Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction with model membranes and pore formation by human stefin B – studying the native and prefibrillar states

Human stefin B, from the family of cystatins, is used as a model amyloidogenic protein in studies of the mechanism of amyloid fibril formation and related cytotoxicity. Interaction of the protein’s prefibrillar oligomers/aggregates with predominantly acidic phospholipid membranes is known to correlate with cellular toxicity. In the present study, we measured membrane interaction of the prefibrillar and native states for three variants: the Y31 isoform studied previously, the wild‐type protein and the G4R mutant; the latter is observed in progressive myoclonus epilepsy of type 1. In addition to using critical pressure and surface plasmon resonance, we assessed membrane permeabilization by calcein release and electrophysiological measurements. It was demonstrated for the first time that wild‐type stefin B and the Y31 isoform are able to form pores in planar lipid bilayers, whereas G4R destroys the bilayer by a non pore‐forming process. Similarities to other amyloidogenic proteins and the possible physiological implications of our findings are discussed.
Physical activity, mental stress, and short-term heart rate variability in patients with ischemic heart disease.

BACKGROUND Among the general population, mental stress seems to depress heart rate variability (HRV), and physical activity level seems to be positively associated with HRV. However, the extent to which these relationships exist among patients with ischemic heart disease is not clear. Therefore, this study investigated the association between level of physical activity and HRV among patients with ischemic heart disease during conditions of paced breathing and the Stroop Color-Word Conflict Test (Stroop). METHODS Forty-two patients with ischemic heart disease were assigned to groups based on their documented volume of aerobic activity: Low = 1.008-2.646 kJ/wk; Mod = 3.024-3.864 kJ/wk; and High = 4.284-7.560 kJ/wk. These groups did not differ in age, body mass index, or hostility as determined by the Minnesota Multiphasic Personality Inventory. Time and frequency domain measures of HRV were derived from electrocardiograph data obtained during 5 minutes of paced respiratory control and 5 minutes of performing the Stroop Test. RESULTS There was a main effect of activity level (P < 0.05) on the standard deviation of R-wave to R-wave intervals (SDNN), total spectral power, and high-frequency power such that these dependent variables were greater in the High group than in the Low or Mod group. Furthermore, there was a main effect of the test condition on SDNN and total power, both of which were lower during the Stroop Test as compared to paced respiratory control. CONCLUSIONS The results indicate that, among patients with ischemic heart disease, a high level of physical activity is associated with higher HRV, but is not related to stress reactivity as measured by HRV.
Phagocytosis of apoptotic inflammatory cells downregulates microglial chemoattractive function and migration of encephalitogenic T cells

Apoptosis of autoaggressive T cells in the central nervous system (CNS) and subsequent phagocytosis by microglia is probably crucial in the rapid resolution of the inflammatory infiltrate in T cell mediated neuroinflammatory diseases. In addition to mere clearance, phagocytosis of apoptotic leukocytes results in the downregulation of different microglial immune functions. Chemoattractive functions of Lewis rat microglia and secretion of chemokines and matrix‐metalloproteinases (MMPs) were investigated after phagocytosis of apoptotic T cells in vitro. In a modified Boyden chamber assay migration of encephalitogenic T cells toward LPS‐stimulated microglial supernatants after phagocytosis of apoptotic thymocytes was reduced by 24.9% in comparison to interaction with viable target cells (P < 0.001). Phagocytosis of apoptotic cells downregulated CC‐chemokine ligand (CCL)‐5‐secretion by LPS‐stimulated microglia by 66.2% (P < 0.001), whereas there was only a trend toward decreased CCL2‐secretion. As determined by gelatinase‐zymography, secretion of MMP‐9 by microglia was decreased after phagocytosis of apoptotic cells, whereas MMP‐2 secretion was not altered. These mechanisms may reduce further recruitment of pathogenic inflammatory cells into the CNS‐lesion and thus contribute to the active resolution of the inflammatory infiltrate and termination of the autoimmune attack. © 2006 Wiley‐Liss, Inc.
Effectiveness of platelets rich plasma versus corticosteroids in lateral epicondylitis.

