Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetic Factors Control Efficiencies of Cell Entry, Efficacies of Entry Inhibitors, and Mechanisms of Adaptation of Human Immunodeficiency Virus

ABSTRACT Replication of human immunodeficiency virus type 1 (HIV-1) in diverse conditions limiting for viral entry into cells frequently leads to adaptive mutations in the V3 loop of the gp120 envelope glycoprotein. This has suggested that the V3 loop limits the efficiencies of HIV-1 infections, possibly by directly affecting gp120-coreceptor affinities. In contrast, V3 loop mutations that enable HIV-1JR-CSF to use the low-affinity mutant coreceptor CCR5(Y14N) are shown here to have negligible effects on the virus-coreceptor affinity but to dramatically accelerate the irreversible conformational conversion of the envelope gp41 subunits from a three-stranded coil into a six-helix bundle. This slow step is blocked irreversibly by the inhibitor T-20. To further evaluate the role of entry rates in controlling infection efficiencies and viral adaptations, we developed methods to quantitatively measure viral entry kinetics. The virions were adsorbed by spinoculation at 4°C onto HeLa-CD4/CCR5 cell clones that either had limiting or saturating concentrations of CCR5. After warming to 37°C, the completion of entry was monitored over time by the resistance of infections to the competitive CCR5 inhibitor TAK-779. Our results suggest that the efficiency of entry of cell-attached infectious HIV-1 is principally controlled by three kinetic processes. The first is a lag phase that is caused in part by the concentration-dependent reversible association of virus with CD4 and CCR5 to form an equilibrium assemblage of complexes. Second, this assembly step lowers but does not eliminate a large activation energy barrier for a rate-limiting, CCR5-dependent conformational change in gp41 that is sensitive to blockage by T-20. The rate of infection therefore depends on the fraction of infectious virions that are sufficiently saturated with CCR5 to undergo this conformational change and on the magnitude of the activation energy barrier. Although only a small fraction of fully assembled viral complexes overcome this barrier per hour, the ensuing steps of entry are rapidly completed within 5 to 10 min. Thus, this barrier limits the overall flow rate at which the attached virions enter cells, but it has no effect on the lag time that precedes this entry flow. Third, a relatively rapid and kinetically dominant process of viral inactivation, which may partly involve endocytosis, competes with infectious viral entry. Our results suggest that the V3 loop of gp120 has a major effect on the rate-limiting coreceptor-dependent conformational change in gp41 and that adaptive viral mutations, including V3 loop mutations, function kinetically by accelerating this inherently slow step in the entry pathway.
Direct cerebral vasodilatory effects of sevoflurane and isoflurane.

BACKGROUND The effect of volatile anesthetics on cerebral blood flow depends on the balance between the indirect vasoconstrictive action secondary to flow-metabolism coupling and the agent's intrinsic vasodilatory action. This study compared the direct cerebral vasodilatory actions of 0.5 and 1.5 minimum alveolar concentration (MAC) sevoflurane and isoflurane during an propofol-induced isoelectric electroencephalogram. METHODS Twenty patients aged 20-62 yr with American Society of Anesthesiologists physical status I or II requiring general anesthesia for routine spinal surgery were recruited. In addition to routine monitoring, a transcranial Doppler ultrasound was used to measure blood flow velocity in the middle cerebral artery, and an electroencephalograph to measure brain electrical activity. Anesthesia was induced with propofol 2.5 mg/kg, fentanyl 2 micro/g/kg, and atracurium 0.5 mg/kg, and a propofol infusion was used to achieve electroencephalographic isoelectricity. End-tidal carbon dioxide, blood pressure, and temperature were maintained constant throughout the study period. Cerebral blood flow velocity, mean blood pressure, and heart rate were recorded after 20 min of isoelectric encephalogram. Patients were then assigned to receive either age-adjusted 0.5 MAC (0.8-1%) or 1.5 MAC (2.4-3%) end-tidal sevoflurane; or age-adjusted 0.5 MAC (0.5-0.7%) or 1.5 MAC (1.5-2%) end-tidal isoflurane. After 15 min of unchanged end-tidal concentration, the variables were measured again. The concentration of the inhalational agent was increased or decreased as appropriate, and all measurements were repeated again. All measurements were performed before the start of surgery. An infusion of 0.01% phenylephrine was used as necessary to maintain mean arterial pressure at baseline levels. RESULTS Although both agents increased blood flow velocity in the middle cerebral artery at 0.5 and 1.5 MAC, this increase was significantly less during sevoflurane anesthesia (4+/-3 and 17+/-3% at 0.5 and 1.5 MAC sevoflurane; 19+/-3 and 72+/-9% at 0.5 and 1.5 MAC isoflurane [mean +/- SD]; P<0.05). All patients required phenylephrine (100-300 microg) to maintain mean arterial pressure within 20% of baseline during 1.5 MAC anesthesia. CONCLUSIONS In common with other volatile anesthetic agents, sevoflurane has an intrinsic dose-dependent cerebral vasodilatory effect. However, this effect is less than that of isoflurane.
A Dynamic Global CGE Model with a GVAR-based Baseline

