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Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
The “HPI Future SOC Lab” is a cooperation of the Hasso Plattner Institute (HPI) and industry partners. Its mission is to enable and promote exchange and interaction between the research community and the industry partners.
The HPI Future SOC Lab provides researchers with free of charge access to a complete infrastructure of state of the art hard and software. This infrastructure includes components, which might be too expensive for an ordinary research environment, such as servers with up to 64 cores and 2 TB main memory. The offerings address researchers particularly from but not limited to the areas of computer science and business information systems. Main areas of research include cloud computing, parallelization, and In-Memory technologies.
This technical report presents results of research projects executed in 2017. Selected projects have presented their results on April 25th and November 15th 2017 at the Future SOC Lab Day events.
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.
Synthesis of 3D flower-like zinc-nitrilotriacetic acid (ZnNTA) mesocrystals and their conformal transformation to hierarchically porous N-doped carbon superstructures is reported. During the solvothermal reaction, 2D nanosheet primary building blocks undergo oriented attachment and mesoscale assembly forming stacked layers. The secondary nucleation and growth preferentially occurs at the edges and defects of the layers, leading to formation of 3D flower-like mesocrystals comprised of interconnected 2D micropetals. By simply varying the pyrolysis temperature (550-1000 degrees C) and the removal method of in the situ-generated Zn species, nonporous parent mesocrystals are transformed to hierarchically porous carbon flowers with controllable surface area (970-1605 m(2) g(-1)), nitrogen content (3.4-14.1 at%), pore volume (0.95-2.19 cm(3) g(-1)), as well as pore diameter and structures. The carbon flowers prepared at 550 degrees C show high CO2/N-2 selectivity due to the high nitrogen content and the large fraction of (ultra)micropores, which can greatly increase the CO2 affinity. The results show that the physicochemical properties of carbons are highly dependent on the thermal transformation and associated pore formation process, rather than directly inherited from parent precursors. The present strategy demonstrates metal-organic mesocrystals as a facile and versatile means toward 3D hierarchical carbon superstructures that are attractive for a number of potential applications.
Reversible assembly of the V0V1 holoenzyme from V-0 and V-1 subcomplexes is a widely used mechanism for regulation of vacuolar-type H+-ATPases (V-ATPases) in animal cells. in the blowfly (Calliphora vicina) salivary gland, V- ATPase is located in the apical membrane of the secretory cells and energizes the secretion of a KCl-rich saliva in response to the hormone serotonin. We have examined whether the CAMP pathway, known to be activated by serotonin, controls V-ATPase assembly and activity. Fluorescence measurements of pH changes at the luminal surface of isolated glands demonstrate that CAMP, Sp-adenosine-3',5'-cyclic monophosphorothioate, or forskolin, similar to serotonin, cause V-ATPase-dependent luminal acidification. In addition, V-ATPase-dependent ATP hydrolysis increases upon treatment with these agents. Immunofluorescence microscopy and pelleting assays have demonstrated further that V, components become translocated from the cytoplasm to the apical membrane and V-ATPase holoenzymes are assembled at the apical membrane during conditions that increase intracellular cAMP. Because these actions occur without a change in cytosolic Ca2+, our findings suggest that the cAMP pathway mediates the reversible assembly and activation of V-ATPase molecules at the apical membrane upon hormonal stimulus
Representatives of the genus Stentor (Stentoridae, Heterotrichea) are striking ciliates in environmental water samples because of their size (up to 4 mm) and their trumpet-like shape. Important for species identification are the following main characteristics: (1) the presence or absence of endosymbiotic algae (zoochlorellae); (2) the colour of the pigmented cortical granules, and (3) the shape of the macronucleus. The complete small subunit rDNA (SSU rDNA) of 19 further representatives of the genus Stentor was sequenced to examine the phylogenetic relationships within this genus and to determine the taxonomic value of these main characteristics. The detailed phylogenetic analyses yielded a separation of all species possessing a single compact macronucleus from those species with an "elongated" macronucleus (moniliform or vermiform). The data also indicate that the uptake of algae as well as the loss of pigmentation happened independently in different lineages. Furthermore, a high level of intraspecific variation within several species was found. Thus, S. muelleri and S. (sp.) cf. katashimai appear to represent distinct species and S. multiformis is composed of a species complex.
