PKCθ Regulates T Cell Motility via Ezrin-Radixin-Moesin Localization to the Uropod

Cell motility is a fundamental process crucial for function in many cell types, including T cells. T cell motility is critical for T cell-mediated immune responses, including initiation, activation, and effector function. While many extracellular receptors and cytoskeletal regulators have been shown to control T cell migration, relatively few signaling mediators have been identified that can modulate T cell motility. In this study, we find a previously unknown role for PKCθ in regulating T cell migration to lymph nodes. PKCθ localizes to the migrating T cell uropod and regulates localization of the MTOC, CD43 and ERM proteins to the uropod. Furthermore, PKCθ-deficient T cells are less responsive to chemokine induced migration and are defective in migration to lymph nodes. Our results reveal a novel role for PKCθ in regulating T cell migration and demonstrate that PKCθ signals downstream of CCR7 to regulate protein localization and uropod formation.</p

Linkage analysis of three families with arrythmogenic right ventricular cardiomyopathy in India

Background: Arrythmogenic Right Ventricular Cardiomyopathy (ARVC) is a primary myocardial disorder morphologically characterized by subtle to severe replacement of the right ventricular myocardium by fatty and fibrous tissue. ARVC is known to be highly prevalent in European population with recent reports implicating it to be a major cause of sudden death in young individuals even from American and Asian population. Aim: To implicate or exclude TMEM43 (ARVC-5), DSP(ARVC-8) genes and the yet to be identified gene at ARVC-6 locus in the pathogenesis in three families affected with ARVC from India. Materials and Methods: Three families comprising of 42 affected/unaffected members were included in the study. Three microsatellite markers, D3S3613 (ARVC5) D10S1664 (ARVC6), D6S309 (ARVC8) were genotyped by PCR-based native PAGE. Two-point Linkage analysis was performed using LINKAGE program version 5.2 . Results and Discussion: LOD scores from linkage analysis for the microsatellite marker D10S1664 (ARVC-6) in families KS and REV have shown positive value hinting the involvement of this locus in the etiology of ARVC, while linkage analysis in the SB family ruled out involvement of DSP, TMEM43 and ARVC-6, as negative LOD scores were obtained with all three loci. Therefore, linkage analysis carried out in the present study indicates that ARVC-6 (cumulative LOD score is equal to plus 1.203376 at q is equal to 0.05) could be the locus harboring the mutated gene in two out of three families

Pregled AC-DC i DC-DC pretvarača za primjene u LED rasvjeti

High-Brightness Light Emitting Diodes (HB-LEDs) are considered the future trend in lighting not only due to their high efficiency and high reliability, but also due to their other outstanding characteristics: chromatic variety, shock and vibration resistance, etc. Nevertheless, they need the development of new power supplies especially designed for boosting and taking advantage of their aforementioned characteristics. Besides, their behaviour is completely different from the rest of lighting devices and, consequently, it should be also taken into account in the design of the converters used to drive them. As a result, many well-known topologies have been optimized or redesigned in order to be used in LED–lighting applications and many new topologies have come up in the recent years with the same purpose. In this paper, the main HB-LED characteristics will be explained, highlighting how they influence the design of their power supplies. After, the main topologies will be presented from the simplest to the most complex ones, analysing their advantages and disadvantages.Svjetleće diode s visokom razinom svjetline (HB-LED) smatraju se budućim trendom u rasvjeti zahvaljujući ne samo visokom stupnju efikasnosti i pouzdanosti, nego i njihovim izvanrednim svojstvima: raznolikost boja, otpornost na udarce i vibracije i sl. Ipak, s ciljem potpunog iskorištenja prethodno spomenutih svojstava, potrebno je razviti nove, posebno osmišljene izvore napajanja. Osim toga, ponašanje im se posve razlikuje od ostalih tipova rasvjete što je potrebno uzeti u obzir pri projektiranju pretvarača za njihovo napajanje. Kao posljedica toga, mnoge su poznate topologije pretvarača optimirane ili preoblikovane posebno za primjenu u LED rasvjeti, a zadnjih nekoliko godina mnoge nove su se tek pojavile. U ovom članku objašnjena su osnovna HB-LED svojstva naglašavajući njihov utjecaj na razvoj izvora napajanja. Uz to, prikazane su osnovne topologije, od najjednostavnijih do najsloženijih, ujedno analizirajući prednosti i nedostatke pojedinih

nSeP: immune and metabolic biomarkers for early detection of neonatal sepsis-protocol for a prospective multicohort study

