80 research outputs found

    Applications of genetic algorithms in bioinformatics

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    Spatial Distribution of Volcanic Hotspots and Paterae on Io: Implications for Tidal Heating Models and Magmatic Pathways

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    Io, the innermost of Jupiter's Galilean satellites, is the most volcanically active body in the Solar. System. Io's global mean heat flow is approximately 2 W/square m, which is approximately 20 times larger than on Earth. High surface temperatures concentrate within "hotspots" and, to date, 172 Ionian hotspots have been identified by spacecraft and Earth-based telescopes. The Laplace resonance between Io, Europa, and Ganymede maintains these satellites in noncircular orbits and causes displacement of their tidal bulges as the overhead position of Jupiter changes for each moon. Gravitational interactions between Jupiter and Io dominate the orbital evolution of the Laplacian system and generate enormous heat within to as tidal energy is dissipated. If this energy were transferred out of Io at the same rate as it is generated, then the associated surface heat flux would be 2.24 +/- 0.45 W/square m. This estimate is in good agreement with observed global heat flow, but to better constrain tidal dissipation mechanisms and infer how thermal energy is transferred to Io's surface, it is critical to closely examine the spatial distribution of volcanic features. End-member tidal dissipation models either consider that heating occurs completely in the mantle, or completely in the asthenosphere. Mixed models typically favor one-third mantle and two-thirds asthenosphere heating. Recent models also consider the effects of mantle-asthenosphere boundary permeability and asthenospheric instabilities. Deep-mantle heating models predict maximum surface heat flux near the poles, whereas asthenosphere heating models predict maxima near the equator-particularly in the Sub-Jovian and Anti-Jovian hemispheres, with smaller maxima occurring at orbit tangent longitudes. Previous studies have examined the global distribution of Ionian hotspots and patera (i.e., irregular or complex craters with scalloped edges that are generally interpreted to be volcanic calderas), but in this study, we combine a new geospatial analysis technique with an improved hotspot and paterae database

    A Comparison Of Mississippian (320 Million Years Ago) And Modern Analogous Marine Assemblages

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    This investigation studies the similarities and differences in guild structure, species diversity, and depositional environment between two assemblages, one a member of the Late Paleozoic Fauna (Mississippian age) and the other from the Modern Fauna

    Random Matrix Model for Superconductors in a Magnetic Field

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    We introduce a random matrix ensemble for bulk type-II superconductors in the mixed state and determine the single-particle excitation spectrum using random matrix theory. The results are compared with planar tunnel junction experiments in PbBi thin films. More low energy states appear than in the Abrikosov-Gor'kov-Maki or Ginzburg-Landau descriptions, consistent with observations.Comment: 4 pages, 1 postscript figure, to appear in Phys. Rev. Let

    Concordance of Aqueous Humor Flow in the Morning and at Night in Normal Humans

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    PURPOSE. To test the hypothesis that an individual shows concordance of aqueous humor flow in the morning and at night in a prospective inpatient fluorophotometry study in healthy subjects. METHODS. Flow was measured in each eye every hour between 8 AM and noon and every 2 hours between midnight and 6 AM. Morning and nighttime flows were analyzed for differences between eyes and for differences between these two time points. Concordance of individual morning and nighttime flows were studied by categorization into low, medium, or high tertiles, dot plot, and ordinary least-squares regression (OLS) scatter plot. RESULTS. In 28 subjects, the flow was similar between eyes within a subject with healthy eyes. In the one eye examined in each subject, the average flow was 3.12 Ï® 1.09 L/min in the morning, which decreased significantly to 1.59 Ï® 0.58 L/min at night. During each time period, the individual flow data were normally distributed. Concordance of an individual's morning and nighttime flows was 68%. A scatter plot of morning versus nighttime flows also supported concordance with an OLS regression fit of r 2 Ï­ 0.45. CONCLUSIONS. The results provide evidence that aqueous humor flow is similar between eyes, that flow variation shows a normal distribution, and that individuals show a concordance of flow in the morning and at night. These observations support the posit that aqueous humor flow, which is a factor that contributes to the important clinical risk factor of IOP variation, is amenable to study as a quantitative trait. (Invest Ophthalmol Vis Sci. 2006;47: 4860 -4864

    Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

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    Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes

    Integrated Molecular Characterization of Uterine Carcinosarcoma

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    SummaryWe performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified

    Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

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    Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance

    Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

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    Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

    Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

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    SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers
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