OBJECTIVE To compare the treatment modalities of lateral epicondylitis in terms of pain relief. METHODS The randomised controlled study was conducted at Hayatabad Medical Complex, Peshawar, Pakistan, from April 2013 to March 2014, and comprised cases of lateral epicondylitis. The patients were selected through consecutive sampling from the outpatient department and were randomly allocated to two equal groups; group A receiving corticosteroid injections, and group B receiving injection of platelet-rich plasma. The patients were followed up for three weeks to determine the effectiveness of intervention. RESULTS The 102 patients in the study were divided into two groups of 51(50%) each. The over mean age was 33.9±10.3 years. Mean age of patients in the corticosteroid group was 34.2±10.2 years and in the other group it was 33.6±10.5 years. Mean baseline visual analogue score in group A were 6.5±1.2 and in group B it was 6.7±1.4. In group A, 74.5% of patients presented in moderate pain category and 25.5% presented in severe pain category. In group B, 70.6% presented in moderate with 29.4% presented in severe pain category. On follow-up, the mean pain score in group A was 4.0±2.6 and in group B it was 3.5±2.61. Group A showed effectiveness in 52.9% patients and group B showed effectiveness in 82.3% (p=0.001). CONCLUSIONS PRP is an effective alternate to corticosteroid in the treatment of lateral epicondylitis (tennis elbow).
Cannabinoid receptor 1 mediates palmitic acid‐induced apoptosis via endoplasmic reticulum stress in human renal proximal tubular cells

The endocannabinoid system (ECS) is activated at the onset of obesity and diverse metabolic diseases. Endocannabinoids mediate their physiological and behavioral effects by activating specific cannabinoid receptors, mainly cannabinoid receptor 1 (CB1R). Diabetic nephropathy (DN) is induced by hyperlipidemia, and renal proximal tubule cells are an important site for the onset of DN. However, the pathophysiology of CB1R, especially in the hyperlipidemia of DN, has not been elucidated. Therefore, we examined the effect of palmitic acid (PA) on CB1R expression and its related signal pathways in human renal proximal tubular cells (HK‐2 cells). PA significantly increased CB1R mRNA and protein levels and induced CB1R internalization. PA‐induced activation of CB1R is prevented by the treatment of AACOCF3 (a cPLA2 inhibitor), indomethacin and NS398 (a COX 2 inhibitors). Indeed, PA increased cPLA2, and COX‐2 but not COX‐1. We also investigated whether the PA‐induced activation of CB1R is linked to apoptosis. As a result, AM251 (a CB1R antagonist) attenuated PA‐mediated apoptosis in a concentration‐dependent manner. Furthermore, PA decreased GRP78 expression and induced increases in the endoplasmic reticulum (ER) stress signaling pathways p‐PERK, p‐eIF2α, p‐ATF4, and CHOP, which were blocked by AM251 treatment. Moreover, PA increased the Bax/Bcl‐2 ratio, cleaved PARP, and caspase‐3 levels. The PA‐induced apoptotic effects were decreased with CB1R‐specific antagonist (AM251) treatment and CB1 si‐RNA transfection. In conclusion, PA induced apoptosis through ER stress via CB1R expression in human proximal tubule cells. Our results provide evidence that CB1R blockade may be a potential anti‐diabetic therapy for the treatment of DN. J. Cell. Physiol. 225: 654–663, 2010. © 2010 Wiley‐Liss, Inc.
Copeptin is not a useful biomarker for small-for-gestational-age: a case control study

