22 research outputs found
Le West African Data and Metadata Repository : une archive de données à long terme pour les ensembles de données écologiques de l'Afrique de l'Ouest
Obwohl zunehmend Daten für ökologische Studien gebraucht werden, gehen noch immer viele Daten verloren oder sind mangels geeigneter Datenarchive nicht sichtbar genug. Mit dem West African Data and Metadata Repository stellen wir ein Langzeitdatenarchiv für eine datenarme Region vor, das eine detaillierte Dokumentation mit Metadaten nach dem EML-Standard erlaubt und Datenhaltern die Möglichkeit gibt, Datenzugangsebenen und Nutzungsbedingungen zu bestimmen. Dieser Artikel gibt einen Überblick zu Struktur, Funktionen und Inhalt. Das Repositorium ist online unter der URL http://westafricandata.senckenberg.de.Although there is an increasing need for data in ecological studies, many datasets are still lost or not sufficiently visible due to a lack of appropriate data archives. With the West African Data and Metadata Repository, we present a secure long-term archive for a data-poor region allowing detailed documentation by metadata following the EML standard and giving data holders the opportunity to define levels of data access and conditions of use. This article gives an overview of structure, functions and content. The repository is online at the URL http://westafricandata.senckenberg.de.Bien qu'il existe un besoin croissant de données dans les études écologiques, de nombreux ensembles de données sont encore perdues ou pas suffisamment visibles en raison d'un manque d'archives de données appropriées. Avec le West African Data and Metadata Repository, nous présentons une archive sécurisé à long terme pour une région pauvre en données permettant une documentation détaillée par des métadonnées suivant la norme EML et donnant aux propriétaires de données la possibilité de définir des niveaux de l'accès aux données et les conditions d'utilisation. Cet article donne un aperçu de la structure, des fonctions et du contenu. Le référentiel est en ligne à l'adresse URL http://westafricandata.senckenberg.de
De novo missense variants in FBXO11 alter its protein expression and subcellular localization.
Recently, we and others identified de novo FBXO11 variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant constructs in HEK293 and HeLa cells. We found that the majority of missense variants resulted in subcellular mislocalization and/or reduced FBXO11 protein expression levels. For instance, variants located in the nuclear localization signal and the N-terminal F-Box domain lead to altered subcellular localization with exclusion from the nucleus or the formation of cytoplasmic aggregates and to reduced protein levels in western blot. In contrast, variants localized in the C-terminal Zn-finger UBR domain lead to an accumulation in the cytoplasm without alteration of protein levels. Together with the mutational data our functional results suggest that most missense variants likely lead to a loss of the original FBXO11 function and thereby highlight haploinsufficiency as the most likely disease mechanism for FBXO11-associated NDDs
De novo missense variants in FBXO11 alter its protein expression and subcellular localization.
Recently, we and others identified de novo FBXO11 variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant constructs in HEK293 and HeLa cells. We found that the majority of missense variants resulted in subcellular mislocalization and/or reduced FBXO11 protein expression levels. For instance, variants located in the nuclear localization signal and the N-terminal F-Box domain lead to altered subcellular localization with exclusion from the nucleus or the formation of cytoplasmic aggregates and to reduced protein levels in western blot. In contrast, variants localized in the C-terminal Zn-finger UBR domain lead to an accumulation in the cytoplasm without alteration of protein levels. Together with the mutational data our functional results suggest that most missense variants likely lead to a loss of the original FBXO11 function and thereby highlight haploinsufficiency as the most likely disease mechanism for FBXO11-associated NDDs
Impact of land use and soil data specifications on COSMO-CLM simulations in the CORDEX-MED area
The impact of the ECOCLIMAP land use and the Harmonized World Soil Database (HWSD) data on simulations with the Consortium for Small-scale Modeling model in CLimate Mode (CCLM) regional climate model is investigated. ECOCLIMAP has information about vegetation characteristics as monthly data for 215 climatic units. With the HWSD implementation in CCLM, the spatial resolution of the soil data has been increased to 30 arc seconds and has an improved texture definition and handling in the soil model TERRA_ML. Simulations in the MED-CORDEX modeling domain over the period 1986–2000 reveal that differences of up to 1.8 K in the area monthly mean temperature as well as of up to 21 % in the area monthly mean precipitation can be attributed to the differences in the soil data time-invariant boundary input. Differences related to changes in land use are with 0.4 K and 5 % moderate. Differences resulting from the soil data and its processing in CCLM indicate that regional climate model simulations might benefit from further improvements in this area
Das West African Data and Metadata Repository : ein Langzeitdatenarchiv für ökologische Daten aus Westafrika
