TY - JOUR A1 - Banks, Jo Ann A1 - Nishiyama, Tomoaki A1 - Hasebe, Mitsuyasu A1 - Bowman, John L. A1 - Gribskov, Michael A1 - dePamphilis, Claude A1 - Albert, Victor A. A1 - Aono, Naoki A1 - Aoyama, Tsuyoshi A1 - Ambrose, Barbara A. A1 - Ashton, Neil W. A1 - Axtell, Michael J. A1 - Barker, Elizabeth A1 - Barker, Michael S. A1 - Bennetzen, Jeffrey L. A1 - Bonawitz, Nicholas D. A1 - Chapple, Clint A1 - Cheng, Chaoyang A1 - Correa, Luiz Gustavo Guedes A1 - Dacre, Michael A1 - DeBarry, Jeremy A1 - Dreyer, Ingo A1 - Elias, Marek A1 - Engstrom, Eric M. A1 - Estelle, Mark A1 - Feng, Liang A1 - Finet, Cedric A1 - Floyd, Sandra K. A1 - Frommer, Wolf B. A1 - Fujita, Tomomichi A1 - Gramzow, Lydia A1 - Gutensohn, Michael A1 - Harholt, Jesper A1 - Hattori, Mitsuru A1 - Heyl, Alexander A1 - Hirai, Tadayoshi A1 - Hiwatashi, Yuji A1 - Ishikawa, Masaki A1 - Iwata, Mineko A1 - Karol, Kenneth G. A1 - Koehler, Barbara A1 - Kolukisaoglu, Uener A1 - Kubo, Minoru A1 - Kurata, Tetsuya A1 - Lalonde, Sylvie A1 - Li, Kejie A1 - Li, Ying A1 - Litt, Amy A1 - Lyons, Eric A1 - Manning, Gerard A1 - Maruyama, Takeshi A1 - Michael, Todd P. A1 - Mikami, Koji A1 - Miyazaki, Saori A1 - Morinaga, Shin-ichi A1 - Murata, Takashi A1 - Müller-Röber, Bernd A1 - Nelson, David R. A1 - Obara, Mari A1 - Oguri, Yasuko A1 - Olmstead, Richard G. A1 - Onodera, Naoko A1 - Petersen, Bent Larsen A1 - Pils, Birgit A1 - Prigge, Michael A1 - Rensing, Stefan A. A1 - Mauricio Riano-Pachon, Diego A1 - Roberts, Alison W. A1 - Sato, Yoshikatsu A1 - Scheller, Henrik Vibe A1 - Schulz, Burkhard A1 - Schulz, Christian A1 - Shakirov, Eugene V. A1 - Shibagaki, Nakako A1 - Shinohara, Naoki A1 - Shippen, Dorothy E. A1 - Sorensen, Iben A1 - Sotooka, Ryo A1 - Sugimoto, Nagisa A1 - Sugita, Mamoru A1 - Sumikawa, Naomi A1 - Tanurdzic, Milos A1 - Theissen, Guenter A1 - Ulvskov, Peter A1 - Wakazuki, Sachiko A1 - Weng, Jing-Ke A1 - Willats, William W. G. T. A1 - Wipf, Daniel A1 - Wolf, Paul G. A1 - Yang, Lixing A1 - Zimmer, Andreas D. A1 - Zhu, Qihui A1 - Mitros, Therese A1 - Hellsten, Uffe A1 - Loque, Dominique A1 - Otillar, Robert A1 - Salamov, Asaf A1 - Schmutz, Jeremy A1 - Shapiro, Harris A1 - Lindquist, Erika A1 - Lucas, Susan A1 - Rokhsar, Daniel A1 - Grigoriev, Igor V. T1 - The selaginella genome identifies genetic changes associated with the evolution of vascular plants JF - Science N2 - Vascular plants appeared similar to 410 million years ago, then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes. We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported. By comparing gene content in evolutionarily diverse taxa, we found that the transition from a gametophyte- to a sporophyte-dominated life cycle required far fewer new genes than the transition from a nonseed vascular to a flowering plant, whereas secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in posttranscriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the trans-acting small interfering RNA pathway, and extensive RNA editing of organellar genes. Y1 - 2011 U6 - https://doi.org/10.1126/science.1203810 SN - 0036-8075 VL - 332 IS - 6032 SP - 960 EP - 963 PB - American Assoc. for the Advancement of Science CY - Washington ER - TY - JOUR A1 - Richter, Marina Juliane A1 - Schulz, Alexander A1 - Subkowski, Thomas A1 - Böker, Alexander T1 - Adsorption and rheological behavior of an amphiphilic protein at oil/water interfaces JF - Journal of colloid and interface science N2 - Hydrophobins are highly surface active proteins which self-assemble at hydrophilic-hydrophobic interfaces into amphipathic membranes. We investigate hydrophobin self-assembly at oil/water interfaces to deepen the understanding of protein behavior in order to improve our biomimetic synthesis. Therefore, we carried out pendant drop measurements of hydrophobin stabilized oil/water systems determining the time-dependent IFT and the dilatational rheology with additional adaptation to the Serrien protein model. We show that the class I hydrophobin H*Protein B adsorbs at an oil/water interface where it forms a densely-packed interfacial protein layer, which dissipates energy during droplet oscillation. Furthermore, the interfacial protein layer exhibits shear thinning behavior. (C) 2016 Elsevier Inc. All rights reserved. KW - Hydrophobin KW - Self-assembly KW - Pendant drop tensiometry KW - IFT KW - Rheology Y1 - 2016 U6 - https://doi.org/10.1016/j.jcis.2016.06.062 SN - 0021-9797 SN - 1095-7103 VL - 479 SP - 199 EP - 206 PB - Elsevier CY - San Diego ER - TY - GEN A1 - Gorski, Mathias A1 - Jung, Bettina A1 - Li, Yong A1 - Matias-Garcia, Pamela R. A1 - Wuttke, Matthias A1 - Coassin, Stefan A1 - Thio, Chris H. L. A1 - Kleber, Marcus E. A1 - Winkler, Thomas W. A1 - Wanner, Veronika A1 - Chai, Jin-Fang A1 - Chu, Audrey Y. A1 - Cocca, Massimiliano A1 - Feitosa, Mary F. A1 - Ghasemi, Sahar A1 - Hoppmann, Anselm A1 - Horn, Katrin A1 - Li, Man A1 - Nutile, Teresa A1 - Scholz, Markus A1 - Sieber, Karsten B. A1 - Teumer, Alexander A1 - Tin, Adrienne A1 - Wang, Judy A1 - Tayo, Bamidele O. A1 - Ahluwalia, Tarunveer S. A1 - Almgren, Peter A1 - Bakker, Stephan J. L. A1 - Banas, Bernhard A1 - Bansal, Nisha A1 - Biggs, Mary L. A1 - Boerwinkle, Eric A1 - Böttinger, Erwin A1 - Brenner, Hermann A1 - Carroll, Robert J. A1 - Chalmers, John A1 - Chee, Miao-Li A1 - Chee, Miao-Ling A1 - Cheng, Ching-Yu A1 - Coresh, Josef A1 - de Borst, Martin H. A1 - Degenhardt, Frauke A1 - Eckardt, Kai-Uwe A1 - Endlich, Karlhans A1 - Franke, Andre A1 - Freitag-Wolf, Sandra A1 - Gampawar, Piyush A1 - Gansevoort, Ron T. A1 - Ghanbari, Mohsen A1 - Gieger, Christian A1 - Hamet, Pavel A1 - Ho, Kevin A1 - Hofer, Edith A1 - Holleczek, Bernd A1 - Foo, Valencia Hui Xian A1 - Hutri-Kahonen, Nina A1 - Hwang, Shih-Jen A1 - Ikram, M. Arfan A1 - Josyula, Navya Shilpa A1 - Kahonen, Mika A1 - Khor, Chiea-Chuen A1 - Koenig, Wolfgang A1 - Kramer, Holly A1 - Kraemer, Bernhard K. A1 - Kuehnel, Brigitte A1 - Lange, Leslie A. A1 - Lehtimaki, Terho A1 - Lieb, Wolfgang A1 - Loos, Ruth J. F. A1 - Lukas, Mary Ann A1 - Lyytikainen, Leo-Pekka A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Melander, Olle A1 - Milaneschi, Yuri A1 - Mishra, Pashupati P. A1 - Mononen, Nina A1 - Mychaleckyj, Josyf C. A1 - Nadkarni, Girish N. A1 - Nauck, Matthias A1 - Nikus, Kjell A1 - Ning, Boting A1 - Nolte, Ilja M. A1 - O'Donoghue, Michelle L. A1 - Orho-Melander, Marju A1 - Pendergrass, Sarah A. A1 - Penninx, Brenda W. J. H. A1 - Preuss, Michael H. A1 - Psaty, Bruce M. A1 - Raffield, Laura M. A1 - Raitakari, Olli T. A1 - Rettig, Rainer A1 - Rheinberger, Myriam A1 - Rice, Kenneth M. A1 - Rosenkranz, Alexander R. A1 - Rossing, Peter A1 - Rotter, Jerome A1 - Sabanayagam, Charumathi A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Schoettker, Ben A1 - Schulz, Christina-Alexandra A1 - Sedaghat, Sanaz A1 - Shaffer, Christian M. A1 - Strauch, Konstantin A1 - Szymczak, Silke A1 - Taylor, Kent D. A1 - Tremblay, Johanne A1 - Chaker, Layal A1 - van der Harst, Pim A1 - van der Most, Peter J. A1 - Verweij, Niek A1 - Voelker, Uwe A1 - Waldenberger, Melanie A1 - Wallentin, Lars A1 - Waterworth, Dawn M. A1 - White, Harvey D. A1 - Wilson, James G. A1 - Wong, Tien-Yin A1 - Woodward, Mark A1 - Yang, Qiong A1 - Yasuda, Masayuki A1 - Yerges-Armstrong, Laura M. A1 - Zhang, Yan A1 - Snieder, Harold A1 - Wanner, Christoph A1 - Boger, Carsten A. A1 - Kottgen, Anna A1 - Kronenberg, Florian A1 - Pattaro, Cristian A1 - Heid, Iris M. T1 - Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline T2 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät - 19 KW - acute kidney injury KW - end-stage kidney disease KW - genome-wide association KW - study KW - rapid eGFRcrea decline Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-565379 IS - 19 ER - TY - JOUR A1 - Gorski, Mathias A1 - Jung, Bettina A1 - Li, Yong A1 - Matias-Garcia, Pamela R. A1 - Wuttke, Matthias A1 - Coassin, Stefan A1 - Thio, Chris H. L. A1 - Kleber, Marcus E. A1 - Winkler, Thomas W. A1 - Wanner, Veronika A1 - Chai, Jin-Fang A1 - Chu, Audrey Y. A1 - Cocca, Massimiliano A1 - Feitosa, Mary F. A1 - Ghasemi, Sahar A1 - Hoppmann, Anselm A1 - Horn, Katrin A1 - Li, Man A1 - Nutile, Teresa A1 - Scholz, Markus A1 - Sieber, Karsten B. A1 - Teumer, Alexander A1 - Tin, Adrienne A1 - Wang, Judy A1 - Tayo, Bamidele O. A1 - Ahluwalia, Tarunveer S. A1 - Almgren, Peter A1 - Bakker, Stephan J. L. A1 - Banas, Bernhard A1 - Bansal, Nisha A1 - Biggs, Mary L. A1 - Boerwinkle, Eric A1 - Böttinger, Erwin A1 - Brenner, Hermann A1 - Carroll, Robert J. A1 - Chalmers, John A1 - Chee, Miao-Li A1 - Chee, Miao-Ling A1 - Cheng, Ching-Yu A1 - Coresh, Josef A1 - de Borst, Martin H. A1 - Degenhardt, Frauke A1 - Eckardt, Kai-Uwe A1 - Endlich, Karlhans A1 - Franke, Andre A1 - Freitag-Wolf, Sandra A1 - Gampawar, Piyush A1 - Gansevoort, Ron T. A1 - Ghanbari, Mohsen A1 - Gieger, Christian A1 - Hamet, Pavel A1 - Ho, Kevin A1 - Hofer, Edith A1 - Holleczek, Bernd A1 - Foo, Valencia Hui Xian A1 - Hutri-Kahonen, Nina A1 - Hwang, Shih-Jen A1 - Ikram, M. Arfan A1 - Josyula, Navya Shilpa A1 - Kahonen, Mika A1 - Khor, Chiea-Chuen A1 - Koenig, Wolfgang A1 - Kramer, Holly A1 - Kraemer, Bernhard K. A1 - Kuehnel, Brigitte A1 - Lange, Leslie A. A1 - Lehtimaki, Terho A1 - Lieb, Wolfgang A1 - Loos, Ruth J. F. A1 - Lukas, Mary Ann A1 - Lyytikainen, Leo-Pekka A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Melander, Olle A1 - Milaneschi, Yuri A1 - Mishra, Pashupati P. A1 - Mononen, Nina A1 - Mychaleckyj, Josyf C. A1 - Nadkarni, Girish N. A1 - Nauck, Matthias A1 - Nikus, Kjell A1 - Ning, Boting A1 - Nolte, Ilja M. A1 - O'Donoghue, Michelle L. A1 - Orho-Melander, Marju A1 - Pendergrass, Sarah A. A1 - Penninx, Brenda W. J. H. A1 - Preuss, Michael H. A1 - Psaty, Bruce M. A1 - Raffield, Laura M. A1 - Raitakari, Olli T. A1 - Rettig, Rainer A1 - Rheinberger, Myriam A1 - Rice, Kenneth M. A1 - Rosenkranz, Alexander R. A1 - Rossing, Peter A1 - Rotter, Jerome A1 - Sabanayagam, Charumathi A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Schoettker, Ben A1 - Schulz, Christina-Alexandra A1 - Sedaghat, Sanaz A1 - Shaffer, Christian M. A1 - Strauch, Konstantin A1 - Szymczak, Silke A1 - Taylor, Kent D. A1 - Tremblay, Johanne A1 - Chaker, Layal A1 - van der Harst, Pim A1 - van der Most, Peter J. A1 - Verweij, Niek A1 - Voelker, Uwe A1 - Waldenberger, Melanie A1 - Wallentin, Lars A1 - Waterworth, Dawn M. A1 - White, Harvey D. A1 - Wilson, James G. A1 - Wong, Tien-Yin A1 - Woodward, Mark A1 - Yang, Qiong A1 - Yasuda, Masayuki A1 - Yerges-Armstrong, Laura M. A1 - Zhang, Yan A1 - Snieder, Harold A1 - Wanner, Christoph A1 - Boger, Carsten A. A1 - Kottgen, Anna A1 - Kronenberg, Florian A1 - Pattaro, Cristian A1 - Heid, Iris M. T1 - Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline JF - Kidney international : official journal of the International Society of Nephrology N2 - 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. KW - acute kidney injury KW - end-stage kidney disease KW - genome-wide association KW - study KW - rapid eGFRcrea decline Y1 - 2020 U6 - https://doi.org/10.1016/j.kint.2020.09.030 SN - 0085-2538 