This thesis aims to address offshore wind energy (OWE)-related environmental impacts. It includes the future material demand for the manufacturing of OWE turbines and foundations, the cradle-to-the... Show moreThis thesis aims to address offshore wind energy (OWE)-related environmental impacts. It includes the future material demand for the manufacturing of OWE turbines and foundations, the cradle-to-the-grave environmental impacts of global OWE development, the impacts on marine biodiversity, and other impacts on the environment. Show less
The prokaryotic chemotaxis system is arguably the best-understood signaling pathway in biology. In all previously described species, chemoreceptors organize into a hexagonal (P6 symmetry) extended... Show moreThe prokaryotic chemotaxis system is arguably the best-understood signaling pathway in biology. In all previously described species, chemoreceptors organize into a hexagonal (P6 symmetry) extended array. Here, we report an alternative symmetry (P2) of the chemotaxis apparatus that emerges from a strict linear organization of the histidine kinase CheA in Treponema denticola cells, which possesses arrays with the highest native curvature investigated thus far. Using cryo-ET, we reveal that Td chemoreceptor arrays assume an unusual arrangement of the supra-molecular protein assembly that has likely evolved to accommodate the high membrane curvature. The arrays have several atypical features, such as an extended dimerization domain of CheA and a variant CheW-CheR-like fusion protein that is critical for maintaining an ordered chemosensory apparatus. Furthermore, the previously characterized Td oxygen sensor ODP influences CheA ordering. These results suggest a greater diversity of the chemotaxis signaling system than previously thought. Show less
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results... Show moreLeukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease. Show less
This dissertation offers a narrative perspective of the power dynamics between the Buddha and his disciples. It selects multiple narratives revolving around figures from the early monastic... Show moreThis dissertation offers a narrative perspective of the power dynamics between the Buddha and his disciples. It selects multiple narratives revolving around figures from the early monastic community as represented by Śāriputra, Devadatta, Ānanda, and Kāśyapa, who attempt to compete with, challenge, or succeed the Buddha. My treatment of the Devadatta narratives in their historical development and ideological complexities reveals that the Devadatta narrative itself is a body of multilayered, ever-changing and self-reflective rhetoric, whose pivotal function is to cope with the potential problems substantialized by Devadatta’s challenges to the Buddha. All of the vibrant stories I analyze here, which are wide-ranging in terms of geography and chronology, are open windows into the Buddhist self-understanding of fundamental theological questions concerning the nature and significance of the buddha and the identity of being a Buddhist, as well as practical issues such as how to maintain their authority and accommodate their updated needs in an age without a buddha. Seeking its methodological basis in philology, history, and literary theory, this dissertation sheds light on the dynamic interplay between narratives and ideologies and enhances our understanding of the significance of narrative in reflecting and stimulating new ideologies and constructing histories of early Buddhism. Show less
Teumer, A.; Qi, Q.; Nethander, M.; Aschard, H.; Bandinelli, S.; Beekman, M.; ... ; Body Composition Genetics Consorti 2017
Ulcerative colitis is a chronic, relapsing inflammatory condition of the gastrointestinal tract with a complex genetic and environmental etiology. In an effort to identify genetic variation... Show moreUlcerative colitis is a chronic, relapsing inflammatory condition of the gastrointestinal tract with a complex genetic and environmental etiology. In an effort to identify genetic variation underlying ulcerative colitis risk, we present two distinct genome-wide association studies of ulcerative colitis and their joint analysis with a previously published scan(1), comprising, in aggregate, 2,693 individuals with ulcerative colitis and 6,791 control subjects. Fifty-nine SNPs from 14 independent loci attained an association significance of P < 10(-5). Seven of these loci exceeded genome-wide significance (P < 5 x 10(-8)). After testing an independent cohort of 2,009 cases of ulcerative colitis and 1,580 controls, we identified 13 loci that were significantly associated with ulcerative colitis (P < 5 x 10(-8)), including the immunoglobulin receptor gene FCGR2A, 5p15, 2p16 and ORMDL3 (orosomucoid1-like 3). We confirmed association with 14 previously identified ulcerative colitis susceptibility loci, and an analysis of acknowledged Crohn's disease loci showed that roughly half of the known Crohn's disease associations are shared with ulcerative colitis. These data implicate approximately 30 loci in ulcerative colitis, thereby providing insight into disease pathogenesis. Show less
