98 research outputs found
Application of a floating well concept to a latch-up-free, low-cost, smart power high-side switch technology
The aim of this brief is to present an original design methodology that permits implementing latch-up-free smart power circuits on a very simple, cost-effective technology. The basic concept used for this purpose is letting float the wells of the MOS transistors most susceptible to initiate latch-up
Application of a floating well concept to a latch-up-free, low-cost, smart power high-side switch technology
Lipid Anti-Lipid Antibody Responses Correlate with Disease Activity in Systemic Lupus Erythematosus
10.1371/journal.pone.0055639PLoS ONE82
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
MHC Class I Endosomal and Lysosomal Trafficking Coincides with Exogenous Antigen Loading in Dendritic Cells
BACKGROUND: Cross-presentation by dendritic cells (DCs) is a crucial prerequisite for effective priming of cytotoxic T-cell responses against bacterial, viral and tumor antigens; however, this antigen presentation pathway remains poorly defined. METHODOLOGY/PRINCIPAL FINDINGS: In order to develop a comprehensive understanding of this process, we tested the hypothesis that the internalization of MHC class I molecules (MHC-I) from the cell surface is directly involved in cross-presentation pathway and the loading of antigenic peptides. Here we provide the first examination of the internalization of MHC-I in DCs and we demonstrate that the cytoplasmic domain of MHC-I appears to act as an addressin domain to route MHC-I to both endosomal and lysosomal compartments of DCs, where it is demonstrated that loading of peptides derived from exogenously-derived proteins occurs. Furthermore, by chasing MHC-I from the cell surface of normal and transgenic DCs expressing mutant forms of MHC-I, we observe that a tyrosine-based endocytic trafficking motif is required for the constitutive internalization of MHC-I molecules from the cell surface into early endosomes and subsequently deep into lysosomal peptide-loading compartments. Finally, our data support the concept that multiple pathways of peptide loading of cross-presented antigens may exist depending on the chemical nature and size of the antigen requiring processing. CONCLUSIONS/SIGNIFICANCE: We conclude that DCs have 'hijacked' and adapted a common vacuolar/endocytic intracellular trafficking pathway to facilitate MHC I access to the endosomal and lysosomal compartments where antigen processing and loading and antigen cross-presentation takes place
A human PrM antibody that recognizes a novel cryptic epitope on dengue E glycoprotein
10.1371/journal.pone.0033451PLoS ONE74
Southern Ocean cloud and aerosol data: a compilation of measurements from the 2018 Southern Ocean Ross Sea Marine Ecosystems and Environment voyage
Due to its remote location and extreme weather conditions, atmospheric in situ
measurements are rare in the Southern Ocean. As a result, aerosol–cloud
interactions in this region are poorly understood and remain a major source of
uncertainty in climate models. This, in turn, contributes substantially to
persistent biases in climate model simulations such as the well-known positive
shortwave radiation bias at the surface, as well as biases in numerical
weather prediction models and reanalyses. It has been shown in previous
studies that in situ and ground-based remote sensing measurements across the
Southern Ocean are critical for complementing satellite data sets due to the
importance of boundary layer and low-level cloud processes. These processes
are poorly sampled by satellite-based measurements and are often obscured by
multiple overlying cloud layers. Satellite measurements also do not constrain
the aerosol–cloud processes very well with imprecise estimation of cloud
condensation nuclei. In this work, we present a comprehensive set of ship-based
aerosol and meteorological observations collected on the 6-week
Southern Ocean Ross Sea Marine Ecosystem and Environment voyage
(TAN1802) voyage of RV Tangaroa across the Southern Ocean, from Wellington, New Zealand, to
the Ross Sea, Antarctica. The voyage was carried out from 8 February to
21 March 2018. Many distinct, but contemporaneous, data sets were collected
throughout the voyage. The compiled data sets include measurements from a
range of instruments, such as (i) meteorological conditions at the sea surface
and profile measurements; (ii) the size and concentration of particles; (iii)
trace gases dissolved in the ocean surface such as dimethyl sulfide and
carbonyl sulfide; (iv) and remotely sensed observations of low clouds. Here,
we describe the voyage, the instruments, and data processing, and provide a brief
overview of some of the data products available. We encourage the scientific
community to use these measurements for further analysis and model evaluation
studies, in particular, for studies of Southern Ocean clouds, aerosol, and
their interaction. The data sets presented in this study are publicly
available at https://doi.org/10.5281/zenodo.4060237 (Kremser et al., 2020)
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