Microstructure and Velocity of Field-Driven SOS Interfaces: Analytic Approximations and Numerical Results

The local structure of a solid-on-solid (SOS) interface in a two-dimensional kinetic Ising ferromagnet with single-spin-flip Glauber dynamics, which is driven far from equilibrium by an applied field, is studied by an analytic mean-field, nonlinear-response theory [P.A. Rikvold and M. Kolesik, J. Stat. Phys. 100, 377 (2000)] and by dynamic Monte Carlo simulations. The probability density of the height of an individual step in the surface is obtained, both analytically and by simulation. The width of the probability density is found to increase dramatically with the magnitude of the applied field, with close agreement between the theoretical predictions and the simulation results. Excellent agreement between theory and simulations is also found for the field-dependence and anisotropy of the interface velocity. The joint distribution of nearest-neighbor step heights is obtained by simulation. It shows increasing correlations with increasing field, similar to the skewness observed in other examples of growing surfaces.Comment: 18 pages RevTex4 with imbedded figure

High-speed 1.55 μm operation of low-temperature-grown GaAs-based resonant-cavity-enhanced p-i-n photodiodes

The 1.55 μm high-speed operation of GaAs-based p-i-n photodiodes was demonstrated and their design, growth and fabrication were discussed. A resonant-cavity-detector structure was used to selectively enhance the photoresponse at 1.55 μm. The bottom mirror of the resonant cavity was formed by a highly reflecting 15-pair GaAs/AlAs Bragg mirror and molecular-beam epitaxy was used for wafer growth. It was found that the fabricated devices exhibited a resonance of around 1548 nm and an enhancement factor of 7.5 was achieved when compared to the efficiency of a single-pass detector

Estudos sorológicos para pesquisa de anticorpos de arbovírus em população humana da região do Vale do Ribeira: III - inquérito em coabitantes com casos de encefalite por Flavivirus Rocio

A serological survey for hemagglutination-inhibition antibodies to 17 arbovirus was carried out in households with cases of Rocio encephalitis, in the urban zone of four cities of the Ribeira Valley, Brazil, where an epidemic of Rocio encephalitis occurred recently. Among those households the prevalence of Rocio antibodies was not higher than in households without cases of encephalitis. Some facts, which were reported before, were again observed: a large prevalence of antibodies in men, particulary fishermen, an increase of antibodies with age and the presence of one past case of encephalitis that presented only neutralizing antibodies against EEE. That Alphavirus has never been responsible for human disease in the area. There is also a very small proportion of people with Rocio and Flavivirus antibodies which, in view of the recent epidemic, was surprising.Foi realizado inquérito sorológico para pesquisa de anticorpos de 17 arbovírus existentes no país, em coabitantes com doentes de encefalite por Rocio, residentes em zona urbana da região do Vale do Ribeira, São Paulo (Brasil), onde ocorreu recentemente uma extensa epidemia dessa moléstia. Não se verificou maior prevalência de anticorpos IH para vírus Rocio nessas pessoas quando comparadas com indivíduos que não coabitavam com doentes de encefalite. Foram observados e discutidos alguns aspectos já verificados em outros grupos populacionais estudados anteriormente: maior prevalência de anticorpos IH de arbovírus em homens, particularmente pescadores; aumento dessa prevalência com a idade e presença de pessoa com antecedente de encefalite que apresentou, exclusivamente anticorpos neutralizantes para o Alphavirus EEL, o qual até agora não tem sido responsabilizado por moléstia na região. Encontrou-se baixa proporção de indivíduos com anticorpos para Rocio e Flavivirus em geral, fato este estranhável considerando a recente epidemia

Pre-clinical evaluation of a quadrivalent HCV VLP vaccine in pigs following microneedle delivery

The introduction of directly acting antiviral agents (DAAs) has produced significant improvements in the ability to cure chronic hepatitis C infection. However, with over 2% of the world's population infected with HCV, complications arising from the development of cirrhosis of the liver, chronic hepatitis C infection remains the leading indication for liver transplantation. Several modelling studies have indicated that DAAs alone will not be sufficient to eliminate HCV, but if combined with an effective vaccine this regimen would provide a significant advance towards achieving this critical World Health Organisation goal. We have previously generated a genotype 1a, 1b, 2a, 3a HCV virus like particle (VLP) quadrivalent vaccine. The HCV VLPs contain the core and envelope proteins (E1 and E2) of HCV and the vaccine has been shown to produce broad humoral and T cell immune responses following vaccination of mice. In this report we further advanced this work by investigating vaccine responses in a large animal model. We demonstrate that intradermal microneedle vaccination of pigs with our quadrivalent HCV VLP based vaccine produces long-lived multi-genotype specific and neutralizing antibody (NAb) responses together with strong T cell and granzyme B responses and normal Th1 and Th2 cytokine responses. These responses were achieved without the addition of adjuvant. Our study demonstrates that our vaccine is able to produce broad immune responses in a large animal that, next to primates, is the closest animal model to humans. Our results are important as they show that the vaccine can produce robust immune responses in a large animal model before progressing the vaccine to human trials.D. Christiansen, L. Earnest-Silveira, B. Grubor-Bauk, D. K. Wijesundara, I. Boo, P. A. Ramsland, E. Vincan, H. E. Drummer, E. J. Gowans and J. Torres

Global assessment of dengue Virus-Specific CD4+ T cell responses in Dengue-Endemic areas

Background: Dengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV). To enable global assessment of CD4+ T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4+ T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua. Methods: HLA class II epitopes in the population of Managua were identified by an in vitro IFNγ ELISPOT assay. CD4+ T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen-presenting cells, followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a “megapool” (MP) consisting of 180 peptides specifically designed to achieve balanced HLA and DENV serotype coverage. The DENV CD4MP180 was validated by intracellular cytokine staining assays. Results: We detected responses directed against a total of 431 epitopes, representing all 4 DENV serotypes, restricted by 15 different HLA-DRB1 alleles. The responses were associated with a similar pattern of protein immunodominance, overall higher magnitude of responses, as compared to what was observed previously in the Sri Lanka region. Based on these epitope mapping studies, we designed a DENV CD4 MP180 with higher and more consistent coverage, which allowed the detection of CD4+ T cell DENV responses ex vivo in various cohorts of DENV exposed donors worldwide, including donors from Nicaragua, Brazil, Singapore, Sri Lanka, and U.S. domestic flavivirus-naïve subjects immunized with Tetravalent Dengue Live-Attenuated Vaccine (TV005). This broad reactivity reflects that the 21 HLA-DRB1 alleles analyzed in this and previous studies account for more than 80% of alleles present with a phenotypic frequency ≥5% worldwide, corresponding to 92% phenotypic coverage of the general population (i.e., 92% of individuals express at least one of these alleles). Conclusion: The DENV CD4 MP180 can be utilized to measure ex vivo responses to DENV irrespective of geographical location

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types