Click Chemistry A unified click chemistry approach, termed diversity‐oriented clicking, is introduced by J. E. Moses et al. in their Research Article on page 12460 for the synthesis of diverse ...lead‐like structures.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Human gammaherpesviruses are associated with malignancies in HIV infected individuals; in macaques used in non-human primate models of HIV infection, gammaherpesvirus infections also occur. Limited ...data on prevalence and tumorigenicity of macaque gammaherpesviruses, mostly cross-sectional analyses of small series, are available. We comprehensively examine all three-rhesus macaque gammaherpesviruses -Rhesus rhadinovirus (RRV), Rhesus Lymphocryptovirus (RLCV) and Retroperitoneal Fibromatosis Herpesvirus (RFHV) in macaques experimentally infected with Simian Immunodeficiency Virus or Simian Human Immunodeficiency Virus (SIV/SHIV) in studies spanning 15 years at the AIDS and Cancer Virus Program of the Frederick National Laboratory for Cancer Research. We evaluated 18 animals with malignancies (16 lymphomas, one fibrosarcoma and one carcinoma) and 32 controls. We developed real time quantitative PCR assays for each gammaherpesvirus DNA viral load (VL) in malignant and non-tumor tissues; we also characterized the tumors using immunohistochemistry and in situ hybridization. Furthermore, we retrospectively quantified gammaherpesvirus DNA VL and SIV/SHIV RNA VL in longitudinally-collected PBMCs and plasma, respectively. One or more gammaherpesviruses were detected in 17 tumors; generally, one was predominant, and the relevant DNA VL in the tumor was very high compared to surrounding tissues. RLCV was predominant in tumors resembling diffuse large B cell lymphomas; in a Burkitt-like lymphoma, RRV was predominant; and in the fibrosarcoma, RFHV was predominant. Median RRV and RLCV PBMC DNA VL were significantly higher in cases than controls; SIV/SHIV VL and RLCV VL were independently associated with cancer. Local regressions showed that longitudinal VL patterns in cases and controls, from SIV infection to necropsy, differed for each gammaherpesvirus: while RFHV VL increased only slightly in all animals, RLCV and RRV VL increased significantly and continued to increase steeply in cases; in controls, VL flattened. In conclusion, the data suggest that gammaherpesviruses may play a significant role in tumorogenesis in macaques infected with immunodeficiency viruses.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aeromedical retrieval is an essential component of contemporary emergency care systems. However, in many locations, ground emergency medical services are dispatched to the scene of an incident first ...to assess the patient and then call for a helicopter if needed. The time to definitive care therefore includes the helicopter's flight to the scene, flight to the trauma center, and nonflying time. Mission ground time (MGT) includes the time required to get the helicopter airborne, as well as time spent at the scene, packaging and loading the casualty into the aircraft. Estimates of MGT typically vary from 10 to 30 min. The impact of MGT duration on population coverage—the number of residents that could be taken to a trauma center within a set time—is not known. The aim of this study was to compare population coverage for different durations of MGT in a single state.
Coverage was calculated using elliptical coverage areas (“isochrones”) based on the location of helicopter bases and Level I and Level II trauma centers. The calculations were performed using Microsoft Excel, assuming a cruising speed of 133 knots (246 km/h), and mapped using arcGIS. The access time threshold was set at 60 min, and we evaluated MGTs of 10, 15, 20, 25, and 30 min.
MGT has a marked impact on population coverage. The effect is, furthermore, not linear. When considering the state's three Level I trauma centers, decreasing MGT from 30 to 10 min increased population coverage from 61.2% to 84.2%. When also considering Level II centers, decreasing MGT from 30 min to 10 min increased coverage by 20%.