Abstract Objective. To investigate copeptin as a biomarker for small-for-gestational-age. Methods. We conducted a nested case-control study on maternal copeptin levels measured in gestational week 12 and 19 and risk of small-for-gestational age. Cases were defined as pregnant women who delivered a small-for-gestational-age infant. Small-for-gestational age was defined as a birth weight − 22% or less than expected according to gestational age (n = 39). Controls were pregnant women who delivered a normal-weight infant (n = 119). The copeptin ultrasensitive Kryptor kit (BRAHMS) was used to determine copeptin in maternal serum. We established reference ranges for copeptin by 95% prediction intervals with 90% confidence intervals. Paired and unpaired t-tests were performed to test the null-hypothesis of no difference in copeptin levels within and between the groups. Results. The reference intervals for copeptin in normal pregnancies were 1.24–5.51 pmol/L (90% confidence intervals on upper and lower limit were 1.13–1.37 and 5.00–6.08 pmol/L) at gestational week 12, and 1.30–5.09 pmol/L (90% confidence intervals were 1.19–1.42 and 4.65–5.57 pmol/L) at gestational week 19. Copeptin levels decreased from week 12–19 in cases (p = 0.02), whereas no change was observed in controls (p = 0.61). We found no difference in copeptin levels in cases compared to controls in gestational week 12 (p = 0.10) and week 19 (p = 0.81). Conclusion. The present study could not demonstrate copeptin as a novel biomarker for small-for-gestational-age.
Simultaneous Active and Reactive Power Control of Superconducting Magnet Energy Storage Using GTO Converter

By using GTO's (Gate Turn-Off Thyristor) in place of ordinary thyristors in a conventional six pulse Greatz bridge converter, forced commutation is possible, so in the usage of ac-dc power conversion the reactive power of not only lagging but also leading phase can be absorbed. This feature enables superconducting magnet energy storage (SMES) to control reactive power in the wide range between lagging and leading phases. By virtue of this control ability , SMES will be applicable for a power system stabilyzer. A GTO converter which mainly consists of six GTO's was developed and tested. In this GTO converter, the energy stored in leakage inductances of the transformer is handled by voltage clipper circuit. Then, by using two sets of these GTO converters, we carried out some experiments of simultaneous active and reactive power control of SMES. The experiments on the developed control system were successfully performed and the ability of controlling reactive power in the wide range between lagging phase and leading phase was verified.
Identification of UreR binding sites in the Enterobacteriaceae plasmid‐encoded and Proteus mirabilis urease gene operons

The closely related Proteus mirabilis and Enterobacteriaceae plasmid‐encoded urease genes are positively regulated by the AraC‐like transcriptional activator UreR. In the presence of the effector molecule urea, UreR promotes transcription of ureD, the initial gene in the urease operon, and increases transcription of the divergently transcribed ureR. Here, we identify UreR‐specific binding sites in the ureRp–ureDp intergenic regions. Recombinant UreR (rUreR) was expressed and purified, and gel shift and DNase I protection assays were performed with this protein. These analyses indicated that there are two distinct rUreR binding sites in both the plasmid‐encoded and P. mirabilis ureRp–ureDp intergenic regions. A consensus binding site of TA/GT/CA/TT/GC/TTA/TT/AATTG was predicted from the DNase I protection assays. Although rUreR bound to the specific DNA binding site in both the presence and the absence of urea, the dissociation rate constant k–1 of the rUreR–DNA complex interaction was measurably different when urea was present. In the absence of urea, the dissociation of the protein–DNA complexes, for both ureRp and ureDp, was complete at the earliest time point, and it was not possible to determine a rate. In the presence of urea, dissociation was measurable with a k–1 for the rUreR–ureRp interaction of 1.2 ± 0.2 × 10−2 s−1 and a k–1 for the rUreR–ureDp interaction of 2.6 ± 0.1 × 10−3 s−1. This corresponds to a half‐life of the ureRp–rUreR interaction of 58 s, and a half‐life of the ureDp–rUreR interaction of 4 min 26 s. A model describing a potential role for urea in the activation of these promoters is proposed.
Ergodic system capacity of mobile MIMO systems using adaptive modulation

In this paper the performance of multiple-input multiple-output (MIMO) system in the UTRAN Long Term Evolution (LTE) standard is evaluated by means of ergodic system capacity in low (3 km/h), medium (30 km/h) and high (120 km/h) mobility scenarios. The impact of adaptive modulation as well as Hybrid ARQ (HARQ) with Chase Combining to the distribution of effective SINR is established analytically and validated by simulations. A model for ergodic system capacity employing adaptive modulation and HARQ is developed. The simulation results show that adaptive modulation combined with HARQ increases the MIMO system performance significantly especially in low mobility case, and smaller reduction of rate is experienced in high mobility scenarios.
A weekly regimen with dose escalation of doxorubicin for patients with advanced Hodgkin's lymphoma: Results of a phase II study of the Groupe d'Études des Lymphomes de l'Adulte (GELA)

