Reverse immunology approach for the identification of CD8 T-cell-defined antigens: advantages and hurdles.

One of the challenges of tumour immunology remains the identification of strongly immunogenic tumour antigens for vaccination. Reverse immunology, that is, the procedure to predict and identify immunogenic peptides from the sequence of a gene product of interest, has been postulated to be a particularly efficient, high-throughput approach for tumour antigen discovery. Over one decade after this concept was born, we discuss the reverse immunology approach in terms of costs and efficacy: data mining with bioinformatic algorithms, molecular methods to identify tumour-specific transcripts, prediction and determination of proteasomal cleavage sites, peptide-binding prediction to HLA molecules and experimental validation, assessment of the in vitro and in vivo immunogenic potential of selected peptide antigens, isolation of specific cytolytic T lymphocyte clones and final validation in functional assays of tumour cell recognition. We conclude that the overall low sensitivity and yield of every prediction step often requires a compensatory up-scaling of the initial number of candidate sequences to be screened, rendering reverse immunology an unexpectedly complex approach.

A New Imaging Software To Evaluate The Centration Of Capsulorhexis And Intraocular Lens (IOL) After Cataract Surgery

Purpose: IOL centration and stability after cataract surgery is of high interest for cataract surgeons and IOL-producing companies. We present a new imaging software to evaluate the centration of the rhexis and the centration of the IOL after cataract surgery.Methods: We developed, in collaboration with the Biomedical Imaging Group (BIG), EPFL, Lausanne, a new working tool in order to assess precisely outcomes after IOL-implantation, such as ideal capsulorhexis and IOL-centration. The software is a plug-in of ImageJ, a general-purpose image processing and image-analysis package. The specifications of this software are: evaluation of the rhexis-centration and evaluation the position of the IOL in the posterior chamber. The end points are to analyze the quality of the centration of a rhexis after cataract surgery, the deformation of the rhexis with capsular bag retraction and the centration of the IOL after implantation.Results: This software delivers tools to interactively measure the distances between limbus, IOL and capsulorhexis and its changes over time. The user is invited to adjust nodes of three radial curves for the limbus, rhexis and the optic of the IOL. The radial distances of the curves are computed to evaluate the IOL implantation. The user is also able to define patterns for ideal capsulorhexis and optimal IOL-centration. We are going to present examples of calculations after cataract surgery.Conclusions: Evaluation of the centration of the rhexis and of the IOL after cataract surgery is an important end point for optimal IOL implantation after cataract surgery. Especially multifocal or accommodative lenses need a precise position in the bag with a good stability over time. This software is able to evaluate these parameters just after the surgery but also its changes over time. The results of these evaluations can lead to an optimizing of surgical procedures and materials.

Migración de servicios críticos: de plataformas propietarias a software libre

El objetivo principal del presente trabajo pretende demostrar el potencial del software libre frente al software propietario que actualmente utiliza la empresa Systemum.

Software para la representación gráfica a la solución de ruteo y carga de vehículos en algoritmo de tipo 2L-CVRP

El siguiente artículo presenta el trabajo realizado en la creación de una aplicación de software libre que representa gráficamente las rutas generadas y la distribución de los elementos transportados en el interior de un vehículo de carga.

Plasma and cerebrospinal fluid population pharmacokinetics of temozolomide in malignant glioma patients

