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A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
We prove statistical rates of convergence for kernel-based least squares regression from i.i.d. data using a conjugate gradient algorithm, where regularization against overfitting is obtained by early stopping. This method is related to Kernel Partial Least Squares, a regression method that combines supervised dimensionality reduction with least squares projection. Following the setting introduced in earlier related literature, we study so-called "fast convergence rates" depending on the regularity of the target regression function (measured by a source condition in terms of the kernel integral operator) and on the effective dimensionality of the data mapped into the kernel space. We obtain upper bounds, essentially matching known minimax lower bounds, for the L^2 (prediction) norm as well as for the stronger Hilbert norm, if the true
regression function belongs to the reproducing kernel Hilbert space. If the latter assumption is not fulfilled, we obtain similar convergence rates for appropriate norms, provided additional unlabeled data are available.
Towards an understanding of climate proxy formation in the Chew Bahir basin, southern Ethiopian Rift
(2018)
Deciphering paleoclimate from lake sediments is a challenge due to the complex relationship between climate parameters and sediment composition. Here we show the links between potassium (K) concentrations in the sediments of the Chew Bahir basin in the Southern Ethiopian Rift and fluctuations in the catchment precipitation/evaporation balance. Our micro-X-ray fluorescence and X-ray diffraction results suggest that the most likely process linking climate with potassium concentrations is the authigenic illitization of smectites during episodes of higher alkalinity and salinity in the closed -basin lake, due to a drier climate. Whole-rock and clay size fraction analyses suggest that illitization of the Chew Bahir clay minerals with increasing evaporation is enhanced by octahedral Al-to-Mg substitution in the clay minerals, with the resulting layer charge increase facilitating potassium-fixation. Linking mineralogy with geochemistry shows the links between hydroclimatic control, process and formation of the Chew Bahir K patterns, in the context of well-known and widely documented eastern African climate fluctuations over the last 45,000 years. These results indicate characteristic mineral alteration patterns associated with orbitally controlled wet-dry cycles such as the African Humid Period (similar to 15-5 ka) or high-latitude controlled climate events such as the Younger Dryas (similar to 12.8-11.6 ka) chronozone. Determining the impact of authigenic mineral alteration on the Chew Bahir records enables the interpretation of the previously established pXRF-derived aridity proxy K and provides a better paleohydrological understanding of complex climate proxy formation.
Eine verbesserte Zusammenarbeit und Abstimmung von Fachwissenschaft, Fachdidaktik, Bildungswissenschaften und schulpraktischen Lernorten ist einer der Förderbereiche der „Qualitätsoffensive Lehrerbildung“. Zahlreiche der geförderten Projekte haben für dieses Handlungsfeld im Bereich Vernetzung von Fachwissenschaft, Fachdidaktik und Bildungswissenschaften hochschulspezifische Maßnahmen konzipiert und umgesetzt.
Der vorliegende Tagungsband beinhaltet Beiträge von 15 entsprechenden Projekten, von denen sieben anlässlich von zwei standortübergreifenden Projekt-Tagungen in Hannover und Potsdam vorgestellt und in Workshops diskutiert wurden. Insgesamt geben die Beiträge einen theoretisch fundierten und gleichzeitig praxisorientierten Überblick über aktuelle Ansätze und Konzepte zur besseren Vernetzung fachwissenschaftlicher, fachdidaktischer und bildungswissenschaftlicher Studienanteile im Lehramtsstudium. Dargestellt werden Projektarbeiten der Hochschulen, die auf verschiedenen Ebenen wirksam werden (curricular-inhaltliche Ebene, kollegiale Ebene, hochschul-strukturelle Ebene). Die Maßnahmen sind so beschrieben, dass sie als Grundlage für einen Transfer auf andere Fächer bzw. andere Standorte genutzt werden können.
Die Beiträge richten sich an alle Lehrenden im Bereich der Lehramtsbildung sowie sonstige Akteure im Bereich der Lehr- und Qualitätsentwicklung an den Universitäten. Sie alle können den beschriebenen Konzepten und Umsetzungsformaten transferierbare Ideen und Impulse entnehmen.