Miracle-dz/UniFAR-FTUs huggingface dataset:
Thymosin‐α1 regulates MHC class I expression in FRTL‐5 cells at transcriptional level

In this study we examined the effect of the synthetic peptide thymosin‐α1 (Tα1) on MHC class I expression in FRTL‐5 cells. Treatment with Tα1 increased expression of MHC class I surface molecules and mRNA, which reached its peak (153 ± 8 % of the control value) after 12 h. Chloramphenicol acetyltransferase (CAT) analysis, following transfection with a plasmid containing the regulatory sequence of MHC class I (or its deletion derivatives) with the CAT reporter gene, and electrophoretic mobility shift assay experiments demonstrated that the action of Tα1 was at the transcriptional level, and its mechanism of action is likely due to increased binding between the complex p50 / fra‐2 and the enhancer A sequence of the 5' flanking region of a swine class I gene (PD1). An increase in the expression of MHC class I surface molecules was also observed by flow cytometry in murine and human tumor cell lines and in primary cultures of human macrophages. This study shows for the first time an effect of Tα1 on the regulation of gene expression at the molecular level, and may further contribute to explaining the results obtained using Tα1 in the control of infectious diseases and tumor growth.
Determinants of poor blood pressure control in urban hypertensives of central India.

OBJECTIVES To determine the factors responsible for poor blood pressure (BP) control among patients started on treatment for hypertension, with the hypothesis that patient non-compliance would be an important determinant. DESIGN Patients attending the Cardiology Clinic of the Government Medical College, Nagpur with hypertension for the first time were followed for 3 months and labelled as uncontrolled, if at end of this time the mean of two measures of diastolic blood pressure (DBP) was > 95 mm Hg, despite apparently adequate anti-hypertensive drugs. STUDY FACTORS Compliance (measured by pill count), life stress (measured by life event score), smoking and alcohol intake and demographic variables (measured by an interviewer-administered questionnaire), and body mass index (BMI). RESULTS Of 156 subjects recruited, 139 (89%) completed follow-up of 3 months, of whom 45 (32%) had uncontrolled hypertension (DBP > 95 mm Hg) at the end of follow-up. There was no statistically significant difference in the baseline characteristics of subjects who completed follow-up as compared with those lost to follow-up. The mean age of the patients was 55 years and male to female ratio was 1.5:1. Sixty-one per cent of the uncontrolled hypertensives were non-compliant by pill count (taking < 80% of drugs) as compared to 21% of the controlled hypertensives (odds ratio, OR = 6.1, 95% Cl = 3.9-12.6; P < 0.0001). There was no statistically significant difference in the mean age, mean BMI, sex distribution, alcohol intake, cigarette smoking rates, educational level, occupational or marital status between controlled and uncontrolled hypertensives. The median life event score (LES) was significantly higher in uncontrolled than in controlled hypertensives 4 vs 1.5 (P < 0.00001). Multiple logistic regression analysis found non-compliance and LES to be statistically significant independent predictors of uncontrolled hypertension. CONCLUSION Patient non-compliance with drugs and life stress may help explain poor BP control in patients on treatment for hypertension in this setting.
Measurable lower bounds on concurrence

We derive measurable lower bounds on concurrence of arbitrary mixed states, for bothbipartite and multipartite cases. First, we construct measurable lower bonds on thepurely algebraic bounds of concurrence [F. Mintert et al. (2004), Phys. Rev. lett. , 92,167902]. Then, using the fact that the sum of the square of the algebraic bounds is alower bound of the squared concurrence, we sum over our measurable bounds to achievea measurable lower bound on concurrence. With two typical examples, we show that ourmethod can detect more entangled states and also can give sharper lower bonds thanthe similar ones.
Analysis of three clustered polygalacturonase genes in Erwinia chrysanthemi 3937 revealed an anti‐repressor function for the PecS regulator