RESUME : Objectif: Le glioblastome multiforme (GBM) est la tumeur cérébrale maligne la plus agressive qui conduit au décès de la majorité des patients moins d'une année après le diagnostic. La plupart des agents chimiothérapeutiques actuellement disponibles ne traversent pas la barrière hémato¬encéphalique et ne peuvent par conséquent pas être utilisés pour ce type de tumeur. Le Temozolomide (TMZ) est un nouvel agent alkylant récemment développé pour le traitement des gliomes malins. A ce jour, très peu d'informations sont disponibles sur la pénétration intra-cérébrale de cet agent. Au cours d'une étude pilote de phase II menée auprès de 64 patients atteints de GBM, l'administration précoce de TMZ combinée à une radiothérapie standard (RT) afin d'intervenir au plus tôt dans l'évolution de la maladie, a permis de prolonger la survie de ces patients, résultat qui pu être confirmé par la suite lors de l'étude randomisée de phase III. L'objectif de cette étude a été de déterminer les paramètres pharmacocinétique du TMZ dans le plasma et le liquide céphalo-rachidien (LCR), d'évaluer l'influence de certains facteurs individuels (âge, sexe, surface corporelle, fonction rénale/hépatique, co-médications, RT concomitante) sur ces différents paramètres, et enfin d'explorer la relation existant entre l'exposition au TMZ et certains marqueurs cliniques d'efficacité et de toxicité. Matériel et Méthode: Les concentrations de TMZ ont été mesurées par chromatographie liquide à haute performance (HPLC) dans le plasma et le LCR de 35 patients atteints de GBM nouvellement diagnostiqués (étude pilote) ou de gliomes malins en récidive (étude récidive). L'analyse pharmacocinétique de population a été réalisée à l'aide du programme NONMEM. L'exposition systémique et cérébrale, définie par les AUC (Area Under the time-concentration Curve) dans le plasma et le LCR, a été estimée pour chaque patient et corrélée à la toxicité, la survie ainsi que la survie sans progression tumorale. Résultats: Un modèle à 1 compartiment avec une cinétique d'absorption et de transfert Kplasma -> LCR de ordre a été retenu afin de décrire le profil pharmacocinétique du TMZ. Les valeurs moyennes de population ont été de 10 L/h pour la clairance, de 30.3 L pour le volume de distribution, de 2.1 h pour la 1/2 vie d'élimination, de 5.78 hE-1 pour la constante d'absorption, de 7.2 10E4 hE-1 pour Kplasma->LCR et de 0.76 hE-1 pour KLCR plasma. La surface corporelle a montré une influence significative sur la clairance et le volume de distribution, alors que le sexe influence la clairance uniquement. L'AUC mesurée dans le LCR représente ~20% de celle du plasma et une augmentation de 15% de Kplasma->LCR a été observée lors du traitement concomitant de radiochimiothérapie. Conclusions: Cette étude est la première analyse pharmacocinétique effectuée chez l'homme permettant de quantifier la pénétration intra-cérébrale du TMZ. Le rapport AUC LCR/AUC Plasma a été de 20%. Le degré d'exposition systémique et cérébral au TMZ ne semble pas être un meilleur facteur prédictif de la survie ou de la tolérance au produit que ne l'est la dose cumulée seule. ABSTRACT Purpose: Scarce information is available on the brain penetration of temozolomide (TMZ), although this novel methylating agent is mainly used for the treatment of ma¬lignant brain tumors. The purpose was to assess TNIZ phar¬macokinetics in plasma and cerebrospinal fluid (CSF) along with its inter-individual variability, to characterize covari¬ates and to explore relationships between systemic or cere¬bral drug exposure and clinical outcomes. Experimental Design: TMZ levels were measured by high-performance liquid chromatography in plasma and CSF samples from 35 patients with newly diagnosed or recurrent malignant gliomas. The population pharmacoki¬netic analysis was performed with nonlinear mixed-effect modeling software. Drug exposure, defined by the area un¬der the concentration-time curve (AUC) in plasma and CSF, was estimated for each patient and correlated with toxicity, survival, and progression-free survival. Results: A three-compartment model with first-order absorption and transfer rates between plasma and CSF described the data appropriately. Oral clearance was 10 liter/h; volume of distribution (VD), 30.3 liters; absorption constant rate, 5.8 hE-1; elimination half-time, 2.1 h; transfer rate from plasma to CSF (Kplasma->CSF), 7.2 x 10E-4hE-1 and the backwards rate, 0.76hE-1. Body surface area signifi¬cantly influenced both clearance and VD, and clearance was sex dependent. The AU CSF corresponded to 20% of the AUCplasma. A trend toward an increased K plasma->CSF of 15% was observed in case of concomitant radiochemo-therapy. No significant correlations between AUC in plasma or CSF and toxicity, survival, or progression-free survival were apparent after deduction of dose-effect. Conclusions: This is the first human pharmacokinetic study on TMZ to quantify CSF penetration. The AUC CSF/ AUC plasma ratio was 20%. Systemic or cerebral exposures are not better predictors than the cumulative dose alone for both efficacy and safety.

