane (CBM) development. CBM resources in China have been extensively investigated since the 1980s. Research has focused on the geological controls of reservoir character. There have been significant advances over the last 37 years that have aided China’s CBM industry. CBM resources less than 2000 m in depth in China are estimated to be 36.81 trillion cubic meters, of which more than 84% occur in nine large-scale basins, such as the Qinshui, Ordos, Junggar, Qianxi, Erenhot, and Hailar. CBM accumulation and coal reservoir characteristics are controlled by the deposition, structure, coal rank, hydrology as well as other geological factors. Each basin has its own unique geological controls that influence the character of CBM reservoirs in both subtle and obvious ways. Coal reservoir geology in some basins or regions in China are still not well understood because of the complexity of the geological settings. At present, large-scale CBM production in China only occurs within the Qinshui and Ordos basins, mostly sourced from middle-to-high rank coal reservoirs. The CBM geology in other basins needs further investigation in order to achieve large-scale commercial production. To this end, the geological research in the paper should address issues such as how to stimulate economic gas flow from deep low permeability reservoirs and how best to efficiently produce from multiple horizons simultaneously. This paper summarizes these and other key issues that are significant scientific and technical challenges for the CBM industry within China.
IMPROVED PRONUNCIATION MODELING BY PROPERLY INTEGRATING BETTER APPROACHES FOR BASEFORM GENERATION , RANKING AND PRUNING

In this paper, a complete framework for pronunciation modeling process is discussed and analyzed as the integration of three individual but mutual-interactive stages, i.e., the baseform generation, baseform ranking, and baseform pruning stage. The characteristics of different techniques used in each stage and the interaction among them are then well reflected on the overall performance of pronunciation modeling. Consequently, pronunciation variation could be better handled by integrating the appropriately chosen techniques for each of the three stages. In baseform generation stage, an improved approach to automatically construct a fine word confusion table with an expanded phone-unit dictionary is proposed. In baseform ranking stage, the conventional pronunciation frequency (pf)based, our recently proposed pronunciation frequency and inverse word frequency (pf-iwf)-based, and a newly proposed iterative pf-iwf-based ranking strategies were all evaluated and analyzed. And then the nice property of pf-iwf-based strategies was verified and discussed. In baseform pruning stage, both traditional probability-based, count -based and our recently proposed entropy-based pruning criteria were investigated. Integrated with better approaches in the other two stages, say a fine confusion table and pf-iwf-based ranking, the superiority of entropy-based pruning to probability-based and count-based pruning approach was revealed and the best performance was achieved. The experiments also indicate that the evaluation of different approaches used in one stage may be shadowed by the inappropriate approaches used in other stages. For newly proposed iterative pf-iwf-based ranking, on the other hand, only marginal improvements compared to recently proposed pf-iwfbased was observed. Very probably we’ll need a larger corpus to verify more complete behavior of pronunciation modeling for this situation. Further investigation is under progress. In addition, the interaction between pronunciation modeling and language modeling is discussed on some test results with a cheating language model trained on the test data only. The potential improvement achievable with pronunciation modeling with this cheating language model is even more significant as compared to those with a fair language model. This indicated that there is still much room for improvements if the interaction between better language modeling and better pronunciation modeling can be further investigated.
Drug Resistance in Leishmaniasis

The treatment options of leishmaniasis are limited and far from satisfactory. For more than 60 years, treatment of leishmaniasis has centered around pentavalent antimonials (Sbv). Widespread misuse has led to the emergence of Sbv resistance in the hyperendemic areas of North Bihar. Other antileishmanials could also face the same fate, especially in the anthroponotic cycle. The HIV/ visceral leishmaniasis (VL) coinfected patients are another potential source for the emergence of drug resistance. At present no molecular markers of resistance are available and the only reliable method for monitoring resistance of isolates is the technically demanding in vitro amastigote-macrophage model. As the armametrium of drugs for leishmaniasis is limited, it is important that effective monitoring of drug use and response should be done to prevent the spread of resistance. Regimens of simultaneous or sequential combinations should be seriously considered to limit the emergence of resistance.
Predictors of student success in the US Army Graduate Program In Anesthesia Nursing.

The primary objective of this research was to identify cognitive and noncognitive factors that may predict student success in the US Army Graduate Program in Anesthesia Nursing. Second, the results of this study will help identify students possibly at risk for failure so that interventional measures can be developed and implemented to promote success and reduce attrition. Participants in this 3-year longitudinal, nonexperimental, prospective, descriptive study were 42 students. Cognitive and noncognitive assessment tools were used to identify predictors of success. The measure of success was defined as graduation from the program and withdrawal or relief as nonsuccess. All data were analyzed using logistic regression. Results were considered statistically significant at a P value of . 05 or less. Only 2 noncognitive factors, locus of control and trait anxiety, were statistically significant such that students with a more external locus of control and lower trait anxiety were more likely to succeed (-2 log likelihood of 33.83; overall P = .012). The findings suggest that locus of control and trait anxiety may be the most predictive indicators of success in the program. Furthermore, our findings support that noncognitive factors may be as vital as cognitive factors in predicting academic success.
Translation elicits a growth rate‐dependent, genome‐wide, differential protein production in Bacillus subtilis

Complex regulatory programs control cell adaptation to environmental changes by setting condition‐specific proteomes. In balanced growth, bacterial protein abundances depend on the dilution rate, transcript abundances and transcript‐specific translation efficiencies. We revisited the current theory claiming the invariance of bacterial translation efficiency. By integrating genome‐wide transcriptome datasets and datasets from a library of synthetic gfp‐reporter fusions, we demonstrated that translation efficiencies in Bacillus subtilis decreased up to fourfold from slow to fast growth. The translation initiation regions elicited a growth rate‐dependent, differential production of proteins without regulators, hence revealing a unique, hard‐coded, growth rate‐dependent mode of regulation. We combined model‐based data analyses of transcript and protein abundances genome‐wide and revealed that this global regulation is extensively used in B. subtilis. We eventually developed a knowledge‐based, three‐step translation initiation model, experimentally challenged the model predictions and proposed that a growth rate‐dependent drop in free ribosome abundance accounted for the differential protein production.