Elliptical isochrones, with allowance for MGT, provide realistic estimates of population coverage. MGT significantly impacts the proportion of the population that can be taken to a Level I and/or Level II Trauma Center within a set time. The impact is not linear, reflecting the uneven distribution of the population. Consideration should be given to minimizing MGT to preserve the benefits of aeromedical retrieval.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The International Mouse Phenotyping Consortium (IMPC) is providing the world’s first functional catalogue of a mammalian genome by characterising a knockout mouse strain for every gene. A robust and ...highly structured informatics platform has been developed to systematically collate, analyse and disseminate the data produced by the IMPC. As the first phase of the project, in which 5000 new knockout strains are being broadly phenotyped, nears completion, the informatics platform is extending and adapting to support the increasing volume and complexity of the data produced as well as addressing a large volume of users and emerging user groups. An intuitive interface helps researchers explore IMPC data by giving overviews and the ability to find and visualise data that support a phenotype assertion. Dedicated disease pages allow researchers to find new mouse models of human diseases, and novel viewers provide high-resolution images of embryonic and adult dysmorphologies. With each monthly release, the informatics platform will continue to evolve to support the increased data volume and to maintain its position as the primary route of access to IMPC data and as an invaluable resource for clinical and non-clinical researchers.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Click‐Chemie Ein vereinheitlichter Ansatz für die Click‐Chemie, genannt diversitätorientiertes Clicking, wird von J. E. Moses et al. im Forschungsartikel auf S. 12560 für die Synthese diverser ...Leitstrukturen eingeführt.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Diversity Oriented Clicking (DOC) is a unified click‐approach for the modular synthesis of lead‐like structures through application of the wide family of click transformations. DOC evolved from the ...concept of achieving “diversity with ease”, by combining classic C−C π‐bond click chemistry with recent developments in connective SuFEx‐technologies. We showcase 2‐Substituted‐Alkynyl‐1‐Sulfonyl Fluorides (SASFs) as a new class of connective hub in concert with a diverse selection of click‐cycloaddition processes. Through the selective DOC of SASFs with a range of dipoles and cyclic dienes, we report a diverse click‐library of 173 unique functional molecules in minimal synthetic steps. The SuFExable library comprises 10 discrete heterocyclic core structures derived from 1,3‐ and 1,5‐dipoles; while reaction with cyclic dienes yields several three‐dimensional bicyclic Diels–Alder adducts. Growing the library to 278 discrete compounds through late‐stage modification was made possible through SuFEx click derivatization of the pendant sulfonyl fluoride group in 96 well‐plates—demonstrating the versatility of the DOC approach for the rapid synthesis of diverse functional structures. Screening for function against MRSA (USA300) revealed several lead hits with improved activity over methicillin.
Diversity‐oriented clicking (DOC) is a unified click chemistry approach for the synthesis of diverse lead‐like structures. Herein DOC is showcased through the application of novel highly activated 2‐substituted‐alkynyl‐1‐sulfonyl fluoride (SASF) hubs in combination with a range of selective and robust click cycloaddition reactions, delivering an unprecedented SuFExable library of functional biologically active lead structures.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Click‐Chemie Ein vereinheitlichter Ansatz für die Click‐Chemie, genannt diversitätorientiertes Clicking, wird von J. E. Moses et al. im Forschungsartikel auf S. 12560 für die Synthese diverser ...Leitstrukturen eingeführt.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This paper describes the PROMOTE UV Record, which aims to provide a global long-term record of the surface UV radiation. The algorithm developed takes as input cloud information from the ...International Satellite Cloud Climatology Project (ISCCP) and a recently developed multisensor assimilated record of the total ozone column. Aerosols and surface albedo are based on climatologies. Here, first validation results of the PROMOTE UV Record are presented through comparison against ground-based measurements of daily erythemal UV doses at eight European stations. The validation shows that the method is working reasonably, although there is a clear tendency toward overestimation. Typically, the median bias as compared to measurements is 3%-10% and 56%-68% of the daily doses are within plusmn20% from the ground-based reference. The prototype version of the PROMOTE UV Record included in this paper covers the period from July 2002 to June 2005. The time series will later be extended to start in 1983.
The Human Phenotype Ontology in 2017 Köhler, Sebastian; Vasilevsky, Nicole A.; Engelstad, Mark ...
Nucleic acids research,
11/2016, Volume:
45, Issue:
D1
Journal Article
Peer reviewed
Open access
Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three ...components of the Human PhenotypeOntology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.
PDF