SN - 1523-1755 VL - 99 IS - 4 SP - 926 EP - 939 PB - Elsevier CY - New York ER - TY - JOUR A1 - Schulz, Irene A1 - Erle, Alexander A1 - Gräf, Ralph A1 - Krueger, Anne A1 - Lohmeier, Heiner A1 - Putzler, Sascha A1 - Samereier, Matthias A1 - Weidenthaler, Sebastian T1 - Identification and cell cycle-dependent localization of nine novel, genuine centrosomal components in Dictyostelium discoideum N2 - The centrosome is the main microtubule-organizing center and constitutes the largest protein complex in a eukaryotic cell. The Dictyostelium centrosome is an established model for acentriolar centrosomes and it consists of a layered core structure Surrounded by a so-called corona, which harbors microtubule nucleation complexes. We have identified 34 new centrosomal candidate proteins through mass spectrometrical analysis of the proteome of isolated Dictyostelium centrosomes. Here we present a characterization of 12 centrosomal candidate proteins all featuring coiled coil regions and low expression levels, which are the most common attributes of centrosomal proteins. We used GFP fusion proteins to localize the candidate proteins in whole cells and on microtubule-free, isolated centrosomes. Thus we were able to identify nine new genuine centrosomal proteins including a putative orthologue of Cep192, an interaction partner of polo-like kinase 4 in human centriole biogenesis. In this respect, centrosomal localization of the only polo-like kinase in Dictyostelium, Pik, is also shown in this work. Using confocal deconvolution microscopy, four components, CP39, CP55, CP75, and CP91 could be clearly assigned to the so far almost uncharacterized centrosomal core structure, while CP148 and Cep192 localized to a zone between that of corona marker and core proteins. Finally, CP103 and CP248 were constituents of the corona. In contrast, NE81 was localized at the nuclear envelope and three others, an orthologue of the spindle checkpoint component Mad1, the novel Cenp68, and the centrosomal CP248 were observed at the centromeres, which are clustered and linked to the centrosome throughout the entire cell cycle. Cell Motil. Cytoskeleton 66: 915-928, 2009. Y1 - 2009 UR - http://www3.interscience.wiley.com/cgi-bin/jhome/36113/ U6 - https://doi.org/10.1002/Cm.20384 SN - 0886-1544 ER - TY - JOUR A1 - Schulz, Irene A1 - Erle, Alexander A1 - Gräf, Ralph A1 - Krueger, Anne A1 - Putzler, Sascha A1 - Samereier, Matthias A1 - Weidenthaler, Sebastian T1 - Cell cycle-dependent localization of novel centrosomal and centromeric proteins in Dictyostelium Y1 - 2009 UR - http://www.sciencedirect.com/science/journal/01719335 U6 - https://doi.org/10.1016/S0171-9335(09)00023-5 SN - 0171-9335 ER - TY - JOUR A1 - Roggenbuck, Dirk A1 - Goihl, Alexander A1 - Hanack, Katja A1 - Holzloehner, Pamela A1 - Hentschel, Christian A1 - Veiczi, Miklos A1 - Schierack, Peter A1 - Reinhold, Dirk A1 - Schulz, Hans-Ulrich T1 - Serological diagnosis and prognosis of severe acute pancreatitis by analysis of serum glycoprotein 2 JF - Clinical chemistry and laboratory medicine : journal of the Forum of the European Societies of Clinical Chemistry - the European Branch of the International Federation of Clinical Chemistry and Laboratory Medicine N2 - To better understand emerging adults’ perceptions of family interactions and value transmission to the next generation, we examined Hmong American emerging adults’ reflections on their parents’ parenting. Participants discussed what parenting practices they would do differently and others they hoped to emulate with their future adolescent children. Thirty Hmong American emerging adults (18-25 years; M = 21.2 years; 50% female) participated in interviews that focused retrospectively on the parent–adolescent relationship. Results revealed that emerging adults wanted to parent differently in three ways: less pressure about education, fewer restrictions, and more open communication. Emerging adults imagined being a similar parent in four ways: promoting education, promoting life values, giving guidance, and offering love and support. The findings highlight parenting practices that Hmong American emerging adults plan on transmitting (and not transmitting) to their own children, offering a glimpse into the type of parents the emerging adults may become. KW - acute pancreatitis KW - chronic pancreatitis KW - GP2 isoform alpha KW - pancreatic neoplasms KW - severe acute pancreatitis KW - zymogen granule membrane glycoprotein GP2 Y1 - 2017 U6 - https://doi.org/10.1515/cclm-2016-0797 SN - 1434-6621 SN - 1437-4331 VL - 55 SP - 854 EP - 864 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Swidsinski, Alexander A1 - Loening-Baucke, Vera A1 - Schulz, Stefan A1 - Manowsky, Julia A1 - Verstraelen, Hans A1 - Swidsinski, Sonja T1 - Functional anatomy of the colonic bioreactor: Impact of antibiotics and Saccharomyces boulardii on bacterial composition in human fecal cylinders JF - Systematic and Applied Microbiology N2 - Sections of fecal cylinders were analyzed using fluorescence in situ hybridization targeting 180 bacterial groups. Samples were collected from three groups of women (N = 20 each) treated for bacterial vaginosis with ciprofloxacin + metronidazole. Group A only received the combined antibiotic regimen, whereas the A/Sb group received concomitant Saccharomyces boulardii CNCM I-745 treatment, and the A.Sb group received S. boulardii prophylaxis following the 14-day antibiotic course. The number of stool cylinders analyzed was 188 out of 228 in group A, 170 out of 228 