With one crisis every 58 months on average, statistically speaking the beginning of the next crisis would be around April 2015 and would end by March 2016. This paper documents the theoretical structure of a dynamic global CGE model, as well as illustrates the potential economic consequences of another global crisis on the world economy. The two main reasons for developing a dynamic model is (1) to identify transition paths of variables between the initial equilibrium and the post-simulation equilibrium; and (2) to incorporate the convergence speed of out-of-steady state growth paths for specific variables. The first – transition paths – are particularly useful when the study has an explicit interest in inter-temporal aspects of exogenous variables (e.g. investment phase-in) or endogenous variables (e.g. inflation pattern). The second – convergence speed – helps improve the credibility of predictions by allowing lagged adjustments to be introduced into the model (e.g. in investment and/or in the labour market). The calibration of the global dynamic model involves developing baseline growth paths for each of the regional economies that are globally consistent. Development of a world baseline include currently introducing demographic as well as real GDP projections in each region. The paper analyses the policy scenario applying interval-differentiated shocks in both the baseline and in the counterfactual simulations. This allows taking full advantage of quarterly GDP forecasts produced by our in-house global VAR model that is consistent with our set of countries.
Nitrogen and Chemical Oxygen Demand Removal from Septic Tank Wastewater in Subsurface Flow Constructed Wetlands: Substrate (Cation Exchange Capacity) Effects

The current article focuses on chemical oxygen demand (COD) and nitrogen (ammonium and nitrate) removal performance from synthetic human wastewater as affected by different substrate rocks having a range of porosities and cation exchange capacities (CECs). The aggregates included lava rock, lightweight expanded shale, meta‐basalt (control), and zeolite. The first three had CECs of 1 to 4 mequiv/100 gm, whereas the zeolite CEC was much greater (∼80 mequiv/100 gm). Synthetic wastewater was gravity fed to each constructed wetland system, resulting in a 4‐day retention time. Effluent samples were collected, and COD and nitrogen species concentrations measured regularly during four time periods from November 2008 through June 2009. Chemical oxygen demand and nitrogen removal fractions were not significantly different between the field and laboratory constructed wetland systems when corrected for temperature. Similarly, overall COD and nitrogen removal fractions were practically the same for the aggregate substrates. The important difference between aggregate effects was the zeolite's ammonia removal process, which was primarily by adsorption. The resulting single‐stage nitrogen removal process may be an alternative to nitrification and denitrification that may realize significant cost savings in practice.
The N-Terminal Region of Arabidopsis Cystathionine γ-Synthase Plays an Important Regulatory Role in Methionine Metabolism1

