Overview Of Coupling Of Data, Models And Information Through The Web Using Existing Standards

Assessment of environmental status and integral safety requires combination of information from many sources, coming from either databases or increasingly via live model (scenario) simulations. Many of these models require input from one another, sometimes unidirectional, but more and more two-directional as well. Many protocols and frameworks are available for model coupling, often based on open standards and implementations. Previous overviews of coupling protocols have focused on data exchange volume, data complexity, invasiveness into existing models and support for specific programming languages. We extend the overview using recent developments in web-based protocols and focus on the suitability for internet-based data exchange. We also extend the focus of previous reviews by also taking the coupling with aggregated information products for end-users into account. We propose a hierarchical ordering of all standards for specific types of end-users

Susceptibility of Thymocytes for Infection by Chicken Anemia Virus is Related to Pre- and Posthatching Development

To investigate the age-dependent mechanism of susceptibility for chicken anemia virus (CAV) infection, we inoculated embryos and chickens of ages between day 9 of embryonic development and day 28 after hatching with CAV. Chicken embryos inoculated at days 9 and 11 of development showed no CAV-infected cells in the thymus, nor in other lymphoid organs. Many CAV-infected cells were detected in the thymic cortex of all chicken embryos inoculated at days 13 and 16 of development and of all chickens inoculated 1, 3, and 7 days after hatching. All embryos and chickens that contained CAV-infected cells in the thymus also contained CAV-infected cells in the bone marrow, but not in the bursa of Fabricius or the spleen. In chickens inoculated at days 14 and 21, only few CAV-infected cells were detected in the thymus, whereas these cells were not detected in thymi of 28-day-old inoculated chickens. Depletion of the thymic cortex was only detected in chickens inoculated from day 16 of embryonic development till day 21 after hatching. Only hematocrit values of the chickens inoculated 1 and 3 days after hatching were below normal. The rationale for the simultaneous susceptibility of cells of the T-cell lineage and cells of the erythrocyte lineage is discussed. As far as the thymus is concerned, the absence of clinical and microscopical signs of CAV infection in older chickens and the inability of CAV to infect embryos at days 9 and 11 of embryonic development may be caused by a lack of susceptible thymocytes. In view of the three waves of thymic precursor cells that populate the thymus during ontogeny, as described by Le Douarin and colleagues, we hypothesize that CAV only infects thymocytes derived from the second wave of precursor cells

Generalized Toda Theory from Six Dimensions and the Conifold

Recently, a physical derivation of the Alday-Gaiotto-Tachikawa correspondence has been put forward. A crucial role is played by the complex Chern-Simons theory arising in the 3d-3d correspondence, whose boundary modes lead to Toda theory on a Riemann surface. We explore several features of this derivation and subsequently argue that it can be extended to a generalization of the AGT correspondence. The latter involves codimension two defects in six dimensions that wrap the Riemann surface. We use a purely geometrical description of these defects and find that the generalized AGT setup can be modeled in a pole region using generalized conifolds. Furthermore, we argue that the ordinary conifold clarifies several features of the derivation of the original AGT correspondence.Comment: 27+2 pages, 3 figure

Correction to: Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases

In the original publication of the article, consortium author list was missing in the article

Correction to: Solving patients with rare diseases through programmatic reanalysis of genome-phenome data

In the original publication of the article, consortium author lists were missing in the articl

Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases.

For the first time in Europe hundreds of rare disease (RD) experts team up to actively share and jointly analyse existing patient's data. Solve-RD is a Horizon 2020-supported EU flagship project bringing together >300 clinicians, scientists, and patient representatives of 51 sites from 15 countries. Solve-RD is built upon a core group of four European Reference Networks (ERNs; ERN-ITHACA, ERN-RND, ERN-Euro NMD, ERN-GENTURIS) which annually see more than 270,000 RD patients with respective pathologies. The main ambition is to solve unsolved rare diseases for which a molecular cause is not yet known. This is achieved through an innovative clinical research environment that introduces novel ways to organise expertise and data. Two major approaches are being pursued (i) massive data re-analysis of >19,000 unsolved rare disease patients and (ii) novel combined -omics approaches. The minimum requirement to be eligible for the analysis activities is an inconclusive exome that can be shared with controlled access. The first preliminary data re-analysis has already diagnosed 255 cases form 8393 exomes/genome datasets. This unprecedented degree of collaboration focused on sharing of data and expertise shall identify many new disease genes and enable diagnosis of many so far undiagnosed patients from all over Europe

Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques

Solving unsolved rare neurological diseases-a Solve-RD viewpoint.

Funder: Durch Princess Beatrix Muscle Fund Durch Speeren voor Spieren Muscle FundFunder: University of Tübingen Medical Faculty PATE programFunder: European Reference Network for Rare Neurological Diseases | 739510Funder: European Joint Program on Rare Diseases (EJP-RD COFUND-EJP) | 44140962