in group A/Sb, and 172 out of 216 in group Ash. The colonic biomass was organized into a separate mucus layer with no bacteria, a 10-30 mu m broad unstirred transitional layer enriched with bacteria, and a patchy fermentative area that mixed digestive leftovers with bacteria. The antibiotics suppressed bacteria mainly in the fermentative area, whereas abundant bacterial clades retreated to the transitional mucus and survived. As a result, the total concentration of bacteria decreased only by one order. These effects were lasting, since the overall recovery of the microbial mass, bacterial diversity and concentrations were still below pre-antibiotic values 4 months after the end of antibiotic treatment. Sb-prophylaxis markedly reduced antibiotic effects and improved the recovery rates. Since the colon is a sophisticated bioreactor, the study indicated that the spatial anatomy of its biomass was crucial for its function. (C) 2015 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). KW - FISH KW - Colonic microbiota KW - Antibiotics KW - Bioreactor KW - Saccharomyces boulardii KW - Clostridium difficile Y1 - 2016 U6 - https://doi.org/10.1016/j.syapm.2015.11.002 SN - 0723-2020 VL - 39 SP - 67 EP - 75 PB - Nature Publ. Group CY - Jena ER - TY - JOUR A1 - Grinberg, Victoria A1 - Hell, Natalie A1 - El Mellah, Ileyk A1 - Neilsen, Joseph A1 - Sander, Andreas Alexander Christoph A1 - Leutenegger, Maurice A1 - Fürst, Felix A1 - Huenemoerder, David P. A1 - Kretschmar, Peter A1 - Kuehnel, Matthias A1 - Martinez-Nunez, Silvia A1 - Niu, Shu A1 - Pottschmidt, Katja A1 - Schulz, Norbert S. A1 - Wilms, Joern A1 - Nowak, Michael A. T1 - The clumpy absorber in the high-mass X-ray binary Vela X-1 JF - Astronomy and astrophysics : an international weekly journal N2 - Bright and eclipsing, the high-mass X-ray binary Vela X-1 offers a unique opportunity to study accretion onto a neutron star from clumpy winds of O/B stars and to disentangle the complex accretion geometry of these systems. In Chandra-HETGS spectroscopy at orbital phase similar to 0.25, when our line of sight towards the source does not pass through the large-scale accretion structure such as the accretion wake, we observe changes in overall spectral shape on timescales of a few kiloseconds. This spectral variability is, at least in part, caused by changes in overall absorption and we show that such strongly variable absorption cannot be caused by unperturbed clumpy winds of O/B stars. We detect line features from high and low ionization species of silicon, magnesium, and neon whose strengths and presence depend on the overall level of absorption. These features imply a co-existence of cool and hot gas phases in the system, which we interpret as a highly variable, structured accretion flow close to the compact object such as has been recently seen in simulations of wind accretion in high-mass X-ray binaries. KW - X-rays: individuals: Vela X-1 KW - X-rays: binaries KW - stars: winds, outflows KW - stars: massive Y1 - 2017 U6 - https://doi.org/10.1051/0004-6361/201731843 SN - 1432-0746 VL - 608 PB - EDP Sciences CY - Les Ulis ER - TY - THES A1 - Schulz, Alexander T1 - Untersuchung der Wechselwirkung synoptisch-skaliger mit orographisch bedingten Prozessen in der arktischen Grenzschicht über Spitzbergen N2 - In der vorliegenden Arbeit wird die planetare Grenzschicht in Ny-Ålesund, Spitzbergen, sowohl bezüglich kleinskaliger („mikrometeorologischer“) Effekte als auch in ihrer Kopplung mit der Synoptik untersucht. Dazu werden verschiedene Beobachtungsdaten aus der Säule und in Bodennähe zusammengezogen und bewertet. Die so gewonnenen Datensätze werden dann zur Validierung eines nicht-hydrostatischen, regionalen Klimamodells genutzt. Weiterhin werden orographisch bedingte Einflüsse, die Untergrundbeschaffenheit und die lokale Heterogenität der Unterlage untersucht. Hierzu werden meteorologische Größen, wie die Variabilität der Temperatur und insbesondere die jährliche Windverteilung in Bodennähe untersucht und es erfolgt ein Vergleich von in-situ gemessenen turbulenten Flüssen von den Eddy-Kovarianz-Messkomplexen bei Ny-Ålesund und im Bayelva-Tal unter demselben Aspekt. Es zeigt sich, dass der Eddy-Kovarianz-Messkomplex im Bayelva-Tal sehr stark durch eine orographisch bedingte Kanalisierung der Strömung beeinflusst ist und sich nicht für Vergleiche mit regionalen Klimamodellen mit horizontalen Auflösungen von <1km eignet. Die hohe Bodenfeuchte im Bayelva-Tal führt zudem zu einem deutlich kleineren Bowen-Verhältnis, als es für diese Region zu erwarten ist. Der Eddy-Kovarianz-Messkomplex bei Ny-Ålesund erweist sich hingegen als geeigneter für solche Modellvergleiche, aufgrund der typischen, küstennahen Windverteilung und des repräsentativen Footprints. Letzteres wird durch die Bestimmung der Footprint-Klimatologie des Jahres 2013 mit einem aktuellen Footprint-Modell erarbeitet. Weiterhin wird die Auswirkung von (Anti-) Zyklonen über den Archipel auf die zeitliche Variabilität der lokalen Grenzschichteigenschaften untersucht und bewertet. Dazu wird ein Zyklonen-Detektions-Algorithmus auf ERA-Interim-Reanalysedatensätze angewendet, wodurch die Häufigkeit von nahezu ideal konzentrischen Hoch- und die Tiefdruckgebieten für drei Jahre bestimmt wird. Aus dieser Verteilung werden insgesamt drei interessante Zeiträume zu verschiedenen Jahreszeiten ausgewählt und im Rahmen von Prozessstudien die lokalen bodennahen meteorologischen Messungen, der turbulente Austausch an der Oberfläche und die Grenzschichtdynamik in