Cystathionine γ-synthase (CGS) is a key enzyme of Met biosynthesis in bacteria and plants. Aligning the amino acid sequences revealed that the plant enzyme has an extended N-terminal region that is not found in the bacterial enzyme. However, this region is not essential for the catalytic activity of this enzyme, as deduced from the complementation test of an Escherichia coli CGS mutant. To determine the function of this N-terminal region, we overexpressed full-length Arabidopsis CGS and its truncated version that lacks the N-terminal region in transgenic tobacco (Nicotiana tabacum) plants. Transgenic plants expressing both types of CGS had a significant higher level of Met,S-methyl-Met, and Met content in their proteins. However, although plants expressing full-length CGS showed the same phenotype and developmental pattern as wild-type plants, those expressing the truncated CGS showed a severely abnormal phenotype. These abnormal plants also emitted high levels of Met catabolic products, dimethyl sulfide and carbon disulfide. The level of ethylene, the Met-derived hormone, was 40 times higher than in wild-type plants. Since the alien CGS was expressed at comparable levels in both types of transgenic plants, we further suggest that post-translational modification(s) occurs in this N-terminal region, which regulate CGS and/or Met metabolism. More specifically, since the absence of the N-terminal region leads to an impaired Met metabolism, the results further suggest that this region plays a role in protecting plants from a high level of Met catabolic products such as ethylene.
Adenosquamous carcinoma of the stomach. A clinicopathologic analysis of 28 cases

Twenty‐eight cases of primary adenosquamous carcinoma (ASC) of the stomach were studied clinico‐pathologically. These cases were classified into two types, 16 with differentiated type adenocarcinomatous component (DAC) and 12 with undifferentiated type adenocarcinomatous component (UAC), according to the degree of glandular formation of the adenocarcinomatous elements. A large number with adeno‐carcinomas, including 131 with differentiated type and 133 with undifferentiated type, were studied as controls. As a consequence, with respect to biologic behavior, ASC with DAC was similar to the differentiated type adenocarcinoma, and ASC with UAC to the undifferentiated type adenocarcinoma. Accordingly, the behavioristic feature of ASC seemed to be governed by the adenocarcinomatous component. Histologically, a close relationship between neoplastic adenomatous and squamous components was evident in the intermingling areas, thereby suggesting a transition of both elements. In addition, a mucoepidermoid pattern was occasionally detected in the squamous component. Judging from the biologic behavior and histologic findings, the majority of ASC probably derives from the squamous metaplasia in an adenocarcinoma. The prognosis of ASC was less favorable than that of adenocarcinoma because of the more extensive tumor depth and higher frequencies of lymphatic and vascular permeations of the carcinoma cells.
The Crude Oil–Stock Market Dependence and Its Determinants: Evidence from Emerging Economies

ABSTRACT This article uses dependence-switching copulas and time-varying single copulas to characterize the world oil–stock market dependence in a broad range of emerging economies, and it then conducts a regression analysis to explore the determinants of the market dependence patterns. Our results support a positive crude oil-emerging stock market link overall. The regression results show that oil return volatility, country-specific variables (i.e., stock market volatility, petroleum production growth), and US economic policy uncertainty have positive effects on the oil–stock dependence. However, a strong US economy tends to decrease the oil–stock dependence. The robustness of these findings is confirmed.
The role of document reviews in health policy analysis among low and middle-income countries: a systematic review

Background: Health policy analysis (HPA) is a central component of health systems research (HSR) and contributes significantly to the understanding of health systems reforms including their successes and failures. In most HPA studies, document reviews feature as one of the widely used data collecting methods, especially in retrospective policy analyses. Literature indicates that a substantial number of HPA studies conducted in low and middle-income countries (LMICs) are informed by interactive data collection methods such as interviews, focus group discussions (FGDs), and observations as well as non-interactive methods such as document reviews. While efforts have been made to look into the methodologies that inform health policy analyses for LMICs in the recent years, there is a dearth in knowledge specific to document reviews and how they fit into the framework for doing health policy analysis. This paper provides findings from a qualitative systematic review of peer reviewed policy analysis studies indicating the role of document reviews; why it is employed and how this methodology is positioned and motivated for in the LMICs. Methods: Nine electronic databases were explored in search of articles with adequate information relating to the use of document reviews in HPA studies conducted in LMICs. All 28 articles included in this review were conducted in LMICs between the years 2008-2016. Articles were in English with free full text accessibility. Data extraction focused on the aims of the HPA, and the methodology and results sections in order to identify why and how document reviews were employed in HPA. Results: Twenty-eight articles from LMICs that met the inclusion criteria and examined against a quality appraisal tool were included for thematic synthesis and analysis. Reasons as to why and how health policy analysts use document reviews was directly linked to accessibility and clarity of the document and the perceived contribution of a document to the HPA process. The more accessible the documents are, the more they are likely to be
NO signaling is a key component of the root growth response to nitrate in Zea mays L.

