Miracle-dz/UniFAR-FTUs huggingface dataset:
A noncanonical SH3 domain binding motif links BK channels to the actin cytoskeleton via the SH3 adapter cortactin

Calcium‐activated potassium (BK) channels play a central role in regulating multiple physiological processes, from the control of blood flow to neuronal excitability. Coordinated regulation of BK channel activity by changes in actin cytoskeleton dynamics has been implicated in several of these processes and related disease states such as epilepsy and stroke. However, how BK channels interact with the actin cytoskeleton is essentially unknown. Here we demonstrate noncanonical Src homology domain 3 (SH3) binding site motifs in the intracellular C terminus of the BK channel pore‐forming α‐subunit that are conserved from fish to humans. These noncanonical motifs target multiple SH3 domain cellular signaling proteins to BK channels, including the SH3 adapter protein cortactin (EMS1). We demonstrate that cortactin provides a molecular bridge between BK channels and the cortical actin cytoskeleton in cells. Disruption of the SH3‐mediated interaction prevents the regulation of BK channel activity controlled by changes in actin cytoskeletal dynamics. Targeting of cortactin to BK channels via a novel, noncanonical SH3 domain binding motif has important implications for the coordination of BK channel function in normal physiology and disease. —Tian, L. , Chen, L. , McClafferty, H. , Sailer, C. A. , Ruth, P., Knaus, H‐G. , Shipston, M. J. A noncanonical SH3 domain binding motif links BK channels to the actin cytoskeleton via the SH3 adapter cortactin. FASEB J. 20, E2046–E2056 (2006)
Penalized differential pathway analysis of integrative oncogenomics studies

Abstract Through integration of genomic data from multiple sources, we may obtain a more accurate and complete picture of the molecular mechanisms underlying tumorigenesis. We discuss the integration of DNA copy number and mRNA gene expression data from an observational integrative genomics study involving cancer patients. The two molecular levels involved are linked through the central dogma of molecular biology. DNA copy number aberrations abound in the cancer cell. Here we investigate how these aberrations affect gene expression levels within a pathway using observational integrative genomics data of cancer patients. In particular, we aim to identify differential edges between regulatory networks of two groups involving these molecular levels. Motivated by the rate equations, the regulatory mechanism between DNA copy number aberrations and gene expression levels within a pathway is modeled by a simultaneous-equations model, for the one- and two-group case. The latter facilitates the identification of differential interactions between the two groups. Model parameters are estimated by penalized least squares using the lasso (L1) penalty to obtain a sparse pathway topology. Simulations show that the inclusion of DNA copy number data benefits the discovery of gene-gene interactions. In addition, the simulations reveal that cis-effects tend to be over-estimated in a univariate (single gene) analysis. In the application to real data from integrative oncogenomic studies we show that inclusion of prior information on the regulatory network architecture benefits the reproducibility of all edges. Furthermore, analyses of the TP53 and TGFb signaling pathways between ER+ and ER- samples from an integrative genomics breast cancer study identify reproducible differential regulatory patterns that corroborate with existing literature.
Identification of factors that influence tolerance of upper gastrointestinal endoscopy.

OBJECTIVE Unsedated gastroscopy is unpleasant for some patients. The identification of factors related to tolerance would permit the selection of patients for sedation. The aim of the present study was to identify these factors. METHODS Five hundred and nine patients underwent diagnostic gastroscopy after the administration of topical pharyngeal anaesthesia, without sedation. Patients were grouped as to whether they had undergone prior examinations or not. Tolerance was assessed with a visual analogue scale and a questionnaire. RESULTS Two hundred and seventy-three (54%) patients underwent gastroscopy for the first time, and 236 (46%) patients had prior experience. Patient tolerance was poor in 84 of 273 (31%) patients undergoing gastroscopy for the first time, and in 61 of 236 (26%) patients with prior experience. Logistic regression analysis identified the following variables related to poor tolerance: (a) in patients undergoing gastroscopy for the first time: presence of gag reflex (odds ratio (OR) = 3.42, 95% confidence interval (CI) 1.90-6.17), apprehension (OR = 2.57, CI 1.33-4.95), young age (OR = 0.95, CI 0.93-0.98) and high level of anxiety (OR = 1.91, CI 0.96-3.89); (b) in patients with prior experience: apprehension (OR = 4.21, CI 1.93-9.20), poor tolerance of prior examinations (OR = 4.92, CI 1.93-12.5) and female (OR = 2.23, CI 1.09-4.57). CONCLUSIONS The above-mentioned factors are predictive of poor tolerance, and may enable the identification of those patients who might benefit more from sedation for gastroscopy.
Opinions among Danish knee surgeons about indications to perform total knee replacement showed considerable variation.