der Säule untersucht. Die zeitliche Variabilität der dynamischen Grenzschichtstabilität in der Säule wird anhand von zeitlich hoch aufgelösten vertikalen Profilen der Bulk-Richardson-Zahl aus Kompositprofilen aus Fernerkundungsinstrumenten (Radiometer, Wind-LIDAR) sowie Mastdaten (BSRN-Mast) untersucht und die Grenzschichthöhe ermittelt. Aus diesen Analysen ergibt sich eine deutliche Abhängigkeit der thermischen Stabilität beim Durchzug von Fronten, eine damit einhergehende erhebliche Abhängigkeit der Grenzschichtdynamik und der Grenzschichthöhe sowie des turbulenten Austauschs von der zeitlichen Variabilität der Windgeschwindigkeit in der Säule. Auf Grundlage der Standortanalysen und Prozessstudien erfolgt ein Vergleich der bodennahen Messungen und den Beobachtungen aus der Säule, sowohl von den genannten Fernerkundungsinstrumenten als auch von In-situ-Messungen (Radiosonden) für den Zeitraum einer Radiosondierungskampagne mit dem nicht-hydrostatischen, regionalen Klimamodel WRF (ARW). Auf Grundlage der Fragestellung, inwieweit aktuelle Schemata die Grenzschichtcharakteristika in orographisch stark gegliedertem Gelände in der Arktis reproduzieren können, werden zwei Grenzschichtparametrisierungsschemata mit verschiedenen Ordnungen der Schließung validiert. Hierzu wird die zeitliche Variabilität der Temperatur, der Feuchte und des Windfeldes in der Säule bis 2000m in den Simulationen mit den Beobachtungsdaten vergleichen. Es wird gezeigt, dass durch Modifikation der Initialwertfelder eine sehr gute Übereinstimmung zwischen den Simulationen und den Beobachtungen bereits bei einer horizontalen Auflösung von 1km erreicht werden kann und die Wahl des Grenzschichtschemas nur untergeordneten Einfluss hat. Hieraus werden Ansätze der Weiterentwicklung der Parametrisierungen, aber auch Empfehlungen bezüglich der Initialwertfelder, wie der Landmaske und der Orographie, vorgeschlagen. N2 - In this work, the planetary boundary layer in Ny-Ålesund, Svalbard is investigated both in terms of small scale (“micrometeorological”) effects and its connection to synoptic scale processes. Therefore several observational data from the lower troposphere and near the surface are added together and evaluated. These datasets are used to validate a non-hydrostatic, regional climate model. Furthermore orographically induced influences and the character of the surface and its local heterogeneity are investigated. To this, meteorological quantities like the temperature variability and the annual wind distribution near the surface are analysed and a comparison of in-situ measurements of the turbulent fluxes from the eddy covariance measuring complexes near Ny-Ålesund and in the Bayelva valley are conducted accordingly. It is shown that the eddy-covariance measuring complex in the Bayelva valley is influenced considerably by local channelling of the flow. Therefore this station is not suitable for comparisons with a regional climate model with horizontal resolutions ≥1km. In addition, higher soil moisture results in lower Bowen-ratio than expected for this site. It turned out that the eddy-covariance measuring complex near Ny-Ålesund is more appropriate for such model studies due to typical coastal wind distribution and a representative footprint. The latter is calculated by determining the footprint climatology of the year 2013 with a current footprint model. Furthermore the impact of (anti-) cyclones over the archipelago on the temporal variability of boundary layer characteristics is investigated and evaluated. For this purpose, a cyclone detection algorithm is applied to ERA-Interim reanalysis data which determines the frequency of nearly ideal concentric high and low pressure systems for three years. From this distribution, three interesting time periods are selected at different seasons and the local near surface meteorological measurements, the turbulent fluxes at the surface and the boundary layer dynamics in the column are examined in case studies. The temporal variability of the dynamic stability of the planetary boundary layer in the column is examined by temporally high resolved vertical profiles of the bulk Richardson number from composite profiles compiled from remote sensing data (radiometer, wind LIDAR) as well as data from the BSRN mast. From these analyses, a clear dependence of the thermal stability during the passage of fronts, a corresponding dependence of the boundary layer dynamics and the boundary layer height as well as the turbulent exchange from the temporal variability of the wind speed in the column results. On the basis of the site analyses and the case studies, a comparison of near surface measurements and observations from the column is made, both from the above-mentioned remote sensing instruments and in-situ measurements (radio soundings) for the period of an intense radio sounding campaign with the non-hydrostatic regional climate model WRF (ARW). On the basis of the question as to how far current schemes can reproduce the boundary layer characteristics in complex terrain in the Arctic, two boundary layer parameterization schemes with different orders of closure are validated. For this purpose, the temporal variability of the temperature, humidity and wind field in the column up to 2000m height in the simulations is compared with observational data. It is shown that by modifying fields of initial value, a very good agreement between the simulations and the observations can already be achieved with a horizontal resolution of 1km. The choice of