Roots are considered to be a vital organ system of plants due to their involvement in water and nutrient uptake, anchorage, propagation, storage functions, secondary metabolite (including hormones) biosynthesis, and accumulation. Crops are strongly dependent on the availability of nitrogen in soil and on the efficiency of nitrogen utilization for biomass production and yield. However, knowledge about molecular responses to nitrogen fluctuations mainly derives from the study of model species. Nitric oxide (NO) has been proposed to be implicated in plant adaptation to environment, but its exact role in the response of plants to nutritional stress is still under evaluation. Recently a novel role for NO production and scavenging, thanks to the coordinate spatio-temporal expression of nitrate reductase and non-symbiotic hemoglobins, in the maize root response to nitrate, has been postulated. This control of NO homeostasis is preferentially accomplished by the cells of the root transition zone (TZ) which seems to represent the most nitrate responsive portion of maize root. The TZ is already known to function as a sensory center able to gather information from the external environment and to re-elaborate them in an adequate response. These results indicate that it could play a central role also for nitrate sensing by roots. A lot of work is still needed to identify and characterize other upstream and downstream signals involved in the “nitrate-NO” pathway, leading to root architecture adjustments and finally to stress adaptation.
Tocolysis for Women With Early Spontaneous Preterm Labor and Advanced Cervical Dilation

OBJECTIVE: To characterize tocolytic use and examine perinatal outcomes among women presenting very preterm with spontaneous labor and cervical dilation 4 cm or greater. METHODS: This was a retrospective cohort study. Data from January 2000 to June 2011 in a single health care system were reviewed. Women with singleton, nonanomalous fetuses and preterm labor with intact membranes between 23 and 32 weeks of gestation who had cervical dilation 4 cm or greater and less than 8 cm at admission were included. Women receiving one or more tocolytics (magnesium sulfate, indomethacin, or nifedipine) were compared with those who did not receive tocolysis. The primary outcome was composite major neonatal morbidity. RESULTS: Two hundred ninety-seven women were included; 233 (78.5%) received at least one tocolytic. Women receiving tocolysis were slightly less dilated (median 5 compared with 6 cm, P<.001) at presentation and were more likely to receive at least a partial course of corticosteroids (88.4% compared with 56.3%, P<.001). Initial composite severe neonatal morbidity rates were similar (41.6% compared with 43.8%, P=.761) regardless of tocolytic administration. Those receiving tocolysis were significantly more likely to be pregnant at least 48 hours after admission (23.6% compared with 7.8%, P=.005), but a similar proportion delivered within 7 days of admission (94.8% compared with 95.3%, P>.99), and delivery gestational ages were similar (28.9 compared with 29.2 weeks, P=.408). The incidence of chorioamnionitis and postpartum endometritis was similar between groups. CONCLUSION: The majority of women presenting very preterm with advanced cervical dilation received tocolysis. Although tocolysis administration increased the likelihood of achieving at least 48 hours of latency, initial neonatal outcomes were similar. LEVEL OF EVIDENCE: II
Cognitive behavioral therapy and predictors of weight loss in bariatric surgery patients

Purpose of review Bariatric surgery is the most effective treatment for morbid obesity. However, 20–30% of patients undergoing bariatric surgery experience premature weight stabilization or weight regain postoperatively. We report on the recent literature of predictors of weight loss and the efficacy of cognitive behavioral therapy (CBT) in bariatric patients. Recent findings Preoperative disordered eating behaviors do not appear to be significantly predictive of postoperative weight loss. Postoperative disordered eating behaviors, eating disorders, and depressive symptoms have been found to be associated with less optimal weight loss results. Recent studies show that CBT can contribute in reducing disordered eating behaviors and depressive symptoms. Some studies also show that pre and postoperative CBT interventions can promote weight loss. New applications of CBT such as by telephone, internet, or virtual reality might contribute to more accessible and low-cost treatments for the large group of bariatric patients worldwide. Summary CBT seems to be effective in reducing risk factors for weight regain after bariatric surgery, such as disordered eating behavior and depression. Controlled studies with long-term follow-up and larger sample sizes are needed to investigate the long-term effect of CBT interventions on weight loss results and psychological well-being.
Clinical evaluation of a low-shrinkage composite in posterior restorations: one-year results.