This multicenter phase II study assessed the feasibility and efficacy of a weekly chemotherapy regimen with a moderately escalated dose of doxorubicin administered over 16 weeks, followed by radiation therapy (RT) to bulky sites. From July 1996 to February 1998, 44 untreated patients with stage IIIB-IV Hodgkin's lymphoma (HL), and 0 – 2 risk factors described by the Memorial Sloan-Kettering Cancer Center, were treated. Chemotherapy was a combination of increased-dose doxorubicin with conventional doses of cyclophosphamide, vinblastine, prednisone, vindesine, bleomycin, and etoposide. Patients received four cycles of the weekly regimen for 16 weeks. Forty-one patients received the planned four cycles of chemotherapy, and RT was delivered to 36 patients. The incidence of WHO grade 3 – 4 neutropenia was 90%. A total of 39 patients achieved a complete remission (88.6%). The median follow-up was 95 months. The 7-years freedom from treatment failure and overall survival estimates were 57% (95% confidence interval (CI), 41% – 70%), and 93% (95% CI, 80 – 98%), respectively. The relapse rate was related to the short duration of chemotherapy, and the failure to prevent relapses with consolidation RT. In this study population the 16-week regimen and RT to bulky sites were not sufficient for disease control.
Activity breakdowns in QuickTime Virtual Reality environments

Recent research into virtual environments has identified difficulties that users have in navigating and searching for objects within a QuickTime Virtual Reality (QTVR) environment. Through the use of activity theory, the location and size of QTVR hotspots were identified as causing a breakdown between what the user expected to happen and what actually happened. This subsequently caused a focus shift from within the environment, out to the interface tool in order to try and overcome this breakdown. These breakdowns were the result of the environment design process. Careful planning of the environment is needed to greatly reduce these breakdowns.
Ribavirin therapy inhibits viral replication on patients with chronic hepatitis e virus infection.

BACKGROUND & AIMS Hepatitis E virus (HEV) infection can evolve to chronic hepatitis in immunocompromised patients. Pegylated α-interferon can effectively treat chronic HEV infection after liver transplantation but is contraindicated for kidney transplantation. We assessed the antiviral effect of ribavirin monotherapy in patients with chronic HEV infection following kidney transplantation. METHODS In a pilot study performed at Toulouse University Hospital, 6 patients that received kidney transplants who were positive for HEV RNA (infected with HEV for 36.5 months; [range, 11-46 months]) were given ribavirin monotherapy for 3 months. Ribavirin was given at 600-800 mg/day in 2 separate doses, based on the patient's ability to clear creatinine. RESULTS Median serum concentration of HEV RNA at baseline was 5.77 log copies/mL (range, 4.35-7.35 log copies/mL). Three months after ribavirin therapy commenced, HEV RNA was undetectable in serum samples from all patients. A sustained virologic response was observed in 4 patients; the other 2 patients relapsed at 1 and 2 months after ribavirin therapy ended. At the end of the study, all patients had normal levels of alanine and aspartate aminotransferase. Anemia was the main side effect caused by ribavirin therapy. CONCLUSIONS Ribavirin monotherapy inhibits the replication of HEV in vivo and might induce a sustained virological response in patients with chronic HEV infections. Further studies are required to determine the optimal duration of ribavirin therapy.
Alloimmune Responses and Atherosclerotic Disease After Kidney Transplantation