Introduction Diagnosing neonatal sepsis is heavily dependent on clinical phenotyping as culture-positive body fluid has poor sensitivity, and existing blood biomarkers have poor specificity. A combination of machine learning, statistical and deep pathway biology analyses led to the identification of a tripartite panel of biologically connected immune and metabolic markers that showed greater than 99% accuracy for detecting bacterial infection with 100% sensitivity. The cohort study described here is designed as a large-scale clinical validation of this previous work. Methods and analysis This multicentre observational study will prospectively recruit a total of 1445 newborn infants (all gestations)—1084 with suspected early—or late-onset sepsis, and 361 controls—over 4 years. A small volume of whole blood will be collected from infants with suspected sepsis at the time of presentation. This sample will be used for integrated transcriptomic, lipidomic and targeted proteomics profiling. In addition, a subset of samples will be subjected to cellular phenotype and proteomic analyses. A second sample from the same patient will be collected at 24 hours, with an opportunistic sampling for stool culture. For control infants, only one set of blood and stool sample will be collected to coincide with clinical blood sampling. Along with detailed clinical information, blood and stool samples will be analysed and the information will be used to identify and validate the efficacy of immune-metabolic networks in the diagnosis of bacterial neonatal sepsis and to identify new host biomarkers for viral sepsis

Differences in access to Emergency Paediatric Intensive Care and care during Transport (DEPICT): study protocol for a mixed methods study

Introduction Following centralisation of UK paediatric intensive care, specialist retrieval teams were established who travel to general hospitals to stabilise and transport sick children to regional paediatric intensive care units (PICUs). There is national variation among these PICU retrieval teams (PICRTs) in terms of how quickly they reach the patient’s bedside and in the care provided during transport. The impact of these variations on clinical outcomes and the experience of stakeholders (patients, families and healthcare staff) is however unknown. The primary objective of this study is to address this evidence gap. Methods and analysis This mixed-methods project involves the following: (1) retrospective analysis of linked data from routine clinical audits (2014–2016) to assess the impact of service variations on 30-day mortality and other secondary clinical outcomes; (2) a prospective questionnaire study conducted at 24 PICUs and 9 associated PICRTs in England and Wales over a 12-month period in 2018 to collect experience data from parents of transported children as well as qualitative analysis of in-depth interviews with a purposive sample of patients, parents and staff to assess the impact of service variations on patient/family experience; (3) health economic evaluation analysing transport service costs (and other associated costs) against lives saved and longer term measurements of quality of life at 12 months in transported children and (4) mathematical modelling evaluating the costs and potential impact of different service configurations. A final work stream involves a series of stakeholder workshops to synthesise study findings and generate recommendations. Ethics and dissemination The study has been reviewed and approved by the Health Research Authority, ref: 2 18 569. Study results will be actively disseminated through peer-reviewed journals, conference presentations, social media, print and broadcast media, the internet and stakeholder workshops

Single-phase parallel power processing scheme with power factor control

International Journal of Electronics802291-306IJEL

Evaluation of power losses in a boost PFC unit by temperature measurements

10.1109/TIA.2007.904431IEEE Transactions on Industry Applications4351320-1328ITIA

Existence results for classes of <inline-formula><graphic file="1687-2770-2006-87483-i1.gif"/></inline-formula>-Laplacian semipositone equations

