Protein-mediated RNA folding governs sequence-specific interactions between rotavirus genome segments

Segmented RNA viruses are ubiquitous pathogens, which include influenza viruses and rotaviruses. A major challenge in understanding their assembly is the combinatorial problem of a non-random selection of a full genomic set of distinct RNAs. This process involves complex protein/RNA interactions, which are often obscured by non-specific binding at concentrations approaching in vvo assembly conditions. Here, we present direct experimental evidence of sequence-specific inter-segment interactions in rotaviruses, taking place in a complex RNA- and protein- rich milieu. We show that binding of the rotaviral protein NSP2 to ssRNAs results in the remodeling of RNA, which is conducive to formation of inter-segment contacts. To identify the sites of these interactions, we have developed an RNA-RNA SELEX approach for mapping the sequences involved in inter-segment base-pairing. Our findings elucidate the molecular basis underlying inter-segment interactions in rotaviruses, paving the way for delineating RNA-RNA interactions that govern assembly of other segmented RNA viruse

Hoop/column antenna RF verification model. Volume 2: Analysis and correlation

As part of the Large Space System Technology Program, the theoretical and experimental results of the RF characteristic of a hoop/column, quad aperture antenna using an RF verification model are presented. To satisfy the primary purposes of the model, experimental pattern data is provided for the quad aperture configuration at different reflector edge illumination levels, from which the geometry and edge effects can be assessed, and experimental data which can be compared with calculations using various theoretical reflector scattering formulae are provided. It also experimentally determines the effects upon secondary patterns of scale model quartz cables, as used in the hoop/column design, upon secondary patterns in order to assess the importance of developing a scattering theory to predict such effects. In addition, a comprehensive theoretical study and the experimental pattern results of quad aperture antenna feeds, a discussion of the fundamental affect of parasitic side lobes, their amplitude, and location in space

Hoop/Column Antenna: RF Verification Model. Volume 1: Test Results

As part of the Large Space System Technology Program, this report, in two volumes, presents the theoretical and experimental results of the RF characteristic of a hoop/column, quad aperture antenna using an RF verification model. To satisfy the primary purposes of the model it provides experimental pattern data for the quad aperture configuration at different reflector edge illumination levels, from which the geometry and edge effects can be assessed, and provides experimental data which can be compared with calculations using various theoretical reflector scattering formulae. It also experimentally determines the effects upon secondary patterns of scale model quartz cables, as used in the hoop/column design, upon secondary patterns in order to assess the importance of developing a scattering theory to predict such effects. In addition, this report contains a comprehensive theoretical study and the experimental pattern results of quad aperture antenna feeds, a discussion of the fundamental affect of parasitic side lobes, their amplitude, and location in space

SYSTEMS ENGINEERING AND ASSURANCE MODELING (SEAM): A WEB-BASED SOLUTION FOR INTEGRATED MISSION ASSURANCE

We present an overview of the Systems Engineering and Assurance Modeling (SEAM) platform, a web-browser-based tool which is designed to help engineers evaluate the radiation vulnerabilities and develop an assurance approach for electronic parts in space systems. The SEAM framework consists of three interconnected modeling tools, a SysML compatible system description tool, a Goal Structuring Notation (GSN) visual argument tool, and Bayesian Net and Fault Tree extraction and export tools. The SysML and GSN sections also have a coverage check application that ensures that every radiation fault identified on the SysML side is also addressed in the assurance case in GSN. The SEAM platform works on space systems of any degree of radiation hardness but is especially helpful for assessing radiation performance in systems with commercial-off-the-shelf (COTS) electronic components

Default Risk and Equity Returns: A Comparison of the Bank-Based German and the U.S. Financial System

In this paper, we address the question whether the impact of default risk on equity returns depends on the financial system firms operate in. Using an implementation of Merton's option-pricing model for the value of equity to estimate firms' default risk, we construct a factor that measures the excess return of firms with low default risk over firms with high default risk. We then compare results from asset pricing tests for the German and the U.S. stock markets. Since Germany is the prime example of a bank-based financial system, where debt is supposedly a major instrument of corporate governance, we expect that a systematic default risk effect on equity returns should be more pronounced for German rather than U.S. firms. Our evidence suggests that a higher firm default risk systematically leads to lower returns in both capital markets. This contradicts some previous results for the U.S. by Vassalou/Xing (2004), but we show that their default risk factor looses its explanatory power if one includes a default risk factor measured as a factor mimicking portfolio. It further turns out that the composition of corporate debt affects equity returns in Germany. Firms' default risk sensitivities are attenuated the more a firm depends on bank debt financing

Characterizing SRAM Single Event Upset in Terms of Single and Double Node Charge Collection

A well-collapse source-injection mode for SRAM SEU is demonstrated through TCAD modeling. The recovery of the SRAM s state is shown to be based upon the resistive path from the p+-sources in the SRAM to the well. Multiple cell upset patterns for direct charge collection and the well-collapse source-injection mechanisms are then predicted and compared to recent SRAM test data

Methods and strategies for gene structure curation in WormBase

The Caenorhabditis elegans genome sequence was published over a decade ago; this was the first published genome of a multi-cellular organism and now the WormBase project has had a decade of experience in curating this genome's sequence and gene structures. In one of its roles as a central repository for nematode biology, WormBase continues to refine the gene structure annotations using sequence similarity and other computational methods, as well as information from the literature- and community-submitted annotations. We describe the various methods of gene structure curation that have been tried by WormBase and the problems associated with each of them. We also describe the current strategy for gene structure curation, and introduce the WormBase ‘curation tool’, which integrates different data sources in order to identify new and correct gene structures

Histone 3.3 hotspot mutations in conventional osteosarcomas: a comprehensive clinical and molecular characterization of six H3F3A mutated cases

Background: Histone 3.3 (H3.3) hotspot mutations in bone tumors occur in the vast majority of giant cell tumors of bone (GCTBs; 96%), chondroblastomas (95%) and in a few cases of osteosarcomas. However, clinical presentation, histopathological features, and additional molecular characteristics of H3.3 mutant osteosarcomas are largely unknown. Methods: In this multicentre, retrospective study, a total of 106 conventional high-grade osteosarcomas, across all age groups were re-examined for hotspot mutations in the H3.3 coding genes H3F3A and H3F3B. H3.3 mutant osteosarcomas were re-evaluated in a multidisciplinary manner and analyzed for genome-wide DNA-methylation patterns and DNA copy number aberrations alongside H3.3 wild-type osteosarcomas and H3F3A G34W/L mutant GCTBs. Results: Six osteosarcomas (6/106) carried H3F3A hotspot mutations. No mutations were found in H3F3B. All patients with H3F3A mutant osteosarcoma were older than 30 years with a median age of 65 years. Copy number aberrations that are commonly encountered in high-grade osteosarcomas also occurred in H3F3A mutant osteosarcomas. Unlike a single osteosarcoma with a H3F3A K27M mutation, the DNA methylation profiles of H3F3A G34W/R mutant osteosarcomas were clearly different from H3.3 wild-type osteosarcomas, but more closely related to GCTBs. The most differentially methylated promoters between H3F3A G34W/R mutant and H3.3 wild-type osteosarcomas were in KLLN/PTEN (p < 0.00005) and HIST1H2BB (p < 0.0005). Conclusions: H3.3 mutations in osteosarcomas may occur in H3F3A at mutational hotspots. They are overall rare, but become more frequent in osteosarcoma patients older than 30 years. Osteosarcomas carrying H3F3A G34W/R mutations are associated with epigenetic dysregulation of KLLN/PTEN and HIST1H2BB