Implantació d'un ERP i una plataforma e-commerce de software lliure per al desenvolupament web d'una empresa

Aquest projecte constitueix la introducció d'un sistema d'informació a una PIME catalana. Incorporant dos grans i potents funcionalitats i serveis a l'empresa: la venta online mitjançant un e-commerce i la gestió de la informació i productes que hi ha a l'empresa mitjançant un ERP.

RestKiosk : Software d'autoservei per a restauració

Primera versió d'una aplicació per a establiments de restauració que té com a finalitat oferir als clients la possibilitat de fer les comandes de forma autònoma.

Avaliação de alunos e professores acerca do software "Sinais Vitais"

Este artigo teve por objetivo levantar as opiniões de alunos e professores sobre o software "Sinais Vitais". O trabalho foi desenvolvido no Departamento de Enfermagem da Universidade Federal do Ceará. Trabalhou-se com um total de seis alunos e três professores, os quais foram submetidos a uma entrevista após a utilização do software. As entrevistas geraram dez categorias, as quais foram separadas em dois temas: Características que estimularam a utilização do software "Sinais Vitais" e Software educacionalmente correto. Concluiu-se que os professores valorizaram a correção do conteúdo, enquanto os alunos enfocaram mais a dinâmica do programa.

Performance of classic electrocardiographic criteria for left ventricular hypertrophy in an African population.

ECG criteria for left ventricular hypertrophy (LVH) have been almost exclusively elaborated and calibrated in white populations. Because several interethnic differences in ECG characteristics have been found, the applicability of these criteria to African individuals remains to be demonstrated. We therefore investigated the performance of classic ECG criteria for LVH detection in an African population. Digitized 12-lead ECG tracings were obtained from 334 African individuals randomly selected from the general population of the Republic of Seychelles (Indian Ocean). Left ventricular mass was calculated with M-mode echocardiography and indexed to body height. LVH was defined by taking the 95th percentile of body height-indexed LVM values in a reference subgroup. In the entire study sample, 16 men and 15 women (prevalence 9.3%) were finally declared to have LVH, of whom 9 were of the reference subgroup. Sensitivity, specificity, accuracy, and positive and negative predictive values for LVH were calculated for 9 classic ECG criteria, and receiver operating characteristic curves were computed. We also generated a new composite time-voltage criterion with stepwise multiple linear regression: weighted time-voltage criterion=(0.2366R(aVL)+0.0551R(V5)+0.0785S(V3)+ 0.2993T(V1))xQRS duration. The Sokolow-Lyon criterion reached the highest sensitivity (61%) and the R(aVL) voltage criterion reached the highest specificity (97%) when evaluated at their traditional partition value. However, at a fixed specificity of 95%, the sensitivity of these 10 criteria ranged from 16% to 32%. Best accuracy was obtained with the R(aVL) voltage criterion and the new composite time-voltage criterion (89% for both). Positive and negative predictive values varied considerably depending on the concomitant presence of 3 clinical risk factors for LVH (hypertension, age >/=50 years, overweight). Median positive and negative predictive values of the 10 ECG criteria were 15% and 95%, respectively, for subjects with none or 1 of these risk factors compared with 63% and 76% for subjects with all of them. In conclusion, the performance of classic ECG criteria for LVH detection was largely disparate and appeared to be lower in this population of East African origin than in white subjects. A newly generated composite time-voltage criterion might provide improved performance. The predictive value of ECG criteria for LVH was considerably enhanced with the integration of information on concomitant clinical risk factors for LVH.

Creació d’un visor web basat en software lliure per al Consorci d’Ardenya-Cadiretes

En aquest treball es pretén explicar el procés metodològic que s'ha seguit per a crear una eina informàtica de visualització de dades "online" per al Consorci d'Ardenya – Cadiretes. Inicialment s'explica el context en el que es desenvolupa el projecte, com a conveni de col·laboració en pràctiques, per a realitzar el treball de final del Màster en Tecnologies de la Informació Geogràfica, en la seva tretzena edició. S'explica també la situació de l'entitat col·laboradora del projecte, el consorci d'Ardenya – Cadiretes. Els objectius que es fixen al projecte són els de generar aquest visor amb eines de software lliure, de manera que el cost de producció sigui el menor possible. També es pretén crear una aplicació de senzill ús i que resulti atractiva per al client web. Es repassen els diferents aspectes tècnics i funcionals que ha de tenir en compte el projecte, per tal que aquest es pugui desenvolupar de forma correcte. Es tracten temes com el tipus de programari que s'ha de fer servir i per que unes aplicacions es consideren més oportunes que d'altres per a treballar tasques concretes del propi projecte. A través de la metodologia seguida en el projecte es repassa el dia a dia que s'ha anat seguint durant el projecte, des de l'inici en el que s'instal·laven els diferents programes necessaris fins al final de l'escriptura del codi de programació, passant per l'edició de les dades geogràfiques o la càrrega d'aquestes al servidor de mapes

