176 research outputs found
Zika virus infection and Guillain-Barré syndrome in three patients from Suriname
We present three patients from Suriname who were diagnosed with Guillain-Barré syndrome (GBS) during the Zika virus (ZIKV) outbreak in this country. One patient had a positive ZIKV urine real-time RT-PCR (qRT-PCR) result. The other two patients had a negative ZIKV urine qRT-PCR but a positive virus neutralization test and presence of IgG antibodies against ZIKV in the serum. Considering the evidence of a past ZIKV infection and absence of evidence for recent infections with the most common preceding infections of GBS, it is very likely that these GBS cases were triggered by ZIKV
Cytoskeletal mechanics of proplatelet maturation and platelet release
New steps in the process of conversion of proplatelet extensions from megakaryocytes into mature platelets are defined
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing
molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images
Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images
of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL
maps are derived through computational staining using a convolutional neural network trained to
classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and
correlation with overall survival. TIL map structural patterns were grouped using standard
histopathological parameters. These patterns are enriched in particular T cell subpopulations
derived from molecular measures. TIL densities and spatial structure were differentially enriched
among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial
infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic
patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for
the TCGA image archives with insights into the tumor-immune microenvironment
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
Directed Neural Differentiation of Mouse Embryonic Stem Cells Is a Sensitive System for the Identification of Novel Hox Gene Effectors
The evolutionarily conserved Hox family of homeodomain transcription factors
plays fundamental roles in regulating cell specification along the anterior
posterior axis during development of all bilaterian animals by controlling cell
fate choices in a highly localized, extracellular signal and cell context
dependent manner. Some studies have established downstream target genes in
specific systems but their identification is insufficient to explain either the
ability of Hox genes to direct homeotic transformations or the
breadth of their patterning potential. To begin delineating Hox
gene function in neural development we used a mouse ES cell based system that
combines efficient neural differentiation with inducible Hoxb1 expression. Gene
expression profiling suggested that Hoxb1 acted as both
activator and repressor in the short term but predominantly as a repressor in
the long run. Activated and repressed genes segregated in distinct processes
suggesting that, in the context examined, Hoxb1 blocked
differentiation while activating genes related to early developmental processes,
wnt and cell surface receptor linked signal transduction and cell-to-cell
communication. To further elucidate aspects of Hoxb1 function
we used loss and gain of function approaches in the mouse and chick embryos. We
show that Hoxb1 acts as an activator to establish the full expression domain of
CRABPI and II in rhombomere 4 and as a
repressor to restrict expression of Lhx5 and
Lhx9. Thus the Hoxb1 patterning activity
includes the regulation of the cellular response to retinoic acid and the delay
of the expression of genes that commit cells to neural differentiation. The
results of this study show that ES neural differentiation and inducible
Hox gene expression can be used as a sensitive model system
to systematically identify Hox novel target genes, delineate
their interactions with signaling pathways in dictating cell fate and define the
extent of functional overlap among different Hox genes
The chemistry of sulfur and nitrogen species in a fog system A multiphase approach
Concentration and phase distribution of sulfur and nitrogen species during a particular fog episode in the Po Valley are experimentally described in this paper. Chemical measurements were carried out simultaneously at different heights within the fog layer, up to 50 m. Microphysical and meteorological parameters necessary for the description of the fog multiphase system were also concurrently measured as a function of height. The fog cycle (formation, evolution, dissipation) is described in terms of the total acidity of a unit volume of air containing gas species, interstitial aerosol particles and fog droplets. The fog system was not closed and input of acidic and basic components was observed during fog evolution. The driving force which determines the acidity of the fog multiphase atmospheric system was found to be the presence of NH 3 and its partitioning among the different phases. A strong decrease of fog water pH (from 5.6 down to 2.8) was observed during fog evolution and was attributed to a HNO 3 input to the system. These acidic and basic inputs are described in terms of a titration/back-titration process of the fog system. The SO 2 oxidation process in fog water was found to be of minor importance in determining the SO 4 = concentration within the fog system, due to both low SO 2 concentration and limited oxidant availability during the experiment. DOI: 10.1034/j.1600-0889.1992.t01-4-00005.
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Physics Basis for the Advanced Tokamak Fusion Power Plant ARIES-AT
The advanced tokamak is considered as the basis for a fusion power plant. The ARIES-AT design has an aspect ratio of A always equal to R/a = 4.0, an elongation and triangularity of kappa = 2.20, delta = 0.90 (evaluated at the separatrix surface), a toroidal beta of beta = 9.1% (normalized to the vacuum toroidal field at the plasma center), which corresponds to a normalized beta of bN * 100 x b/(I(sub)P(MA)/a(m)B(T)) = 5.4. These beta values are chosen to be 10% below the ideal-MHD stability limit. The bootstrap-current fraction is fBS * I(sub)BS/I(sub)P = 0.91. This leads to a design with total plasma current I(sub)P = 12.8 MA, and toroidal field of 11.1 T (at the coil edge) and 5.8 T (at the plasma center). The major and minor radii are 5.2 and 1.3 m, respectively. The effects of H-mode edge gradients and the stability of this configuration to non-ideal modes is analyzed. The current-drive system consists of ICRF/FW for on-axis current drive and a lower-hybrid system for off-axis. Tran sport projections are presented using the drift-wave based GLF23 model. The approach to power and particle exhaust using both plasma core and scrape-off-layer radiation is presented
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