Erwinia chrysanthemi 3937 secretes an arsenal of pectinolytic enzymes including several pectate lyases encoded by the pel genes. We characterized a novel cluster of pectinolytic genes consisting of the three adjacent genes pehV, pehW and pehX, whose products have polygalacturonase activity. The high similarity between the three genes suggests that they result from duplication of an ancestral gene. The transcription of pehV, pehW and pehX is dependent on several environmental conditions. They are induced by pectin catabolic products and this induction results from inactivation of the KdgR repressor which controls almost all the steps of pectin catabolism. The presence of calcium ions strongly reduced the transcription of the three peh genes. Their expression was also affected by growth phase, osmolarity, oxygen limitation and nitrogen starvation. In addition, the pehX transcription is affected by catabolite repression and controlled by the activator protein CRP. PecS, which was initially isolated as a repressor of virulence factors, acts as an activator of the peh transcription. We showed that the three regulators KdgR, PecS and CRP act by direct interaction with the promoter regions of the peh genes. Analysis of simultaneous binding of KdgR, PecS, CRP and RNA polymerase indicated that the activator effect of PecS results from a competition between PecS and KdgR for the occupation of overlapping binding sites. Thus, to activate peh transcription, PecS behaves as an anti‐repressor against KdgR.
Probing the In Vivo Dynamics of Type I Protein Secretion Complex Association through Sensitivity to Detergents

ABSTRACT The Serratia marcescens hemophore is secreted by a type I secretion system consisting of three proteins: a membrane ABC protein, an adaptor protein, and the TolC-like outer membrane protein. Assembly of these proteins is induced by substrate binding to the ABC protein. Here we show that a hemophore mutant lacking the last 14 C-terminal amino acids is not secreted but rather interacts with the ABC protein and promotes a stable multiprotein complex. Strains expressing the transporter and the mutant protein are sensitive to detergents (sodium dodecyl sulfate [SDS]). TolC is trapped in the transporter jammed by the truncated substrate and therefore is not present at sufficient concentrations to allow the efflux pumps to expel detergents. Using an SDS sensitivity assay, we showed that the hemophore interacts with the ABC protein via two nonoverlapping sites. We also demonstrated that the C-terminal peptide, which functions as an intramolecular signal sequence in the complete substrate, may also have intermolecular activity and triggers complex dissociation in vivo when it is provided as a distinct peptide. The SDS sensitivity test on plates enables workers to study type I secretion protein association and dissociation independent of the secretion process itself.
Prognostic features of asymptomatic multiple myeloma

Approximately 20% of patients with multiple myeloma are recognized by chance without significant symptoms. In order to prevent morbidity with timely therapy, reliable criteria are needed that distinguish those likely to show early or late disease progression. Multiple clinical features were assessed in 101 consecutive, asymptomatic and previously untreated patients. Patients with one or more lytic bone lesions were excluded because this feature had been found previously to be associated with early progression. Multivariate analysis indicated that only serum myeloma globulin >30 g/l, IgA protein type, and Bence Jones protein excretion >50 mg/d remained as significant independent variables. The presence of two or more of these features signified high‐risk disease with early progression (median 17 months) whereas the absence of any adverse variable was associated with prolonged stability (median 95 months) (P <0.01. Magnetic resonance (MR) imaging of the spine was useful only in patients with one adverse feature and an intermediate time to progression (median 39 months). An abnormal pattern (40% of patients) helped to distinguish patients with an imminent complication from those with more stable disease. Because a serious complication (fracture, hypercalcaemia) occurred in 35% of patients with early disease progression, chemotherapy seems justified for selected patients with asymptomatic disease at diagnosis. The remaining patients were at such low risk for progression (median 6 years) that they may be followed safely at long intervals without treatment.
Gating currents from neuronal KV7.4 Channels: General features and correlation with the ionic conductance