<p/> <p>We study positive <inline-formula><graphic file="1687-2770-2006-87483-i2.gif"/></inline-formula> solutions to classes of boundary value problems of the form <inline-formula><graphic file="1687-2770-2006-87483-i3.gif"/></inline-formula> in <inline-formula><graphic file="1687-2770-2006-87483-i4.gif"/></inline-formula> on <inline-formula><graphic file="1687-2770-2006-87483-i5.gif"/></inline-formula>, where <inline-formula><graphic file="1687-2770-2006-87483-i6.gif"/></inline-formula> denotes the <inline-formula><graphic file="1687-2770-2006-87483-i7.gif"/></inline-formula>-Laplacian operator defined by <inline-formula><graphic file="1687-2770-2006-87483-i8.gif"/></inline-formula>; <inline-formula><graphic file="1687-2770-2006-87483-i9.gif"/></inline-formula>, <inline-formula><graphic file="1687-2770-2006-87483-i10.gif"/></inline-formula> is a parameter, <inline-formula><graphic file="1687-2770-2006-87483-i11.gif"/></inline-formula> is a bounded domain in <inline-formula><graphic file="1687-2770-2006-87483-i12.gif"/></inline-formula>; <inline-formula><graphic file="1687-2770-2006-87483-i13.gif"/></inline-formula> with <inline-formula><graphic file="1687-2770-2006-87483-i14.gif"/></inline-formula> of class <inline-formula><graphic file="1687-2770-2006-87483-i15.gif"/></inline-formula> and connected (if <inline-formula><graphic file="1687-2770-2006-87483-i16.gif"/></inline-formula>, we assume that <inline-formula><graphic file="1687-2770-2006-87483-i17.gif"/></inline-formula> is a bounded open interval), and <inline-formula><graphic file="1687-2770-2006-87483-i18.gif"/></inline-formula> for some <inline-formula><graphic file="1687-2770-2006-87483-i19.gif"/></inline-formula> (semipositone problems). In particular, we first study the case when <inline-formula><graphic file="1687-2770-2006-87483-i20.gif"/></inline-formula> where <inline-formula><graphic file="1687-2770-2006-87483-i21.gif"/></inline-formula> is a parameter and <inline-formula><graphic file="1687-2770-2006-87483-i22.gif"/></inline-formula> is a <inline-formula><graphic file="1687-2770-2006-87483-i23.gif"/></inline-formula> function such that <inline-formula><graphic file="1687-2770-2006-87483-i24.gif"/></inline-formula>, <inline-formula><graphic file="1687-2770-2006-87483-i25.gif"/></inline-formula> for <inline-formula><graphic file="1687-2770-2006-87483-i26.gif"/></inline-formula> and <inline-formula><graphic file="1687-2770-2006-87483-i27.gif"/></inline-formula> for <inline-formula><graphic file="1687-2770-2006-87483-i28.gif"/></inline-formula>. We establish positive constants <inline-formula><graphic file="1687-2770-2006-87483-i29.gif"/></inline-formula> and <inline-formula><graphic file="1687-2770-2006-87483-i30.gif"/></inline-formula> such that the above equation has a positive solution when <inline-formula><graphic file="1687-2770-2006-87483-i31.gif"/></inline-formula> and <inline-formula><graphic file="1687-2770-2006-87483-i32.gif"/></inline-formula>. Next we study the case when <inline-formula><graphic file="1687-2770-2006-87483-i33.gif"/></inline-formula> (logistic equation with constant yield harvesting) where <inline-formula><graphic file="1687-2770-2006-87483-i34.gif"/></inline-formula> and <inline-formula><graphic file="1687-2770-2006-87483-i35.gif"/></inline-formula> is a <inline-formula><graphic file="1687-2770-2006-87483-i36.gif"/></inline-formula> function that is allowed to be negative near the boundary of <inline-formula><graphic file="1687-2770-2006-87483-i37.gif"/></inline-formula>. Here <inline-formula><graphic file="1687-2770-2006-87483-i38.gif"/></inline-formula> is a <inline-formula><graphic file="1687-2770-2006-87483-i39.gif"/></inline-formula> function satisfying <inline-formula><graphic file="1687-2770-2006-87483-i40.gif"/></inline-formula> for <inline-formula><graphic file="1687-2770-2006-87483-i41.gif"/></inline-formula>, <inline-formula><graphic file="1687-2770-2006-87483-i42.gif"/></inline-formula>, and <inline-formula><graphic file="1687-2770-2006-87483-i43.gif"/></inline-formula>. We establish a positive constant <inline-formula><graphic file="1687-2770-2006-87483-i44.gif"/></inline-formula> such that the above equation has a positive solution when <inline-formula><graphic file="1687-2770-2006-87483-i45.gif"/></inline-formula> Our proofs are based on subsuper solution techniques.</p

A unity power factor converter using half-bridge boost topology

10.1109/63.668112IEEE Transactions on Power Electronics133487-500ITPE