INTRODUCTION During the past decade, the incidence of primary total knee replacement (TKA) surgery in Denmark has approximately doubled. This increase could be due to weakened indications to perform TKA surgery. We aimed to investigate variation in opinions about indications to perform TKA among Danish knee surgeons. MATERIAL AND METHODS In October 2011, a survey among Danish knee surgeons was performed at the Annual Meeting of the Danish Orthopaedic Society. A questionnaire targeting knee surgeons' opinion on indications for primary TKA was distributed. Questions concerned opinions on aspects of pain, body mass index (BMI), exercise, function, age, clinical and radiographic findings, and specific patient cases. RESULTS A total of 41 questionnaires were returned. Twenty-three knee surgeons performed > 100 TKAs annually. Opinions about the duration of knee pain and pain treatment, preoperative weight loss and exercise, excessive BMI as a contraindication, low age as a contraindication, and some of the specific patient cases demonstrated considerable variation. A statistically significantly higher proportion of high-volume versus low-volume knee surgeons did not find that BMI could be a contraindication to proceed with TKA surgery (p = 0.02). CONCLUSION Opinions among knee surgeons about indications to perform TKA showed considerable variation. The majority of the variation observed is tolerable and may be explained by lack of evidence or diverging literature reports. However, variation in opinions regarding preoperative weight loss and exercise may warrant the introduction of further guidelines for involved care takers. FUNDING not relevant. TRIAL REGISTRATION not relevant.
Effects of phosphatidylinositol-3-kinase inhibitors on degranulation and gene induction in allergically triggered mouse mast cells.

BACKGROUND Phosphatidylinositol-3-kinase (PI3-kinase) comprises an essential component in a number of signaling cascades, primarily of the growth factor type. Two specific inhibitors, wortmannin and demethoxyviridin (DMV), are widely used to block signaling via this molecule and link certain receptors to the PI3-kinase pathway. METHODS We have studied the extent of involvement of PI3-kinase in signaling events by Fc epsilonRI in mast cells using a mouse mast cell line as a model system. This was done using beta-hexosaminidase release assays, a leukotriene ELISA, transient transfections with reporter gene constructs of TNF alpha and MARC, and in addition a TNF alpha ELISA. RESULTS Consistent with previously published data in the rat basophilic cell line RBL-2H3, we find that wortmannin as well as DMV prevent the degranulation reaction in the mouse mast cell line CPII. DMV also inhibits the release of leukotrienes, leading to the conclusion that Fc epsilonRI activates PI3-kinase which then mediates these reactions. On the contrary, however, lymphokine and chemokine induction at the gene and protein level is not inhibited, suggesting that the activation of this gene set in mast cells is independent of PI3-kinase. CONCLUSION PI3-kinase is activated in our mast cell model system via cross-linking of the Fc epsilonRI. This reaction is clearly necessary for the degranulation process and the release of leukotrienes. Activation of lymphokine and chemokine genes as well as secretion of their gene products are not triggered along the PI3-kinase signaling pathway. This is in agreement with our previous findings, showing that the MAP kinase pathway and Ca2+ influx are both involved in gene activation in this cell type.
Comparison of the Efficacy of CO2-Baited and Unbaited Light Traps, Gravid Traps, Backpack Aspirators, and Sweep Net Collections for Sampling Mosquitoes Infected with Japanese Encephalitis Virus

