| 1. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 2. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 3. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 4. |
- Cho, Yoon Shin, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:1
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
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| 5. |
- Gasek, Nathan, et al.
(författare)
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Development of alginate and gelatin-based pleural and tracheal sealants
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061. ; 131, s. 222-235
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Tidskriftsartikel (refereegranskat)abstract
- Pleural and tracheal injuries remain significant problems, and an easy to use, effective pleural or tracheal sealant would be a significant advance. The major challenges are requirements for adherence, high strength and elasticity, dynamic durability, appropriate biodegradability, and lack of cell or systemic toxicity. We designed and evaluated two sealant materials comprised respectively of alginate methacrylate and of gelatin methacryloyl, each functionalized by conjugation with dopamine HCl. Both compounds are cross-linked into easily applied as pre-formed hydrogel patches or as in situ hydrogels formed at the wound site utilizing FDA-approved photo-initiators and oxidants. Material testing demonstrates appropriate adhesiveness, tensile strength, burst pressure, and elasticity with no significant cell toxicity in vitro assessments. Air-leak was absent after sealant application to experimentally-induced injuries in ex-vivo rat lung and tracheal models and in ex vivo pig lungs. Sustained repair of experimentally-induced pleural injury was observed for up to one month in vivo rat models and for up to 2 weeks in vivo rat tracheal injury models without obvious air leak or obvious toxicities. The alginate-based sealant worked best in a pre-formed hydrogel patch whereas the gelatin-based sealant worked best in an in situ formed hydrogel at the wound site thus providing two potential approaches. These studies provide a platform for further pre-clinical and potential clinical investigations. Statement of significance: Pneumothorax and pleural effusions resulting from trauma and a range of lung diseases and critical illnesses can result in lung collapse that can be immediately life-threatening or result in chronic leaking (bronchopleural fistula) that is currently difficult to manage. This leads to significantly increased morbidity, mortality, hospital stays, health care costs, and other complications. We have developed sealants originating from alginate and gelatin biomaterials, each functionalized by methacryloylation and by dopamine conjugation to have desired mechanical characteristics for use in pleural and tracheal injuries. The sealants are easily applied, non-cytotoxic, and perform well in vitro and in vivo model systems of lung and tracheal injuries. These initial proof of concept investigations provide a platform for further studies.
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| 6. |
- Hunter, Deidre A., et al.
(författare)
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A Study of Two Dwarf Irregular Galaxies with Asymmetrical Star Formation Distributions
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 855:1
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Tidskriftsartikel (refereegranskat)abstract
- Two dwarf irregular galaxies, DDO 187 and NGC 3738, exhibit a striking pattern of star formation: intense star formation is taking place in a large region occupying roughly half of the inner part of the optical galaxy. We use data on the H I distribution and kinematics and stellar images and colors to examine the properties of the environment in the high star formation rate (HSF) halves of the galaxies in comparison with the low star formation rate halves. We find that the pressure and gas density are higher on the HSF sides by 30%-70%. In addition we find in both galaxies that the H I velocity fields exhibit significant deviations from ordered rotation and there are large regions of high-velocity dispersion and multiple velocity components in the gas beyond the inner regions of the galaxies. The conditions in the HSF regions are likely the result of large-scale external processes affecting the internal environment of the galaxies and enabling the current star formation there.
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| 7. |
- Jeong, Yongkuk, et al.
(författare)
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An analysis of shipyard spatial arrangement planning problems and a spatial arrangement algorithm considering free space and unplaced block
- 2018
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Ingår i: The International Journal of Advanced Manufacturing Technology. - : Springer Nature. - 0268-3768 .- 1433-3015. ; 95:9-12, s. 4307-4325
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Tidskriftsartikel (refereegranskat)abstract
- The components of shipyard production systems can be classified into products, processes, facilities, space, humans, and schedules. The production capacity of a shipyard may vary depending on how they are operated. Particularly in the case of ships, it is important to efficiently utilize the limited space because they have large blocks, which are semi-finished products made during the shipbuilding process. To efficiently utilize the space, the locations of blocks must be determined taking various factors into consideration when arranging them in the workshop or stock area. This problem can be described as a spatial arrangement problem. However, as the items with fixed arrival dates and departure dates occupy the space for certain periods before being released from shipyards, this problem must be approached from the perspective of a spatial arrangement planning problem for certain periods and not as a simple spatial arrangement problem. In this study, various shipyard spatial arrangement planning problems are classified and defined based on arrangement areas, arrangement items, algorithms, and evaluation factors. In addition, taking the increasing sizes of shipyard blocks into consideration, evaluation factors and algorithms are proposed so that the shape of the free space and the characteristics of unplaced blocks can be considered in the spatial arrangement planning problems of large blocks. The performances of the proposed evaluation factors and algorithms were verified using block data generated by analyzing existing shipyard data product information. The proposed algorithm performed better than the existing algorithm for spatial arrangement planning problems of large blocks. However, the performance of the proposed algorithm was not significantly different from the existing algorithm when the size of the arrangement item was relatively small compared with the arrangement area.
