HLA Class I alleles associated with HCV polymorphisms and response to antiviral therapy in HCV genotype 1-infected patients

Aims: The adaptive immune response against hepatitis C virus (HCV) is significantly shaped by the host's composition of HLA alleles. Thus, the HLA phenotype is a critical determinant of viral evolution during adaptive immune pressure. Potential associations of HLA class I alleles with polymorphisms of HCV immune escape variants are largely unknown. Methods: Direct sequence analysis of the genes encoding the HCV proteins E2, NS3 and NS5B in a cohort of 159 patients with chronic HCV genotype 1 infection who were treated with pegylated interferon-alfa 2b and ribavirin in a prospective controlled trial for 48 weeks was exhibited. HLA class I genotyping was performed by strand-specific reverse hybridization with the INNO-LiPA line probe assays for HLA-A and HLA-B and by strand-specific PCR-SSP. We analyzed each amino acid position of HCV proteins using an extension of Fisher's exact test for associations with HLA alleles. In addition, associations of specific HLA alleles with inflammatory activity, liver fibrosis, HCV RNA viral load and virologic treatment outcome were investigated. Results: Separate analyses of HCV subtype 1a and 1b isolates revealed substantially different patterns of HLA-restricted polymorphisms between subtypes. Only one polymorphism within NS5B (V2758x) was significantly associated with HLA B*15 in HCV genotype 1b infected patients (adjusted p=0,048). However, a number of HLA class I-restricted polymorphisms within novel putative HCV CD8+ T cell epitopes (genotype 1a: HLA-A*11 GTRTIASPK1086-1094 [NS3], HLA-B*07 WPAPQGARSL1111-1120 [NS3]; genotype 1b: HLA-A*24 HYAPRPCGI488-496 [E2], HLA-B*44 GENETDVLL530-538 [E2], HLA-B*15 RVFTEAMTRY2757-2766 [NS5B]) were observed with high predicted epitope binding scores assessed by the web-based software SYFPEITHI (>21). Most of the identified putative epitopes were overlapping with already otherwise published epitopes, indicating a high immunogenicity of the accordant HCV protein region. In addition, certain HLA class I alleles were associated with inflammatory activity, stage of liver fibrosis, and sustained virologic response to antiviral therapy. Conclusions: HLA class I restricted HCV sequence polymorphisms are rare. HCV polymorphisms identified within putative HCV CD8+ T cell epitopes in the present study differ in their genomic distribution between genotype 1a and 1b isolates, implying divergent adaptation to the host's immune pressure on the HCV subtype level.

Agenda d'actes i gestió fotogràfica web

L'objectiu principal d'aquest projecte ha estat aprofundir en la construcció de programari, abordant totes les etapes d'un projecte de construcció de programari des de la perspectiva de l'enginyeria del software (anàlisi, disseny, implementació i proves) i utilitzant el paradigma de programació Orientada a l'Objecte mitjançant l'ús de la tecnologia J2EE, conjuntament amb bastions de programari de gran importància en el mon real i per tant, en l'àmbit de desenvolupament de programari i tecnològic actuals.

GateKeeper - Käyttäjienhallintaohjelma

Tämän insinöörityön tavoitteena oli suunnitella ja toteuttaa selainpohjainen käyttäjienhallintaohjelma GateKeeper Karttakeppi.com-työryhmälle. GateKeeper-ohjelma kuuluu osana laajempaan ohjelmistoprojektiin, jonka tarkoituksena on tuottaa opetusmateriaalia etäopiskelijoille Internetissä. Etäopetusmateriaalin tuottamisessa käytetään useita ohjelmia, joille on määriteltävä eritasoisia käyttäjätunnuksia ja käyttöoikeuksia. Ohjelmien käyttäjienhallintamekanismit ovat erilaisia, mikä osaltaan lisää järjestelmän ylläpitäjien työtä ja vastuuta. GateKeeper-ohjelman tavoitteena on nopeuttaa, helpottaa ja yksinkertaistaa käyttäjienhallintaan liittyviä toimintoja tietoturvallisesti. GateKeeper-ohjelma on suunniteltu siten, että uusien käyttäjien ja ohjelmien lisäämiselle ei ole asetettu rajoja. Jokaisen lisättävän ohjelman yhteydessä on kuitenkin selvitettävä kyseisen ohjelman käyttäjienhallintamekanismi. Tässä insinöörityössä tutkittiin, miten versionhallintaohjelma Subversionin, julkaisujärjestelmä Mambon, sekä oppimisalusta Moodlen käyttäjiä voidaan keskitetysti hallinnoida GateKeeper-ohjelman avulla. GateKeeper-ohjelma noudattaa arkkitehtuuriltaan kolmikerrosmallia, jossa käyttöliittymä, sovelluslogiikka ja tietovarasto on erotettu toisistaan. Ohjelma koostuu joukosta PHP-kielellä toteutettuja dynaamisia web-sivuja. Tietovarastona käytetään tietokantapalvelimella sijaitsevaa MySQL-tietokantaa.

