Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes

Cytotoxic T lymphocytes (CTL) protect against viruses including HIV-1. To avoid viral escape mutants that thwart immunity, we chose 25 CTL epitopes defined in the context of natural infection with functional and/or structural constraints that maintain sequence conservation. By combining HLA binding predictions with knowledge concerning HLA allele frequencies, a metric estimating population protection coverage (PPC) was computed and epitope pools assembled. Strikingly, only a minority of immunocompetent HIV-1 infected individuals responds to pools with PPC >95%. In contrast, virus-naive individuals uniformly expand IFNγ producing cells and mount anti-HIV-1 cytolytic activity. This disparity suggests a vaccine design paradigm shift from infected to normal subjects

The T2K ND280 Off-Axis Pi-Zero Detector

The Pi-Zero detector (P{\O}D) is one of the subdetectors that makes up the off-axis near detector for the Tokai-to-Kamioka (T2K) long baseline neutrino experiment. The primary goal for the P{\O}D is to measure the relevant cross sections for neutrino interactions that generate pi-zero's, especially the cross section for neutral current pi-zero interactions, which are one of the dominant sources of background to the electron neutrino appearance signal in T2K. The P{\O}D is composed of layers of plastic scintillator alternating with water bags and brass sheets or lead sheets and is one of the first detectors to use Multi-Pixel Photon Counters (MPPCs) on a large scale.Comment: 17 pages, submitted to NIM

Prevalência de depressão e fatores associados em homens

El objetivo del presente estudio fue evaluar la prevalencia de depresión, detectar el riesgo suicida e identificar los factores sociodemográficos y personales asociados a este trastorno. La muestra no aleatorizada estuvo conformada por 1525 hombres colombianos con edades entre 18 y 83 años procedentes de 22 departamentos y de distintos niveles educativos. Para evaluar la depresión se usó el Cuestionario de Depresión para Hombres (Álvarez y Londoño, 2012); para evaluar la comorbilidad con ansiedad se usó la Escala de Ansiedad HADS (Zigmond y Snaith, 1983) y el IMAFE (Lara, 1991); y para recolectar información acerca de los factores personales y sociodemográficos se usó una ficha de registro. Se analizaron los datos para calcular la prevalencia de corte, el riesgo suicida, la comorbilidad a través del uso del paquete estadístico SPSS. Se concluye que la prevalencia real reportada y el riesgo suicida en la población estudiada son más altos que los detectados usando un instrumento no sensible al género.O objetivo deste estudo foi avaliar a prevalência de depressão, detectar o risco suicida e identificar os fatores sociodemográficos e pessoais associados com esse transtorno. A amostra não aleatorizada foi conformada por 1525 homens colombianos com idade entre 18 e 83 anos, procedentes de 22 estados e de diferentes níveis de escolaridade. Para avaliar a depressão, foi utilizado o Teste de Depressão para Homens (Álvarez e Londoño, 2012); para avaliar a comorbilidade com ansiedade, usou-se a Escala Hospitalar de Ansiedade e Depressão (Hads – Zigmond e Snaith, 1983) e o Inventário de Masculinidade e Feminilidade (Imafe – Lara, 1991); para coletar informação sobre os fatores pessoais e sociodemográficos, empregou-se um formulário de registro. Analisaram-se os dados para calcular a prevalência de corte, o risco suicida, a comorbilidade por meio do uso do SPSS. Concluise que a prevalência real relatada e o risco de suicídio na população estudada são mais altos do que os detectados usando um instrumento não sensível ao gênero.This epidemiologic study aimed to evaluate the prevalence of depression, the suicide risk and the demographic and personal factors associated with depression severity in men. The non-randomized sample of participants was formed by 1525 Colombian men aged 18 to 83 years old, from 22 departments and different educational levels. The instruments used to evaluate the above factors were the Men’s Depression Questionnaire (Alvarez and Londoño, 2012), the Anxiety Scale HADS (Zigmond y Snaith, 1983) and the IMAFE (Lara 1991), and in order to collect data about personal and socio-demographic factors, a registration card was used. Data were analyzed to calculate the prevalence, suicide risk and comorbidity with anxiety through the use of SPSS. It was concluded that the prevalence of depression and suicide risk in the population object of study is higher than the one identified in previous studies when a non- gender sensitive questionnaire was used

PVS: a web server for protein sequence variability analysis tuned to facilitate conserved epitope discovery

We have developed PVS (Protein Variability Server), a web-based tool that uses several variability metrics to compute the absolute site variability in multiple protein-sequence alignments (MSAs). The variability is then assigned to a user-selected reference sequence consisting of either the first sequence in the alignment or a consensus sequence. Subsequently, PVS performs tasks that are relevant for structure-function studies, such as plotting and visualizing the variability in a relevant 3D-structure. Neatly, PVS also implements some other tasks that are thought to facilitate the design of epitope discovery-driven vaccines against pathogens where sequence variability largely contributes to immune evasion. Thus, PVS can return the conserved fragments in the MSA—as defined by a user-provided variability threshold—and locate them in a relevant 3D-structure. Furthermore, PVS can return a variability-masked sequence, which can be directly submitted to the RANKPEP server for the prediction of conserved T-cell epitopes. PVS is freely available at: http://imed.med.ucm.es/PVS/