The KV7 (KCNQ) subfamily of voltage-gated K+ channels consists of five members (KV7.1- KV7.5) giving rise to non-inactivating, and slowly activating/deactivating currents mainly expressed in cardiac (KV7.1) and neuronal (KV7.2- KV7.5) tissue. In the present study, using the cut-open oocyte voltage clamp, we studied the relation of the ionic currents from homomeric neuronal Kv7 channels (KV7.2-KV7.5) with the gating currents recorded after K+ conductance blockade from the same channels. Increasing the recording temperature from 18{degree sign}C to 28{degree sign}C accelerated activation/deactivation kinetics of the ionic currents in all homomeric KV7 channels (activation Q10s at 0 mV were 3.8, 4.1, 8.3, and 2.8 for Kv7.2, Kv7.3, Kv7.4 and Kv7.5 channels, respectively), without large changes in currents voltage-dependence; moreover, at 28{degree sign}C, ionic currents carried by KV7.4 channels also showed a significant increase in their maximal value. Gating currents were only resolved in KV7.4 and KV7.5 channels; the size of the ON gating charges at +40 mV was 1.34 ± 0.34 nC for KV7.4, and 0.79 ± 0.20 nC for KV7.5. At 28{degree sign}C, KV7.4 gating currents had the following salient properties: 1) similar time integral of QON and QOFF, indicating no charge immobilization; 2) a left-shift in the V1/2 of the QON/V when compared to the G/V (≈ 50 mV in the presence of 2 mM extracellular Ba2+); 3) a QON decay faster than ionic current activation; and 4) a rising phase in the OFF gating charge after depolarizations larger than 0 mV. These observations suggest that, in KV7.4 channels, VSD movement is followed by a slow and/or low bearing charge step linking to pore opening, a result which may help to clarify the molecular consequence of disease-causing mutations and drugs affecting channel gating.
Effects of recombinant human erythropoietin in normal humans

This review describes some of the physiological effects of recombinant human erythropoietin (EPO) in healthy humans. At the blood level EPO increases the arterial O2 content not only by increasing red blood cell volume, but also by an equally important decrease in plasma volume. Well before that, EPO causes a prompt decrease in plasma levels of renin and aldosterone. Renal clearance studies suggest that EPO decreases renal proximal tubular reabsorption rate leading to activation of the tubuloglomerular feedback mechanism and a fall in glomerular filtration rate. Thus, treatment with EPO may result in suppression of endogenous EPO production through a decrease in intrarenal oxygen consumption. EPO elevates the arterial blood pressure even in healthy subjects. The receptor for EPO is present in many tissues. However, the functional effects of EPO in the skeletal muscle seem limited, and although it has been speculated that non‐erythropoietic effects of EPO (angiogenesis, shift in muscle fibre types, cognitive effects) may be responsible for the increase in exercise performance, this has not been confirmed. EPO‐induced haemodynamic effects call for careful monitoring during the administration period. The metabolic, hormonal and renal effects of EPO do not seem to range beyond physiologically acceptable limits and are reversible. Taken together, EPO seems safe to use for experimental purposes in healthy volunteers.
The Epidemiology of Diabetic Foot Problems

Diabetic foot ulcers are common and estimated to affect 15% of all diabetic individuals during their lifetimes. The majority of foot ulcers are treated in outpatient settings where surveillance is limited. Hospital discharge data from select countries indicated that 6-20 % of all diabetic individuals hospitalized had a lower extremity ulcer condition.2•3 To illustrate trends in inpatient hospitalization, US National Hospital Discharge Survey Data (NHDS) data for seven foot ulcer related conditions from 1983 to 1990 will be used. These data revealed an overall increase of approximately 50% in the age standardized proportion of hospital discharges listing diabetes and lower extremity ulcers during this interval.2 The highest rates were observed in patients ages 45-64 years while the lowest rates documented were in patients ages 044 years. The age-standardized proportion of hospital discharges listing diabetes and lower extremity ulcers showed that diabetic foot ulcer rates were consistently
HIV-Specific CD8+ T Cells from Elite Controllers Are Primed for Survival