Gestión de citas médicas en un pequeño ambulatorio

Este TFC trata sobre la gestión de citas médicas en un pequeño ambulatorio o centro médico.

Mantenimiento preventivo

Análisis y diseño de una aplicación informática que cubre las necesidades del mantenimiento preventivo de una planta de producción.

Gestió i pagaments digitals

En aquest projecte es contempla la creació d'un portal de gestió de cobraments i pagaments dins del marc de la certificació digital que es basa en la implantació del estàndard e-factura que es reconeix a Espanya.

Anàlisi i disseny d'un programari per a la gestió d'un viver de plantes ornamentals

Projecte per a la creació d'un programari per a un viver de plantes auto-gestionat amb l'ajuda d'elements de control i interactuació amb les instal·lacions i els sistemes de reg i fertilització.

Proyecto de implementación de una webapp para una agencia de viajes

Elaboración de un proyecto en el que se ha creado la documentación completa de una aplicación web para una agencia de viajes ficticia para la consulta y reserva de los productos que desea ofrecer a sus clientes.

Influence of chronic hyperglycemia on cerebral microvascular remodeling: an in vivo study using perfusion computed tomography in acute ischemic stroke patients.

BACKGROUND AND PURPOSE: To investigate the effect of chronic hyperglycemia on cerebral microvascular remodeling using perfusion computed tomography. METHODS: We retrospectively identified 26 patients from our registry of 2453 patients who underwent a perfusion computed tomographic study and had their hemoglobin A1c (HbA1c) measured. These 26 patients were divided into 2 groups: those with HbA1c>6.5% (n=15) and those with HbA1c≤6.5% (n=11). Perfusion computed tomographic studies were processed using a delay-corrected, deconvolution-based software. Perfusion computed tomographic values were compared between the 2 patient groups, including mean transit time, which relates to the cerebral capillary architecture and length. RESULTS: Mean transit time values in the nonischemic cerebral hemisphere were significantly longer in the patients with HbA1c>6.5% (P=0.033), especially in the white matter (P=0.005). Significant correlation (R=0.469; P=0.016) between mean transit time and HbA1c level was observed. CONCLUSIONS: Our results from a small sample suggest that chronic hyperglycemia may be associated with cerebral microvascular remodeling in humans. Additional prospective studies with larger sample size are required to confirm this observation.

Sistema de control per a línies de producció

Creació d'un sistema per al control d'una línia de producció des del punt de vista de l'enginyeria del programari.

Migración M.O.S.S. 2007 a SharePoint 2010 de Hospital Universitario Virgen del Rocío

En el presente trabajo se ha descrito el análisis y diseño que motiva el proyecto de migración de Microsoft SharePoint Server 2007 a la versión SharePoint Server 2010 que desarrolla la intranet de uno de los mayores complejos hospitalarios de nuestro país.

Gestión de gastos personales

Con el proyecto se pretende generar un software que permite a todos los empleados de una empresa poder gestionar de una manera eficiente el pago de los gastos personales.

Disseny d'una eina de gestió d'un planificador d'execucions batch

L'abast d'aquest projecte es centrarà en el disseny d'una eina de gestió d'un planificador d'execucions batch, que intentarà donar una solució independent de l'entorn on s'executen aquests processos i que servirà com a eina de suport a un equip d'analistes i dissenyadors que creïn o mantinguin aquests processos.

SiMR: A simulator for learning computer architecture

This paper presents SiMR, a simulator of the Rudimentary Machine designed to be used in a first course of computer architecture of Software Engineering and Computer Engineering programmes. The Rudimentary Machine contains all the basic elements in a RISC computer, and SiMR allows editing, assembling and executing programmes for this processor. SiMR is used at the Universitat Oberta de Catalunya as one of the most important resources in the Virtual Computing Architecture and Organisation Laboratory, since students work at home with the simulator and reports containing their work are automatically generated to be evaluated by lecturers. The results obtained from a survey show that most of the students consider SiMR as a highly necessary or even an indispensable resource to learn the basic concepts about computer architecture.