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| 8. |
- Kim, Byung-Hyun, et al.
(författare)
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Indirect-to-Direct Band Gap Transition of Si Nanosheets : Effect of Biaxial Strain
- 2018
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 122:27, s. 15297-15303
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Tidskriftsartikel (refereegranskat)abstract
- The effect of biaxial strain on the band structure of two-dimensional silicon nanosheets (Si NSs) with (111), (110), and (001) exposed surfaces was investigated by means of density functional theory calculations. For all the considered Si NSs, an indirect-to-direct band gap transition occurs as the lateral dimensions of Si NSs increase; that is, increasing lateral biaxial strain from compressive to tensile always enhances the direct band gap characteristics. Further analysis revealed the mechanism of the transition which is caused by preferential shifts of the conduction band edge at a specific k-point because of their bond characteristics. Our results explain a photoluminescence result of the (111) Si NSs [U. Kim et al., ACS Nano 2011,.5, 2176-2181] in terms of the plausible tensile strain imposed in the unoxidized inner layer by surface oxidation.
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| 9. |
- Kim, Seonmyeong, et al.
(författare)
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Observing ice structure of micron-sized vapor-deposited ice with an x-ray free-electron laser
- 2023
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Ingår i: Structural Dynamics. - : AIP Publishing. - 2329-7778. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- The direct observation of the structure of micrometer-sized vapor-deposited ice is performed at Pohang Accelerator Laboratory x-ray free electron laser (PAL-XFEL). The formation of micrometer-sized ice crystals and their structure is important in various fields, including atmospheric science, cryobiology, and astrophysics, but understanding the structure of micrometer-sized ice crystals remains challenging due to the lack of direct observation. Using intense x-ray diffraction from PAL-XFEL, we could observe the structure of micrometer-sized vapor-deposited ice below 150 K with a thickness of 2-50 μm grown in an ultrahigh vacuum chamber. The structure of the ice grown comprises cubic and hexagonal sequences that are randomly arranged to produce a stacking-disordered ice. We observed that ice with a high cubicity of more than 80% was transformed to partially oriented hexagonal ice when the thickness of the ice deposition grew beyond 5 μm. This suggests that precise temperature control and clean deposition conditions allow μm-thick ice films with high cubicity to be grown on hydrophilic Si3N4 membranes. The low influence of impurities could enable in situ diffraction experiments of ice nucleation and growth from interfacial layers to bulk ice.
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| 10. |
- Lee, Heon-Woo, et al.
(författare)
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Endothelium-derived lactate is required for pericyte function and blood-brain barrier maintenance
- 2022
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Ingår i: EMBO Journal. - : EMBO Press. - 0261-4189 .- 1460-2075. ; 41:9
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial cells differ from other cell types responsible for the formation of the vascular wall in their unusual reliance on glycolysis for most energy needs, which results in extensive production of lactate. We find that endothelium-derived lactate is taken up by pericytes, and contributes substantially to pericyte metabolism including energy generation and amino acid biosynthesis. Endothelial-pericyte proximity is required to facilitate the transport of endothelium-derived lactate into pericytes. Inhibition of lactate production in the endothelium by deletion of the glucose transporter-1 (GLUT1) in mice results in loss of pericyte coverage in the retina and brain vasculatures, leading to the blood-brain barrier breakdown and increased permeability. These abnormalities can be largely restored by oral lactate administration. Our studies demonstrate an unexpected link between endothelial and pericyte metabolisms and the role of endothelial lactate production in the maintenance of the blood-brain barrier integrity. In addition, our observations indicate that lactate supplementation could be a useful therapeutic approach for GLUT1 deficiency metabolic syndrome patients.
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