ABSTRACT: Two field studies were conducted to determine the efficacy of mosquito collection methods for species composition, species abundance, and Japanese encephalitis virus infection rates in Taiwan. Traps evaluated included John W. Hock (JH) model UD black light traps, JH model 1012 new standard miniature CDC light traps, JH model 1712 CDC gravid traps, and Taiwan-made Pest-O-Lite light traps. Backpack aspirators and sweep nets were also used to collect the resting population. Culex tritaeniorhynchus in all studies and Mansonia uniformis in the Taipei areas were the two most abundance species collected. Dry ice-baited UD black light traps were effective in regard to species diversity, species abundance, and Japanese encephalitis virus infection rates. The unbaited Pest-O-Lite light traps collected significantly more female mosquitoes than the UD black light traps but performed similarly with regard to species diversity and male mosquito collection. Most mosquitoes collected by Pest-O-Lite light traps were dried and not suitable for virus detection. Dry ice-baited CDC light traps collected significantly fewer mosquitoes than other light traps. Although CO2-baited UD black light traps with octenol attracted more mosquitoes, no statistical significance was found compared to CO2-baited UD black light traps without octenol. Japanese encephalitis viruses were isolated from half of the positive pools in UD black light traps and CDC light traps.
Hepatitis C virus genotypes in chronic dialysis patients.

BACKGROUND Hepatitis C virus (HCV) infection is highly prevalent in dialysis patients. To further characterize HCV infection in this patient population, we studied the distribution of viral genotypes in 55 patients undergoing chronic dialysis treatment with seropositivity for HCV markers. METHODS Thirty-two of 55 (58%) patients showed HCV RNA in the serum using reverse transcription polymerase chain reaction (RT-PCR) in the 5'-untranslated region (UTR) of the viral genome. HCV genotyping was performed using biotinylated type-specific oligonucleotide probes after hybridization with amplified sample material. RESULTS HCV subtype 2a was dominant (56%), followed by HCV subtype 1b (31%), type 3 (3%) and 4 (3%). There was no association between demographic or clinical features of this cohort and HCV genotype. Genotype dependence was observed for antibody response toward the NS4 (c 100-3 and 5-1-1) proteins, which was infrequent in genotype 2a carriers compared with genotype 1b (p = 0.004). CONCLUSIONS HCV subtype 2a was dominant in our cohort of anti-HCV-positive dialysis patients; there was no association between HCV genotypes and demographic or clinical features of patients; the absence of antibody response toward the NS4-related antigens was frequent in genotype 2a carriers and may serve to predict responses to interferon therapy. The relative homogeneity of the viral population in dialysis patients attending our unit suggests a nosocomial transmission of HCV in this clinical setting.
Multi-target tracking in clutter without measurement assignment

When tracking targets using radars and sonars, the number of targets and the origin of data is uncertain. Data may be false measurements or clutter, or they may be detections from an unknown number of targets whose possible trajectories and detection processes can only be described in a statistical manner. Optimal all-neighbor multi-target tracking (MTT) in clutter enumerates all possible joint measurement-to-track assignments and calculates the a posteriori probabilities of each of these joint assignments. The numerical complexity of this process is combinatorial in the number of tracks and the number of measurements. One of the key differences between most MTT algorithms is the manner in which they reduce the computational complexity of the joint measurement-to-track assignment process. We propose an alternative approach, using a form of soft assignment, that enables us to bypass this step entirely. Specifically, our approach treats possible detections of targets followed by other tracks as additional clutter measurements. It starts by approximating the a~priori probabilities of measurement origin. These probabilities are then used to modify the clutter spatial density at the location of the measurements. A suitable single target tracking (STT) filter then uses the modified clutter intensity for updating the track state. In effect, the STT filter is transformed into an MTT filter with a numerical complexity that is linear in the number of tracks and the number of measurements. Simulations show the effectiveness of this approach in a number of different multi-target scenarios.
New approaches for treating staphylococcal biofilm infections