OBJECTIVES The aim of this study was to compare the one-year clinical performance of three restorative systems, which included a novel low-shrinkage composite and two bonding strategies. MATERIALS AND METHODS Twenty-five patients received three Class I (occlusal) or Class II restorations performed with one of three restorative systems: Filtek Silorane Restorative System (FS); Adper Scotchbond 1 XT, a two-step etch-and-rinse adhesive, with Filtek Z250 (XT); and Adper Scotchbond SE, a two-step self-etch adhesive, with Filtek Z250 (SE). All materials were applied following the manufacturer's instructions. Two independent observers evaluated the restorations at baseline, after six months, and after one year, according to the United States Public Health System modified criteria. The Kruskal-Wallis test and the Mann-Whitney U-test were computed to compare the behavior of the restorative systems; Friedman and Wilcoxon tests were used to analyze the intrasystem data (α=0.05). RESULTS All restorations were evaluated at one year. FS and XT performed statistically similarly at one year, but marginal staining for SE was statistically worse. Intrasystem comparisons between baseline and one year also showed deterioration of marginal staining for SE, while a deterioration of the marginal adaptation was recorded for both SE and FS. XT was the only system for which there was no statistical change of the parameters measured in this study. CONCLUSIONS Both restorative systems using self-etch adhesives showed a tendency to degradation of marginal adaptation after one year of clinical use, compared to baseline values. Although the clinical performance of FS was deemed acceptable after one year, this study did not find any advantage of the silorane-based composite over the methacrylate-based composite. The low-shrinkage associated with FS may not be a determinant factor for clinical success.
[The value of Tc99m-DMSA renal scintigraphy in evaluation of severity of parenchymal lesions in children with acute urinary tract infection].

INTRODUCTION Most authors would agree that renal parenchymal defects (scars, hypoplasia, dysplasia) in children are a major risk factor for chronic renal failure, and for development of systemic hypertension in later years. The pathophysiologic changes in acute pyelonephritis include tubulointerstitial inflammation/pus with impairment of the renal microcirculation due to compression of the glomeruli, small peritubular capillaries and vasa recta by interstitial edema. The resulting ischemia has been postulated as one of the mechanisms for the decreased accumulation of DMSA in the areas of pyelonephritis. DMSA scanning has a sensitivity of up to 99%, and specificity of up to 91% for the detection of acute pyelonephritis. AIM OF THE STUDY The aim of the study was to investigate the value of Tc99m-DMSA scan in children with acute urinary tract infection, to estimate the degree of parenchymal changes, and to assess the relationship with vesicoureteral reflux. PATIENTS We reviewed 116 infants aged 0-15 years, 100 (86.2%) female and 16 (13.8%) male, who were hospitalized for urinary tract infection during a 5-year period (1996-2000). The mean age at diagnosis was 3.7 years. RESULTS Escherichia colli was isolated in 52 (44.8%) urine cultures. All patients underwent ultrasonography, which was normal in 57 (49.1%) infants. Tc99m-DMSA was performed after two weeks of therapy. The renal parenchymal pathology was defined as a focal or multifocal defect of low degree in 33 (28.4%), and of high degree in 35 (30%) children. Multifocal defects were mostly found in patients aged < 3 years, and focal lesions in those aged > 3 years. Renal scars were detected in 41 (35.3%) infants with first urinary tract infection. CONCLUSION We recommend that ultrasound, DMSA and radionuclide cystouretherogram be routinely performed in case of first urinary tract infection in infants aged < 1 year, and voiding cystourethrogram with US and DMSA in those aged > 1 year.