A construção de um software educativo sobre ausculta dos sons respiratórios

O estudo objetivou relatar a experiência da construção de um software educativo sobre a ausculta dos sons respiratórios. Nesse processo, aplicou-se o referencial pedagógico de Lev Semenovic Vygotsky, e delimitou-se o conteúdo de modo a abarcar o método da ausculta passo a passo, as finalidades, a classificação dos sons normais e adventícios e as respectivas características estetoacústicas. Para o desenvolvimento do sistema, foi utilizada a tecnologia 3D, incluindo avatares (personificações virtuais do paciente, do enfermeiro e dos objetos) e ambiente virtual para a ausculta, usando procedimentos de simulação. Ao final do processo, concluiu-se que iniciativas dessa natureza, embora sejam permeadas de dificuldades, trazem contribuições importantes ao ensino-aprendizagem de conteúdos relativos à área da Enfermagem.

Propuesta para incorporar evaluación y pruebas de usabilidad dentro de un proceso de desarrollo de software

Usability is critical to consider an interactive software system successful. Usability testing and evaluation during product development have gained wide acceptance as a strategy to improve product quality. Early introduction of usability perspectives in a product is very important in order to provide a clear visibility of the quality aspects not only for the developers, but also for the testing users as well. However, usability evaluation and testing are not commonly taken into consideration as an essential element of the software development process. Then, this paper exposes a proposal to introduce usability evaluation and testing within a software development through reuse of software artifacts. Additionally, it suggests the introduction of an auditor within the classification of actors for usability tests. It also proposes an improvement of checklists used for heuristics evaluation, adding quantitative and qualitative aspects to them

Evaluation of melanoma vaccines with molecularly defined antigens by ex vivo monitoring of tumor-specific T cells.

Immunotherapy of melanoma is aimed to mobilize cytolytic CD8+ T cells playing a central role in protective immunity. Despite numerous clinical vaccine trials, only few patients exhibited strong antigen-specific T-cell activation, stressing the need to improve vaccine strategies. For a rational development, we propose to focus on molecularly defined vaccine components, and evaluate their immunogenicity with highly reproducible and standardized methods for ex vivo immune monitoring. Careful immunogenicity comparison of vaccine formulations in phase I/II studies allow to select optimized vaccines for subsequent clinical efficacy testing in large scale phase III trials.

Development of a well-defined medium for the in vitro maturation of immature bovine cumulus-oocyte complexes.

PURPOSE: Our purpose was to develop a well-defined medium for the in vitro maturation (IVM) of immature bovine cumulus-oocyte complexes (COC). METHODS: The COC were cultured in the presence of three protein supplementations: fetal bovine serum (FBS), bovine serum albumin, and Synthetic Serum Substitute. The embryos obtained after in vitro fertilization of IVM oocytes were cocultured with Vero cells and their development to the morula and blastocyst stages was studied. RESULTS: When FBS was absent from the IVM medium, a significantly lower fertilization rate was observed, followed by a decrease in the percentage of embryos reaching the blastocyst stage. When FBS was replaced by a defined protein supplementation, the best results were obtained with Synthetic Serum Substitute. CONCLUSIONS: Adequate protein supplementation of the IVM medium optimizes the fertilization rate and the development of bovine IVM oocytes. The implication of these results in the human field is discussed.

Implementació d'un contact center per empreses basat en software lliure

El proyecto consiste en la creación de un CRM de contact center con canal de telefonía y correo electrónico. Se ha llevado a cabo utilizando software libre. Se integra con centralita telefónica para permitir la realización de llamadas por Voip.