Bacteria of the genus Staphylococcus are a prominent cause of acute and chronic infections. The ability of the staphylococci to establish biofilms has been linked to the persistence of chronic infections, which has drawn considerable interest from researchers over the past decade. Biofilms can be defined as sessile communities of surface‐attached cells encased in an extracellular matrix, and treatment of bacteria in this mode of growth is challenging due to the resistance of biofilm structures to both antimicrobials and host defenses. In this review of the literature, we introduce Staphylococcus aureus and Staphylococcus epidermidis biofilms and summarize current antibiotic treatment approaches for staphylococcal biofilm infections. We also review recent studies on alternative strategies for preventing biofilm formation and dispersing established biofilms, including matrix‐degrading enzymes, small‐molecule approaches, and manipulation of natural staphylococcal disassembly mechanisms. While research on staphylococcal biofilm development is still in its early stages, new discoveries in the field hold promise for improved therapies that target staphylococcal biofilm infections.
A Consumer Satisfaction Survey of Civilly Committed Sex Offenders in Illinois

The purpose of this study was to obtain feedback from civilly committed sex offenders (N = 113) about the components of treatment that they believed to be most important and helpful in preventing reoffense. Participants were also asked to rate their satisfaction with the treatment process and therapists. Victim empathy and accountability were rated as the most important elements of treatment, along with skills for preventing relapse and methods for controlling sexual arousal. There was a fairly robust correlation between client perceptions of importance and satisfaction on most treatment components. Some clients expressed concerns about respect, confidentiality, and judgmental attitudes of some therapists. Because civilly committed sex offenders are considered to be among the most likely to reoffend, strategies are discussed for engagement of this population in a meaningful process of change.
Centralized Pan-European Survey on the Undertreatment of Hypercholesterolemia in Patients Using Lipid Lowering Drugs–The CEPHEUS-Greece Survey

Surveys evaluating plasma lipid goal attainment in patients with coronary heart disease (CHD) show that hypercholesterolemia is inadequately treated. CEPHEUS (CEntralized Pan-European survey on tHE Undertreatment of hypercholeSterolemia)-Greece was part of a European multicenter, cross-sectional survey to evaluate the proportion of patients on lipid-lowering drugs (LLDs) for ≥3 months, without dose modifications for at least 6 weeks, who reach their low-density lipoprotein—cholesterol (LDL-C) target. A total of 1321 Greek patients comprised the full analysis set (FAS); 28% were smokers, while 60.7%, 35.4%, 32.1%, and 25.1% had a history of hypertension, CHD, metabolic syndrome, and diabetes mellitus, respectively; 49.7% of the study population reached the Third Joint European Task Force (TJETF) LDL-C goals and 49.3% achieved the 2004-updated National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) targets. Hypercholesterolemia is suboptimally managed in Greece, with almost 50% of patients on LLDs not reaching the LDL-C target.
Multiferroic thin-film integration onto semiconductor devices

This review deals with thin films of single-phase materials which exhibit two primary ferroic properties, namely ferroelectricity and (anti)ferromagnetism, deposited directly or through buffer layers onto semiconductors. It is the electrical control of ferromagnetism and magnetic control of ferroelectricity at room temperature and resulting device functionality that served as the driving force for the recent widespread research activities in this field. Although Gilbert demonstrated in 1600 that electrostatics (amber) do not couple to magnetostatics (compass needles), charges in motion certainly couple to magnetism, as shown later by Oersted and epitomized by Maxwell’s theoretical derivation of the properties of electromagnetic waves. We survey the important contributions of various eminent physicists, from Curie to Dzyaloshinskii and Astrov to Schmid, without whom this field of research might not have developed. Most of the known multiferroic materials are classified into different groups, primarily based on Khomskii’s classification of oxide multiferroics. We follow this with a brief discussion on the device application of multiferroics with semiconductor integration.
Why patients with inflammatory bowel disease use or do not use complementary and alternative medicine: a Canadian national survey.