Die Validität des autobiographischen Gedächtnisses wird kontrovers diskutiert, bislang fehlen prospektive Längsschnittstudien weitgehend. Die vorliegende Studie überprüft die Validität des autobiographischen Gedächtnisses anhand der Daten einer prospektiven epidemiologischen Längsschnittstudie, die in vier Untersuchungswellen 399 achtjährige Kinder bis zum Alter von 25 Jahren begleitete. Im Alter von 25 Jahren wurden die Erinnerungsleistungen der Probanden an Kernfakten, Erziehungsstil der Eltern, eigene psychische Probleme sowie Lebensereignisse aus Kindheit und Jugend mit Hilfe eines voll strukturierten Fragebogens erhoben. Mit Ausnahme der Kernfakten waren die Erinnerungsleistungen durchweg schlecht, intelligente Probanden zeigten insgesamt bessere Erinnerungsleistungen, junge Erwachsene mit psychischen Störungen berichteten vermehrt auch früher nicht vorhandene Symptome. Die retrospektive Erfassung früherer Lebensereignisse, der Beziehung zu den Eltern und psychischer Auffälligkeiten im Rahmen von Risikostudien und klinischen Studien ist sehr bedenklich. Schlüsselwörter: Autobiographisches Gedächtnis, Entwicklungspsychopathologie, Epidemiologie, Langzeitstudie, Methodik
Fragestellung: Prospektive Bedeutung von Risikofaktoren des Kindes- und Jugendalters für externalisierende und internalisierende Störungen. Methode: Prospektive Längsschnittstudie vom Grundschul- zum frühen Erwachsenenalter. 321 Personen nahmen an allen Untersuchungen im Alter von 8, 13, 18 und 25 Jahren teil. Ergebnisse: Es zeigte sich, daß psychische Störungen in hohem Maße geschlechtsabhängig sind. Besonders groß waren die Unterschiede im frühen Erwachsenenalter, wobei internalisierende Störungen bei Frauen und externalisierende Störungen bei Männern deutlich überwogen. Externalisierende Störungen des Erwachsenenalters ließen sich besser vorhersagen als internalisierende Störungen. Dies ließ sich vor allem durch die größere prädiktive Bedeutung früher Risikofaktoren bis zum Alter von 8 Jahren erklären. Für die Vorhersage internalisierender Störungen war hingegen der Einfluß der Risikofaktoren des späten Jugendalters und des Übergangs zum Erwachsenenalter größer. 10% der untersuchten Stichprobe wies persistente Störungen auf und stellt damit eine Hochrisikogruppe dar. Dieser Verlaufstyp zeichnet sich durch stabil hohe Risikokonstellationen zu allen Untersuchungszeitpunkten aus. Schlüsselwörter: Risikofaktoren, Prävalenz, Geschlechtsunterschiede, Verlaufstypen, externalisierende Störungen, internalisierende Störungen, psychische Störungen, Kindes- und Jugendalter, Erwachsenenalter Childhood and adolescent predictors of mental disorders from childhood to early adulthood. Abstract. Objectives: Prospective impact of child and adolescent risk factors on externalizing and internalizing disorders. Methods: Prospective longitudinal study from childhood to early adulthood. 321 persons participated at age 8, 13, 18 and 25 years. Results: Sex differences in the prevalence rates of mental disorders were found. The highest differences were found in early adulthood. Females showed higher rates of internalizing disorders, whereas males showed higher rates of externalizing disorders. Externalizing disorders in adulthood could be predicted better than internalizing disorders. This result could be explained by the greater predictive power of childhood risk factors for externalizing disorders. Risk factors of adolescence and the transmission period to adulthood played a more prominent role in the prediction of internalizing disorders. 10% of the studied sample showed persistent disorders and was identified as a high-risk sample. This developmental pattern of mental disorders shows stable risk constellations from childhood to adulthood. Key words: risk factors, prevalence, sex differences, developmental patterns, externalizing disorders, internalizing disorders, mental disorders, childhood and adolescence, adulthood
The Apache Modeling Project
(2004)
This document presents an introduction to the Apache HTTP Server, covering both an overview and implementation details. It presents results of the Apache Modelling Project done by research assistants and students of the Hasso–Plattner–Institute in 2001, 2002 and 2003. The Apache HTTP Server was used to introduce students to the application of the modeling technique FMC, a method that supports transporting knowledge about complex systems in the domain of information processing (software and hardware as well). After an introduction to HTTP servers in general, we will focus on protocols and web technology. Then we will discuss Apache, its operational environment and its extension capabilities— the module API. Finally we will guide the reader through parts of the Apache source code and explain the most important pieces.