the boundary layer scheme has only a minor influence. From this, approaches to the further development of the parameterizations as well as recommendations concerning the initial value fields, such as the land mask and the orography, are proposed. KW - atmosphärische Grenzschicht KW - atmospheric boundary layer KW - Mikrometeorologie KW - micrometeorology KW - regionale Klimamodellierung KW - regional climate modelling KW - Turbulenzmessung KW - turbulence measurement KW - arktische Atmosphäre KW - Arctic atmosphere Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-400058 ER - TY - GEN A1 - Beckmann, Nadine A1 - Becker, Katrin Anne A1 - Kadow, Stephanie A1 - Schumacher, Fabian A1 - Kramer, Melanie A1 - Kühn, Claudine A1 - Schulz-Schaeffer, Walter J. A1 - Edwards, Michael J. A1 - Kleuser, Burkhard A1 - Gulbins, Erich A1 - Carpinteiro, Alexander T1 - Acid sphingomyelinase deficiency ameliorates Farber disease T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1087 KW - Farber disease KW - lysosomal storage disorders KW - acid ceramidase KW - acid sphingomyelinase KW - amitriptyline Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-441282 SN - 1866-8372 IS - 1087 ER - TY - JOUR A1 - Beckmann, Nadine A1 - Kadow, Stephanie A1 - Schumacher, Fabian A1 - Goethert, Joachim R. A1 - Kesper, Stefanie A1 - Draeger, Annette A1 - Schulz-Schaeffer, Walter J. A1 - Wang, Jiang A1 - Becker, Jan U. A1 - Kramer, Melanie A1 - Kuehn, Claudine A1 - Kleuser, Burkhard A1 - Becker, Katrin Anne A1 - Gulbins, Erich A1 - Carpinteiro, Alexander T1 - Pathological manifestations of Farber disease in a new mouse model JF - Biological chemistry N2 - Farber disease (FD) is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments are clinically available and affected patients have a severely shortened lifespan. Due to the low incidence, the pathogenesis of FD is still poorly understood. Here, we report a novel acid ceramidase mutant mouse model that enables the study of pathogenic mechanisms of FD and ceramide accumulation. Asah1(tmEx1) mice were generated by deletion of the acid ceramidase signal peptide sequence. The effects on lysosomal targeting and activity of the enzyme were assessed. Ceramide and sphingomyelin levels were quantified by liquid chromatography tandem-mass spectrometry (LC-MS/MS) and disease manifestations in several organ systems were analyzed by histology and biochemistry. We show that deletion of the signal peptide sequence disrupts lysosomal targeting and enzyme activity, resulting in ceramide and sphingomyelin accumulation. The affected mice fail to thrive and die early. Histiocytic infiltrations were observed in many tissues, as well as lung inflammation, liver fibrosis, muscular disease manifestations and mild kidney injury. Our new mouse model mirrors human FD and thus offers further insights into the pathogenesis of this disease. In the future, it may also facilitate the development of urgently needed therapies. KW - acid ceramidase KW - ceramide KW - Farber disease KW - lysosomal storage disorders Y1 - 2018 U6 - https://doi.org/10.1515/hsz-2018-0170 SN - 1431-6730 SN - 1437-4315 VL - 399 IS - 10 SP - 1183 EP - 1202 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Beckmann, Nadine A1 - Becker, Katrin Anne A1 - Kadow, Stephanie A1 - Schumacher, Fabian A1 - Kramer, Melanie A1 - Kuehn, Claudine A1 - Schulz-Schaeffer, Walter J. A1 - Edwards, Michael J. A1 - Kleuser, Burkhard A1 - Gulbins, Erich A1 - Carpinteiro, Alexander T1 - Acid Sphingomyelinase Deficiency Ameliorates Farber Disease JF - International journal of molecular sciences N2 - Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients. KW - Farber disease KW - lysosomal storage disorders KW - acid ceramidase KW - acid sphingomyelinase KW - amitriptyline Y1 - 2019 U6 - https://doi.org/10.3390/ijms20246253 SN - 1422-0067 VL - 20 IS - 24 PB - MDPI CY - Basel ER - TY - BOOK A1 - Rana, Kaushik A1 - Mohapatra, Durga Prasad A1 - Sidorova, Julia A1 - Lundberg, Lars A1 - Sköld, Lars A1 - Lopes Grim, Luís Fernando A1 - Sampaio Gradvohl, André Leon A1 - Cremerius, Jonas A1 - Siegert, Simon A1 - Weltzien, Anton von A1 - Baldi, Annika A1 - Klessascheck, Finn A1 - Kalancha, Svitlana A1 - Lichtenstein, Tom A1 - Shaabani, Nuhad A1 - Meinel, Christoph A1 - Friedrich, Tobias A1 - Lenzner, Pascal A1 - Schumann, David A1 - Wiese, Ingmar A1 - Sarna, Nicole A1 - Wiese, Lena A1 - Tashkandi, Araek Sami A1 - van der Walt, Estée A1 - Eloff, Jan H. P. A1 - Schmidt, Christopher A1 - Hügle, Johannes A1 - Horschig, Siegfried A1 - Uflacker, Matthias A1 - Najafi, Pejman A1 - Sapegin, Andrey A1 - Cheng, Feng A1 - Stojanovic, Dragan A1 - Stojnev Ilić, Aleksandra A1 - Djordjevic, Igor A1 - Stojanovic, Natalija A1 - Predic, Bratislav A1 - González-Jiménez, Mario A1 - de Lara, Juan A1 - Mischkewitz, Sven A1 - Kainz, Bernhard A1 - van Hoorn, André A1 - Ferme, Vincenzo A1 - Schulz, Henning A1 - Knigge, Marlene A1 - Hecht, Sonja A1 - Prifti, Loina A1 - Krcmar, Helmut A1 - Fabian, Benjamin A1 - Ermakova, Tatiana A1 - Kelkel, Stefan A1 - Baumann, Annika A1 - Morgenstern, Laura A1 - Plauth, Max A1 - Eberhard, Felix A1 - Wolff, Felix A1 - Polze, Andreas A1 - Cech, Tim A1 - Danz, Noel A1 - Noack, Nele Sina A1 - Pirl, Lukas A1 - Beilharz, Jossekin Jakob A1 - De Oliveira, Roberto C. L. A1 - Soares, Fábio Mendes A1 - Juiz, Carlos A1 - Bermejo, Belen A1 - Mühle, Alexander A1 - Grüner, Andreas A1 - Saxena, Vageesh A1 - Gayvoronskaya, Tatiana A1 - Weyand, Christopher A1 - Krause, Mirko A1 - Frank, Markus A1 - Bischoff, Sebastian A1 - Behrens, Freya A1 - Rückin, Julius A1 - Ziegler, Adrian A1 - Vogel, Thomas A1 - Tran, Chinh A1 - Moser, Irene A1 - Grunske, Lars A1 - Szárnyas, Gábor A1 - Marton, József A1 - Maginecz, János A1 - Varró, Dániel A1 - Antal, János Benjamin ED - Meinel, Christoph ED - Polze, Andreas ED - Beins, Karsten ED - Strotmann, Rolf ED - Seibold, Ulrich ED - Rödszus, Kurt ED - Müller, Jürgen T1 - HPI Future SOC Lab – Proceedings 2018 N2 - 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 2018. Selected projects have presented their results on April 17th and November 14th 2017 at the Future SOC Lab Day events. N2 - Das Future SOC Lab am HPI ist eine Kooperation des Hasso-Plattner-Instituts mit verschiedenen Industriepartnern. Seine Aufgabe ist die Ermöglichung und Förderung des Austausches zwischen Forschungsgemeinschaft und Industrie. Am Lab wird interessierten Wissenschaftler:innen eine Infrastruktur von neuester Hard- und Software kostenfrei für Forschungszwecke zur Verfügung gestellt. Dazu zählen Systeme, die im normalen Hochschulbereich in der Regel nicht zu finanzieren wären, bspw. Server mit bis zu 64 Cores und 2 TB Hauptspeicher. Diese Angebote richten sich insbesondere an Wissenschaftler:innen in den Gebieten Informatik und Wirtschaftsinformatik. Einige der Schwerpunkte sind Cloud Computing, Parallelisierung und In-Memory Technologien. In diesem Technischen Bericht werden die Ergebnisse der Forschungsprojekte des Jahres 2018 vorgestellt. Ausgewählte Projekte stellten ihre Ergebnisse am 17. April und 14. November 2018 im Rahmen des Future SOC Lab Tags vor. T3 - Technische Berichte des Hasso-Plattner-Instituts für Digital Engineering an der Universität Potsdam - 151 KW - Future SOC Lab KW - research projects KW - multicore architectures KW - in-memory technology KW - cloud computing KW - machine learning KW - artifical intelligence KW - Future SOC Lab KW - Forschungsprojekte KW - Multicore Architekturen KW - In-Memory Technologie KW - Cloud Computing KW - maschinelles Lernen KW - künstliche Intelligenz Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-563712 SN - 978-3-86956-547-7 SN - 1613-5652 SN - 2191-1665 IS - 151 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Padash, Amin A1 - Aghion, Erez A1 - Schulz, Alexander A1 - Barkai, Eli A1 - Chechkin, Aleksei V. A1 - Metzler, Ralf A1 - Kantz, Holger T1 - Local equilibrium properties of ultraslow diffusion in the Sinai model JF - New journal of physics N2 - We perform numerical studies of a thermally driven, overdamped particle in a random quenched force field, known as the Sinai model. We compare the unbounded motion on an infinite 1-dimensional domain to the motion in bounded domains with reflecting boundaries and show that the unbounded motion is at every time close to the equilibrium state of a finite system of growing size. This is due to time scale separation: inside wells of the random potential, there is relatively fast equilibration, while the motion across major potential barriers is ultraslow. Quantities studied by us are the time dependent mean squared displacement, the time dependent mean energy of an ensemble of particles, and the time dependent entropy of the probability distribution. Using a very fast numerical algorithm, we can explore times up top 10(17) steps and thereby also study finite-time crossover phenomena. KW - Sinai diffusion KW - clustering KW - local equilibrium Y1 - 2022 U6 - https://doi.org/10.1088/1367-2630/ac7df8 SN - 1367-2630 VL - 24 IS - 7 PB - IOP Publishing CY - Bristol ER - TY - JOUR A1 - Wuttke, Matthias A1 - Li, Yong A1 - Li, Man A1 - Sieber, Karsten B. A1 - Feitosa, Mary F. A1 - Gorski, Mathias A1 - Tin, Adrienne A1 - Wang, Lihua A1 - Chu, Audrey Y. A1 - Hoppmann, Anselm A1 - Kirsten, Holger A1 - Giri, Ayush A1 - Chai, Jin-Fang A1 - Sveinbjornsson, Gardar A1 - Tayo, Bamidele O. A1 - Nutile, Teresa A1 - Fuchsberger, Christian A1 - Marten, Jonathan A1 - Cocca, Massimiliano A1 - Ghasemi, Sahar A1 - Xu, Yizhe A1 - Horn, Katrin A1 - Noce, Damia A1 - Van der Most, Peter J. A1 - Sedaghat, Sanaz A1 - Yu, Zhi A1 - Akiyama, Masato A1 - Afaq, Saima A1 - Ahluwalia, Tarunveer Singh A1 - Almgren, Peter A1 - Amin, Najaf A1 - Arnlov, Johan A1 - Bakker, Stephan J. L. A1 - Bansal, Nisha A1 - Baptista, Daniela A1 - Bergmann, Sven A1 - Biggs, Mary L. A1 - Biino, Ginevra A1 - Boehnke, Michael A1 - Boerwinkle, Eric A1 - Boissel, Mathilde A1 - Böttinger, Erwin A1 - Boutin, Thibaud S. A1 - Brenner, Hermann A1 - Brumat, Marco A1 - Burkhardt, Ralph A1 - Butterworth, Adam S. A1 - Campana, Eric A1 - Campbell, Archie A1 - Campbell, Harry A1 - Canouil, Mickael A1 - Carroll, Robert J. A1 - Catamo, Eulalia A1 - Chambers, John C. A1 - Chee, Miao-Ling A1 - Chee, Miao-Li A1 - Chen, Xu A1 - Cheng, Ching-Yu A1 - Cheng, Yurong A1 - Christensen, Kaare A1 - Cifkova, Renata A1 - Ciullo, Marina A1 - Concas, Maria Pina A1 - Cook, James P. A1 - Coresh, Josef A1 - Corre, Tanguy A1 - Sala, Cinzia Felicita A1 - Cusi, Daniele A1 - Danesh, John A1 - Daw, E. Warwick A1 - De Borst, Martin H. A1 - De Grandi, Alessandro A1 - De Mutsert, Renee A1 - De Vries, Aiko P. J. A1 - Degenhardt, Frauke A1 - Delgado, Graciela A1 - Demirkan, Ayse A1 - Di Angelantonio, Emanuele A1 - Dittrich, Katalin A1 - Divers, Jasmin A1 - Dorajoo, Rajkumar A1 - Eckardt, Kai-Uwe A1 - Ehret, Georg A1 - Elliott, Paul A1 - Endlich, Karlhans A1 - Evans, Michele K. A1 - Felix, Janine F. A1 - Foo, Valencia Hui Xian A1 - Franco, Oscar H. A1 - Franke, Andre A1 - Freedman, Barry I. A1 - Freitag-Wolf, Sandra A1 - Friedlander, Yechiel A1 - Froguel, Philippe A1 - Gansevoort, Ron T. A1 - Gao, He A1 - Gasparini, Paolo A1 - Gaziano, J. Michael A1 - Giedraitis, Vilmantas A1 - Gieger, Christian A1 - Girotto, Giorgia A1 - Giulianini, Franco A1 - Gogele, Martin A1 - Gordon, Scott D. A1 - Gudbjartsson, Daniel F. A1 - Gudnason, Vilmundur A1 - Haller, Toomas A1 - Hamet, Pavel A1 - Harris, Tamara B. A1 - Hartman, Catharina A. A1 - Hayward, Caroline A1 - Hellwege, Jacklyn N. A1 - Heng, Chew-Kiat A1 - Hicks, Andrew A. A1 - Hofer, Edith A1 - Huang, Wei A1 - Hutri-Kahonen, Nina A1 - Hwang, Shih-Jen A1 - Ikram, M. Arfan A1 - Indridason, Olafur S. A1 - Ingelsson, Erik A1 - Ising, Marcus A1 - Jaddoe, Vincent W. V. A1 - Jakobsdottir, Johanna A1 - Jonas, Jost B. A1 - Joshi, Peter K. A1 - Josyula, Navya Shilpa A1 - Jung, Bettina A1 - Kahonen, Mika A1 - Kamatani, Yoichiro A1 - Kammerer, Candace M. A1 - Kanai, Masahiro A1 - Kastarinen, Mika A1 - Kerr, Shona M. A1 - Khor, Chiea-Chuen A1 - Kiess, Wieland A1 - Kleber, Marcus E. A1 - Koenig, Wolfgang A1 - Kooner, Jaspal S. A1 - Korner, Antje A1 - Kovacs, Peter A1 - Kraja, Aldi T. A1 - Krajcoviechova, Alena A1 - Kramer, Holly A1 - Kramer, Bernhard K. A1 - Kronenberg, Florian A1 - Kubo, Michiaki A1 - Kuhnel, Brigitte A1 - Kuokkanen, Mikko A1 - Kuusisto, Johanna A1 - La Bianca, Martina A1 - Laakso, Markku A1 - Lange, Leslie A. A1 - Langefeld, Carl D. A1 - Lee, Jeannette Jen-Mai A1 - Lehne, Benjamin A1 - Lehtimaki, Terho A1 - Lieb, Wolfgang A1 - Lim, Su-Chi A1 - Lind, Lars A1 - Lindgren, Cecilia M. A1 - Liu, Jun A1 - Liu, Jianjun A1 - Loeffler, Markus A1 - Loos, Ruth J. F. A1 - Lucae, Susanne A1 - Lukas, Mary Ann A1 - Lyytikainen, Leo-Pekka A1 - Magi, Reedik A1 - Magnusson, Patrik K. E. A1 - Mahajan, Anubha A1 - Martin, Nicholas G. A1 - Martins, Jade A1 - Marz, Winfried A1 - Mascalzoni, Deborah A1 - Matsuda, Koichi A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Melander, Olle A1 - Metspalu, Andres A1 - Mikaelsdottir, Evgenia K. A1 - Milaneschi, Yuri A1 - Miliku, Kozeta A1 - Mishra, Pashupati P. A1 - Program, V. A. Million Veteran A1 - Mohlke, Karen L. A1 - Mononen, Nina A1 - Montgomery, Grant W. A1 - Mook-Kanamori, Dennis O. A1 - Mychaleckyj, Josyf C. A1 - Nadkarni, Girish N. A1 - Nalls, Mike A. A1 - Nauck, Matthias A1 - Nikus, Kjell A1 - Ning, Boting A1 - Nolte, Ilja M. A1 - Noordam, Raymond A1 - Olafsson, Isleifur A1 - Oldehinkel, Albertine J. A1 - Orho-Melander, Marju A1 - Ouwehand, Willem H. A1 - Padmanabhan, Sandosh A1 - Palmer, Nicholette D. A1 - Palsson, Runolfur A1 - Penninx, Brenda W. J. H. A1 - Perls, Thomas A1 - Perola, Markus A1 - Pirastu, Mario A1 - Pirastu, Nicola A1 - Pistis, Giorgio A1 - Podgornaia, Anna I. A1 - Polasek, Ozren A1 - Ponte, Belen A1 - Porteous, David J. A1 - Poulain, Tanja A1 - Pramstaller, Peter P. A1 - Preuss, Michael H. A1 - Prins, Bram P. A1 - Province, Michael A. A1 - Rabelink, Ton J. A1 - Raffield, Laura M. A1 - Raitakari, Olli T. A1 - Reilly, Dermot F. A1 - Rettig, Rainer A1 - Rheinberger, Myriam A1 - Rice, Kenneth M. A1 - Ridker, Paul M. A1 - Rivadeneira, Fernando A1 - Rizzi, Federica A1 - Roberts, David J. A1 - Robino, Antonietta A1 - Rossing, Peter A1 - Rudan, Igor A1 - Rueedi, Rico A1 - Ruggiero, Daniela A1 - Ryan, Kathleen A. A1 - Saba, Yasaman A1 - Sabanayagam, Charumathi A1 - Salomaa, Veikko A1 - Salvi, Erika A1 - Saum, Kai-Uwe A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Ben Schottker, A1 - Schulz, Christina-Alexandra A1 - Schupf, Nicole A1 - Shaffer, Christian M. A1 - Shi, Yuan A1 - Smith, Albert V. A1 - Smith, Blair H. A1 - Soranzo, Nicole A1 - Spracklen, Cassandra N. A1 - Strauch, Konstantin A1 - Stringham, Heather M. A1 - Stumvoll, Michael A1 - Svensson, Per O. A1 - Szymczak, Silke A1 - Tai, E-Shyong A1 - Tajuddin, Salman M. A1 - Tan, Nicholas Y. Q. A1 - Taylor, Kent D. A1 - Teren, Andrej A1 - Tham, Yih-Chung A1 - Thiery, Joachim A1 - Thio, Chris H. L. A1 - Thomsen, Hauke A1 - Thorleifsson, Gudmar A1 - Toniolo, Daniela A1 - Tonjes, Anke A1 - Tremblay, Johanne A1 - Tzoulaki, Ioanna A1 - Uitterlinden, Andre G. A1 - Vaccargiu, Simona A1 - Van Dam, Rob M. A1 - Van der Harst, Pim A1 - Van Duijn, Cornelia M. A1 - Edward, Digna R. Velez A1 - Verweij, Niek A1 - Vogelezang, Suzanne A1 - Volker, Uwe A1 - Vollenweider, Peter A1 - Waeber, Gerard A1 - Waldenberger, Melanie A1 - Wallentin, Lars A1 - Wang, Ya Xing A1 - Wang, Chaolong A1 - Waterworth, Dawn M. A1 - Bin Wei, Wen A1 - White, Harvey A1 - Whitfield, John B. A1 - Wild, Sarah H. A1 - Wilson, James F. A1 - Wojczynski, Mary K. A1 - Wong, Charlene A1 - Wong, Tien-Yin A1 - Xu, Liang A1 - Yang, Qiong A1 - Yasuda, Masayuki A1 - Yerges-Armstrong, Laura M. A1 - Zhang, Weihua A1 - Zonderman, Alan B. A1 - Rotter, Jerome I. A1 - Bochud, Murielle A1 - Psaty, Bruce M. A1 - Vitart, Veronique A1 - Wilson, James G. A1 - Dehghan, Abbas A1 - Parsa, Afshin A1 - Chasman, Daniel I. A1 - Ho, Kevin A1 - Morris, Andrew P. A1 - Devuyst, Olivier A1 - Akilesh, Shreeram A1 - Pendergrass, Sarah A. A1 - Sim, Xueling A1 - Boger, Carsten A. A1 - Okada, Yukinori A1 - Edwards, Todd L. A1 - Snieder, Harold A1 - Stefansson, Kari A1 - Hung, Adriana M. A1 - Heid, Iris M. A1 - Scholz, Markus A1 - Teumer, Alexander A1 - Kottgen, Anna A1 - Pattaro, Cristian T1 - A catalog of genetic loci associated with kidney function from analyses of a million individuals JF - Nature genetics N2 - 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. Y1 - 2019 U6 - https://doi.org/10.1038/s41588-019-0407-x SN - 1061-4036 SN - 1546-1718 VL - 51 IS - 6 SP - 957 EP - + PB - Nature Publ. Group CY - New York ER -