BACKGROUND The use of complementary and alternative medicine (CAM) is common in patients with inflammatory bowel disease (IBD). OBJECTIVES To determine the factors associated with use of CAM, the reasons commonly cited for use or nonuse of CAM, and the correlations between the factors associated with use of CAM and reasons for CAM use. SUBJECTS The study included 2828 members of the Crohn's and Colitis Foundation of Canada. METHODS Subjects were mailed a questionnaire that included items on demographic characteristics, disease and treatment history, health attitudes and behaviours, and reasons for use or nonuse of CAM. Logistical regression was used to determine significant associations with current CAM use. RESULTS In patients with Crohn's disease and ulcerative colitis, CAM use was associated with more severe disease activity, use of CAM for other purposes, use of exercise and prayer for IBD, and a desire for an active role in treatment decisions. CAM use was also associated with younger age in those with Crohn's disease, and less confidence in their IBD physician in those with ulcerative colitis. The most common reasons for CAM use were a desire for greater control, having heard or read that CAM might help, and the emphasis CAM places on treating the whole person. The most common reasons for not using CAM were that conventional treatments were successful, that not enough was known about CAM and a belief that CAM would not help. CONCLUSION Disease activity and health attitudes and behaviours, but not demographic characteristics, are associated with CAM use by those with IBD.
New Avenues of Logistics and Transportation Laws in Supply Chain Management: Issues and Challenges

While dealing with trade, either at domestic or international market, legal considerations involve in logistics and transportation in supply chain has played their significant role. The field of laws and regulations has been emerged over time with some serious issues at global market. Present study has reviewed the opportunities with the issues and trends involved in logistics and transportation. For this purpose, a comprehensive review is developed with some meaningful suggestions to develop a comprehensive understanding as well. In this regard, the field of Operational research (OR), its historical trends, legal issues for the transportation of goods, international commercial terms, and finally the shipped documents are very much important. Although the complexity level has been increased while dealing with the legal formalities, the compliance of shipped documents can provide the firm with better outcome and better delivery of the products in recent time.
Equine Herpesvirus Type 4 UL56 and UL49.5 Proteins Downregulate Cell Surface Major Histocompatibility Complex Class I Expression Independently of Each Other

ABSTRACT Major histocompatibility complex class I (MHC-I) molecules are critically important in the host defense against various pathogens through presentation of viral peptides to cytotoxic T lymphocytes (CTLs), a process resulting in the destruction of virus-infected cells. Herpesviruses interfere with CTL-mediated elimination of infected cells by various mechanisms, including inhibition of peptide transport and loading, perturbation of MHC-I trafficking, and rerouting and proteolysis of cell surface MHC-I. In this study, we show that equine herpesvirus type 4 (EHV-4) modulates MHC-I cell surface expression through two different mechanisms. First, EHV-4 can lead to a significant downregulation of MHC-I expression at the cell surface through the product of ORF1, a protein expressed with early kinetics from a gene that is homologous to herpes simplex virus 1 UL56. The EHV-4 UL56 protein reduces cell surface MHC-I as early as 4 h after infection. Second, EHV-4 can interfere with MHC-I antigen presentation, starting at 6 h after infection, by inhibition of the transporter associated with antigen processing (TAP) through its UL49.5 protein. Although pUL49.5 has no immediate effect on overall surface MHC-I levels in infected cells, it blocks the supply of antigenic peptides to the endoplasmic reticulum (ER) and transport of peptide-loaded MHC-I to the cell surface. Taken together, our results show that EHV-4 encodes at least two viral immune evasion proteins: pUL56 reduces MHC-I molecules on the cell surface at early times after infection, and pUL49.5 interferes with MHC-I antigen presentation by blocking peptide transport in the ER.