Although there is an increasing need for data in ecological studies, many datasets are still lost or not sufficiently visible due to a lack of appropriate data archives. With the West African Data and Metadata Repository, we present a secure long-term archive for a data-poor region allowing detailed documentation by metadata following the EML standard and giving data holders the opportunity to define levels of data access and conditions of use. This article gives an overview of structure, functions and content. The repository is online at the URL http://westafricandata.senckenberg.de.Bien qu'il existe un besoin croissant de données dans les études écologiques, de nombreux ensembles de données sont encore perdues ou pas suffisamment visibles en raison d'un manque d'archives de données appropriées. Avec le West African Data and Metadata Repository, nous présentons une archive sécurisé à long terme pour une région pauvre en données permettant une documentation détaillée par des métadonnées suivant la norme EML et donnant aux propriétaires de données la possibilité de définir des niveaux de l'accès aux données et les conditions d'utilisation. Cet article donne un aperçu de la structure, des fonctions et du contenu. Le référentiel est en ligne à l'adresse URL http://westafricandata.senckenberg.de.Obwohl zunehmend Daten für ökologische Studien gebraucht werden, gehen noch immer viele Daten verloren oder sind mangels geeigneter Datenarchive nicht sichtbar genug. Mit dem West African Data and Metadata Repository stellen wir ein Langzeitdatenarchiv für eine datenarme Region vor, das eine detaillierte Dokumentation mit Metadaten nach dem EML-Standard erlaubt und Datenhaltern die Möglichkeit gibt, Datenzugangsebenen und Nutzungsbedingungen zu bestimmen. Dieser Artikel gibt einen Überblick zu Struktur, Funktionen und Inhalt. Das Repositorium ist online unter der URL http://westafricandata.senckenberg.de
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ACRIN 6684: Multicenter, phase II assessment of tumor hypoxia in newly diagnosed glioblastoma using magnetic resonance spectroscopy
A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) "A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI (ACRIN 6684)", was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.5T or 3T. MRSI data were analyzed using LCModel to quantify metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate (Lac). Receiver operating characteristic curves for NAA/Cho, Cho/Cr, lactate/Cr, and lactate/NAA were constructed for overall survival at 1-year (OS-1) and 6-month progression free survival (PFS-6). The OS-1 for the 17 evaluable patients was 59% (10/17). Receiver operating characteristic analyses found the NAA/Cho in tumor (AUC = 0.83, 95% CI: 0.61 to 1.00) and in peritumoral regions (AUC = 0.95, 95% CI 0.85 to 1.00) were predictive for survival at 1 year. PFS-6 was 65% (11/17). Neither NAA/Cho nor Cho/Cr was effective in predicting 6-month progression free survival. Lac/Cr in tumor was a significant negative predictor of PFS-6, indicating that higher lactate/Cr levels are associated with poorer outcome. (AUC = 0.79, 95% CI: 0.54 to 1.00). In conclusion, despite the small sample size in the setting of a multi-center trial comprising different vendors, field strengths, and varying levels of expertise at data acquisition, MRS markers NAA/Cho, Lac/Cr and Lac/NAA predicted overall survival at 1 year and 6-month progression free survival. This study validates that MRSI may be useful in evaluating the prognosis in glioblastoma and should be considered for incorporating into multi-center clinical trials
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ACRIN 6684: Multicenter, phase II assessment of tumor hypoxia in newly diagnosed glioblastoma using magnetic resonance spectroscopy
A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) “A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI (ACRIN 6684)”, was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.5T or 3T. MRSI data were analyzed using LCModel to quantify metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate (Lac). Receiver operating characteristic curves for NAA/Cho, Cho/Cr, lactate/Cr, and lactate/NAA were constructed for overall survival at 1-year (OS-1) and 6-month progression free survival (PFS-6). The OS-1 for the 17 evaluable patients was 59% (10/17). Receiver operating characteristic analyses found the NAA/Cho in tumor (AUC = 0.83, 95% CI: 0.61 to 1.00) and in peritumoral regions (AUC = 0.95, 95% CI 0.85 to 1.00) were predictive for survival at 1 year. PFS-6 was 65% (11/17). Neither NAA/Cho nor Cho/Cr was effective in predicting 6-month progression free survival. Lac/Cr in tumor was a significant negative predictor of PFS-6, indicating that higher lactate/Cr levels are associated with poorer outcome. (AUC = 0.79, 95% CI: 0.54 to 1.00). In conclusion, despite the small sample size in the setting of a multi-center trial comprising different vendors, field strengths, and varying levels of expertise at data acquisition, MRS markers NAA/Cho, Lac/Cr and Lac/NAA predicted overall survival at 1 year and 6-month progression free survival. This study validates that MRSI may be useful in evaluating the prognosis in glioblastoma and should be considered for incorporating into multi-center clinical trials
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ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI.
PurposeStructural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma.Experimental designPrior to the start of chemoradiation, patients with glioblastoma underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (ktrans) as well as 18F-Fluoromisonidazole (18F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression-free and overall survival.ResultsFifty patients were enrolled of which 42 had evaluable imaging data. Higher pretreatment 18F-FMISO SUVpeak (P = 0.048), mean ktrans (P = 0.024), and median ktrans (P = 0.045) were significantly associated with shorter overall survival. Higher pretreatment median ktrans (P = 0.021), normalized RCBV (P = 0.0096), and nCBF (P = 0.038) were significantly associated with shorter progression-free survival. SUVpeak [AUC = 0.75; 95% confidence interval (CI), 0.59-0.91], nRCBV (AUC = 0.72; 95% CI, 0.56-0.89), and nCBF (AUC = 0.72; 95% CI, 0.56-0.89) were predictive of survival at 1 year.ConclusionsIncreased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed patients with gioblastoma, and these important physiologic markers can be measured safely and reliably using MRI and 18F-FMISO PET. Clin Cancer Res; 22(20); 5079-86. ©2016 AACR