The volume provides a field-analytical methodology for researching knowledge based sociopolitical processes of transnationalization. Drawing on the seminal work by Pierre Bourdieu, we apply concepts of practice, habitus, and field to phenomena such as cross-national social trajectories, international procedures of evaluation, standardization and certification or supranational political structures. These transnational phenomena form part of general political struggles that legitimate social relationships in and beyond the nation state. Part 1 on "Methodological Foundations" discusses the consequences of Bourdieu's epistemology and methodology for theorizing and investigating transnational phenomena. The contributions show the import of field-theoretical concepts for post-national insights. Part 2 on "Investigating Political Fields" presents exemplary case studies in diverse research areas such as colonial imperialism, international academic rankings, European policy fields, and local school policy. While focusing on their research objects, the contributions also give an insight into the mechanisms involved in processes of transnationalization. The volume is an invitation for sociologists, political scientists and scholars in adjacent research areas to engage with reflexive and relational research practice and to further develop field-theoretical thought.
Self-assembly of block copolymers is a significant area of polymer science. The self-assembly of completely water-soluble block copolymers is of particular interest, albeit a challenging task. In the present work the self-assembly of a linear-brush architecture block copolymer, namely poly(N-vinylpyrrolidone)-b-poly(oligoethylene glycol methacrylate) (PVP-b-POEGMA), in water is studied. Moreover, the assembled structures are crosslinked via alpha-CD host/guest complexation in a supramolecular way. The crosslinking shifts the equilibrium toward aggregate formation without switching off the dynamic equilibrium of double hydrophilic block copolymer (DHBC). As a consequence, the self-assembly efficiency is improved without extinguishing the unique DHBC self-assembly behavior. In addition, decrosslinking could be induced without a change in concentration by adding a competing complexation agent for alpha-CD. The self-assembly behavior was followed by DLS measurement, while the presence of the particles could be observed via cryo-TEM before and after crosslinking.
Das Heft dokumentiert die siebte Konferenz des Forschungskreises Vereinte Nationen, die am 23. und 24. Juni 2006 an der Universität Potsdam stattfand. Unter dem Titel „Ein Jahr nach dem UN-Weltgipfel 2005 – Eine Bilanz der Reformbemühungen “ widmete sich die Konferenz wichtigen strukturellen Fragen und nahm einzelne Tätigkeitsfelder der Weltorganisation in den Blick. Die aus unterschiedlichen Disziplinen und aus Wissenschaft und Praxis kommenden Referentinnen und Referenten ziehen in den Referaten eine kritische Bilanz und untersuchen, was den Erklärungen des feierlichen Weltgipfels vom September 2005 an konkreten Reformschritten gefolgt ist. In für die „Potsdamer UNO-Konferenzen“ typischer Weise wird allen Interessierten die Möglichkeit gegeben, wichtige Aspekte der aktuellen Diskussion kennenzulernen, welche vor allem die Reform der UN-Hauptorgane, Reformen im Entwicklungssystem der Vereinten Nationen und im Bereich der Überwachung von Menschenrechtsverträgen betreffen sowie Fragen der Friedenssicherung und die Beteiligung von Zivilgesellschaft und Parlamentariern. Außerdem würdigt die Broschüre schweizerische Reforminitiativen in den UN und dokumentiert die aktuelle Diskussion über die deutschsprachige UN-Forschung.