ABSTRACT HIV-specific cytotoxic T lymphocytes (CTL) are preferentially primed for apoptosis, and this may represent a viral escape mechanism. We hypothesized that HIV-infected individuals that control virus to undetectable levels without antiretroviral therapy (ART) (elite controllers [EC]) have the capacity to upregulate survival factors that allow them to resist apoptosis. To address this, we performed cross-sectional and longitudinal analysis of proapoptotic (cleaved caspase-3) and antiapoptotic (Bcl-2) markers of cytomegalovirus (CMV) and HIV-specific CD8 T cells in a cohort of HIV-infected subjects with various degrees of viral control on and off ART. We demonstrated that HIV-specific CTL from EC are more resistant to apoptosis than those with pharmacologic control (successfully treated patients [ST]), despite similar in vivo conditions. Longitudinal analysis of chronically infected persons starting ART revealed that the frequency of HIV-specific T cells prone to death decreased, suggesting that this phenotype is partially reversible even though it never achieves the levels present in EC. Elucidating the apoptotic factors contributing to the survival of CTL in EC is paramount to our development of effective HIV-1 vaccines. Furthermore, a better understanding of cellular markers that can be utilized to predict response durability in disease- or vaccine-elicited responses will advance the field.
Performance of GaAs JFET at a cryogenic temperature for application to readout circuit of high-impedance detectors

A GaAs junction field effect transistor (JFET) is a promising candidate for the cryogenic electronics of high-impedance sensitive photoconductors because of its low-noise at low frequencies. This GaAs JFET has advantages compared with other type of FETs, such as no kink phenomena or hysteresis in its current-voltage (I-V) characteristics, small gate leakage currents, and minute capacitance. We report on the noise spectra and leakage current of a SONY n-type GaAs FET in a high-impedance configuration where the gate terminal was surrounded by high-impedance devices at a cryogenic temperature, i.e., 4.2 K. In the high-impedance configuration, we obtained a low noise level and low leakage current of 0.5 /spl mu/V/Hz/sup 1/2/ at 1 Hz and 4.6/spl times/10/sup -19/ A. This result implies that the GaAs JFET is suitable for cryogenic readout electronics. We also discuss the source of the random telegraph signal and the 1/f noise in the GaAs JFET at cryogenic temperatures.
Load reduction in wind turbines with smart rotors using trial varying iterative learning control law

Control of aerodynamic loads is a crucial issue in keeping wind energy economically competitive with traditional energy sources. This paper continues the investigation of the use of Iterative Learning Control (ILC) for load control in wind turbines with smart devices on rotor blades. A relatively simple computational fluid dynamics model is used to simulate the flow past an airfoil. Assuming no actuator delay, fluctuations in load due to periodic disturbances can be almost completely eliminated by a simple ILC control scheme. In application, however, delay due to the actuators will arise and could have a negative effect on real-time performance and influence the desired attenuation. This paper develops a novel method of using trial varying ILC to improve aerodynamic load performance in the presence of actuator dynamics. The results of a simulation based assessment of the new control system are also given and areas for possible future research discussed.
Comparison of brain gray and white matter macromolecule resonances at 3 and 7 Tesla

In proton MR spectra of the human brain, relatively broad macromolecule (MM) resonances underlie the narrower signals from metabolites. The purpose of this study was to quantify the MM profile in healthy human brain at 3T and 7T, both in gray matter (anterior cingulate cortex [ACC]) and white matter (centrum semiovale [CSO]).
Cochlear pathology of the circling mouse: a new mouse model of DFNB6

Conclusion. The circling mouse (cir/cir) has phenotypes which follow the pattern of neuroepithelial defects of deafness from 10 days after birth. The cir mouse is defective in Tmie gene, the function of which should be further elucidated. Objectives. We previously reported a recessive mutation of deafness called circling mice (cir/cir). The present study focused on investigating phenotypes and histological findings of the cochlea in circling mice with respect to age. Materials and methods. In order to analyze cochlear pathology over time, five different age groups of circling mice were examined (10, 18, 21, 35, and 90 days old). The organs of Corti and spiral ganglion neurons in basal and middle turns were evaluated. Results. The pathology of the organ of Corti followed the pattern of neuroepithelial defects. Hair cells in organs of Corti had degenerated in circling mice at 10 days old, in a time-dependent manner. Scanning electron microscopy (SEM) showed that stereociliary bundles were irregular in size and had shortened at 10 days, and that this degeneration was complete at 21 days. The number of spiral ganglion neurons significantly reduced with age. RT-PCR analysis indicated that the transmembrane inner ear gene (Tmie) was absent in various organs in circling mice.
Cardiovascular Effects of Psychotropic Drugs