Background Chronic exposure to exogenous antigens causes accumulation of proinflammatory CD57+CD28− hyperactivated CD8+ T cells that may promote atherosclerosis. We hypothesized that persistent alloimmune responses may induce immune activation and contribute to posttransplant atherosclerosis. Methods This hypothesis was tested in a single-center cohort of 577 kidney transplant patients. Propensity score analysis was performed to address potential confounding variables by indication. Immune exhaustion was studied in subcohort of 103 patients. Results Five hundred seventy-seven consecutive renal transplant recipients were included. Seventy-seven atherosclerotic events (AE) (12.3%) occurred during a mean follow-up of 7 years. The cumulative incidence of AE increased with the number of human leukocyte antigen (HLA) mismatches (18%, 10%, and 5% in patients with 5–6, 3–4, and 0–2 mismatches, respectively; P=0.012). Human leukocyte antigen mismatch number (hazards ratio, 1.35; 95% confidence interval, 1.10–1.66, for each supplementary mismatch; P=0.005) was an independent risk factor for AE. In the propensity score match analysis, having received a well-matched kidney conferred a reduced risk of AE (hazards ratio, 0.22; 95% confidence interval, 0.05–0.95; P=0.044). We observed a significant correlation between HLA mismatch numbers and circulating CD57+CD28− CD8+ T cells (R=0.31; P=0.017). These CD8+ T cells were more frequent in patients with more HLA mismatches (P<0.0001). Conclusion Overall, our results suggest that chronic allogeneic stimulation participates to accelerated atherosclerosis observed after transplantation.
Mitotic Exit Control of the Saccharomyces cerevisiae Ndr/LATS Kinase Cbk1 Regulates Daughter Cell Separation after Cytokinesis

ABSTRACT Saccharomyces cerevisiae cell division ends with destruction of a septum deposited during cytokinesis; this must occur only after the structure's construction is complete. Genes involved in septum destruction are induced by the transcription factor Ace2, which is activated by the kinase Cbk1, an Ndr/LATS-related protein that functions in a system related to metazoan hippo pathways. Phosphorylation of a conserved hydrophobic motif (HM) site regulates Cbk1; at peak levels in late mitosis we found that approximately 3% of Cbk1 carries this modification. HM site phosphorylation prior to mitotic exit occurs in response to activation of the FEAR (Cdc fourteen early anaphase release) pathway. However, HM site phosphorylation is not sufficient for Cbk1 to act on Ace2: the kinase is also negatively regulated prior to cytokinesis, likely by cyclin-dependent kinase (CDK) phosphorylation. Cbk1 cannot phosphorylate Ace2 until after mitotic exit network (MEN)-initiated release of the phosphatase Cdc14. Treatment of Cbk1 with Cdc14 in vitro does not increase its intrinsic enzymatic activity, but Cdc14 is required for Cbk1 function in vivo. Thus, we propose that Cdc14 coordinates cell separation with mitotic exit via FEAR-initiated phosphorylation of the Cbk1 HM site and MEN-activated reversal of mitotic CDK phosphorylations that block both Cbk1 and Ace2 function.
A comparative study of saliency analysis and genetic algorithm for feature selection in support vector machines

Recently, support vector machine (SVM) has been receiving increasing attention in the field of regression estimation due to its remarkable characteristics such as good generalization performance, the absence of local minima and sparse representation of the solution. However, within the SVMs framework, there are very few established approaches for identifying important features. Selecting significant features from all candidate features is the first step in regression estimation, and this procedure can improve the network performance, reduce the network complexity, and speed up the training of the network. This paper investigates the use of saliency analysis (SA) and genetic algorithm (GA) in SVMs for selecting important features in the context of regression estimation. The SA measures the importance of features by evaluating the sensitivity of the network output with respect to the feature input. The derivation of the sensitivity of the network output to the feature input in terms of the partial derivative in SVMs is presented, and a systematic approach to remove irrelevant features based on the sensitivity is developed. GA is an efficient search method based on the mechanics of natural selection and population genetics. A simple GA is used where all features are mapped into binary chromosomes with a bit "1" representing the inclusion of the feature and a bit of "0" representing the absence of the feature. The performances of SA and GA are tested using two simulated non-linear time series and five real financial time series. The experiments show that with the simulated data, GA and SA detect the same true feature set from the redundant feature set, and the method of SA is also insensitive to the kernel function selection. With the real financial data, GA and SA select different subsets of features. Both selected feature sets achieve higher generation performance in SVMs than that of the full feature set. In addition, the generation performance between the selected feature sets of GA and SA is similar. All the results demonstrate that that both SA and GA are effective in SVMs for identifying important features.