Background Cardiovascular disease is the leading cause of death in the general population and accounts for approximately 30% of all deaths; some of these are due to fatal arrhythmias, especially ventricular fibrillation. In a psychiatric population the prevalence of cardiovascular disease is higher than in the general population because of a different lifestyle and greater frequency of risks factors such as smoking, obesity, and increased stress. The increased prevalence of sudden death in this patient population has given rise to the question of drug-induced cardiovascular and arrhythmic effects. This article reviews the principal classes of psychotropic medications and their effects on the heart. Methods The review is based on Medline, Pubmed, Cochrane, and literature searches of publications from the period 1984 to 2005. Conclusion It is important for practitioners to be familiar with the possible effects of psychotropic medications on the cardiovascular system, especially in the elderly and other patients with preexisting cardiac problems. Before starting treatment with a new psychotropic medication, a careful history and physical are mandatory, and baseline liver, lipid, and kidney profiles as well as chest radiographic and electrocardiographic findings should be noted.
Interest in rural clinical school is not enough: Participation is necessary to predict an ultimate rural practice location

OBJECTIVE Rural exposure during medical school is associated with increased rural work after graduation. How much of the increase in rural workforce by these graduates is due to pre-existing interest and plans to work rurally and how much is related to the extended clinical placement is not known. DESIGN This cohort study compared the employment location of medical graduates who professed no rural interest as undergraduates (negative control), with those who applied but did not participate in Rural Clinical School of Western Australia (RCSWA) (positive control), and those who applied and participated in RCSWA (participants). PARTICIPANTS All 1026 University of Western Australia students who had an opportunity to apply for a year-long rotation in RCSWA from 2004 to 2010, and who had subsequently graduated by the end of 2011, were included. MAIN OUTCOME MEASURE Graduates' principal workplace location (AHPRA, Feb 2014). RESULT The three groups differed significantly in their graduate work locations (χ2 = 39.2, P < 0.001). In multivariate analysis, only being of older age at graduation (OR 2.28 (95% CI 1.40, 3.72), P = 0.001), being from a rural background (OR 2.99 (95% CI 1.85, 4.85), P < 0.001), being a recipient of a Medical Rural Bonded Scholarship (OR 3.36 (95% CI 1.68, 6.73, P = 0.001) and actually participating in the RCSWA remained significantly related to rural work (OR 3.10 (95% CI 1.95, 4.93), P < 0.001). CONCLUSION After accounting for other factors relating to rural work, RCSWA graduates were three times more likely to work rurally than either control group. These data suggest that RCSWA has a significant independent effect on rural workforce.
Metabolic and toxicological considerations of the opioid replacement therapy and analgesic drugs: methadone and buprenorphine

Introduction: Methadone and buprenorphine are maintenance replacement therapies for opioid dependence; they are also used for pain management. Methadone and buprenorphine (to a lesser extent) have seen sharp increases in mortality associated with their use. They have distinct routes of metabolism (mostly cytochrome P450 dependent), and distinct pharmacologic activity of metabolites. As such, metabolism may play a role in differences in their toxicity. Areas covered: This article reviews peer-reviewed literature obtained from PubMed searches and literature referenced within. The review considers first an overview of drug use and mortality over the past decade. It then provides extensive detail on the in vitro and in vivo human metabolism of methadone and buprenorphine. Using both human and experimental animal studies it then presents the pharmacodynamic activity of parent drug and metabolites at the mu-opioid receptor, as P-glycoprotein substrates and plasma/brain concentration ratios, and activity at the hERG K+ channel. Lessons learned from drug interaction studies in humans are then examined in an attempt to bring together the combined information. Expert opinion: The use and misuse of these drugs contributes to the epidemic in opioid-associated mortalities. A better understanding of metabolism-, transport- and co-medication-induced changes will contribute to their safer use.