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- Momozawa, Y, et al.
(författare)
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IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
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Tidskriftsartikel (refereegranskat)abstract
- GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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| 4. |
- Gottlob, H. D. B., et al.
(författare)
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Scaling potential and MOSFET integration of thermally stable Gd silicate dielectrics
- 2009
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Ingår i: Microelectronic Engineering. - : Elsevier BV. - 0167-9317 .- 1873-5568. ; 86:7-9, s. 1642-1645
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the potential of gadolinium silicate (GdSiO) as a thermally stable high-k gate dielectric in a gate first integration scheme. There silicon diffuses into gadolinium oxide (Gd2O3) from a silicon oxide (SiO2) interlayer specifically prepared for this purpose. We report on the scaling potential based on detailed material analysis. Gate leakage current densities and EOT values are compatible with an ITRS requirement for low stand by power (LSTP). The applicability of this GdSiO process is demonstrated by fully functional silicon on insulator (SOI) metal oxide semiconductor field effect transistors (MOSFETs). (C) 2009 Elsevier B.V. All rights reserved.
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| 5. |
- Liu, Jimmy Z, et al.
(författare)
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Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:6, s. 670-5
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Tidskriftsartikel (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.
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| 6. |
- Gottlob, H. D. B., et al.
(författare)
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Gd silicate : A high-k dielectric compatible with high temperature annealing
- 2009
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Ingår i: Journal of Vacuum Science & Technology B. - : American Vacuum Society. - 1071-1023 .- 1520-8567 .- 2166-2754 .- 2166-2746. ; 27:1, s. 249-252
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Tidskriftsartikel (refereegranskat)abstract
- The authors report on the investigation of amorphous Gd-based silicates as high-k dielectrics. Two different stacks of amorphous gadolinium oxide (Gd(2)O(3)) and silicon oxide (SiO(2)) on silicon substrates are compared after annealing at temperatures up to 1000 degrees C. Subsequently formed metal oxide semiconductor capacitors show a significant reduction in the capacitance equivalent thicknesses after annealing. Transmission electron microscopy, medium energy ion scattering, and x-ray diffraction analysis reveal distinct structural changes such as consumption of the SiO(2) layer and formation of amorphous Gd silicate. The controlled formation of Gd silicates in this work indicates a route toward high-k dielectrics compatible with conventional, gate first complementary metal-oxide semiconductor integration schemes.
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| 10. |
- Chiesa, Marco, 1987-, et al.
(författare)
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On the resiliency of randomized routing against multiple edge failures
- 2016
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Ingår i: 43rd International Colloquium on Automata, Languages, and Programming, ICALP 2016. - : Schloss Dagstuhl- Leibniz-Zentrum fur Informatik GmbH, Dagstuhl Publishing. - 9783959770132
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Konferensbidrag (refereegranskat)abstract
- We study the Static-Routing-Resiliency problem, motivated by routing on the Internet: Given a graph G = (V, E), a unique destination vertex d, and an integer constant c > 0, does there exist a static and destination-based routing scheme such that the correct delivery of packets from any source s to the destination d is guaranteed so long as (1) no more than c edges fail and (2) there exists a physical path from s to d? We embark upon a study of this problem by relating the edge-connectivity of a graph, i.e., the minimum number of edges whose deletion partitions G, to its resiliency. Following the success of randomized routing algorithms in dealing with a variety of problems (e.g., Valiant load balancing in the network design problem), we embark upon a study of randomized routing algorithms for the Static-Routing-Resiliency problem. For any k-connected graph, we show a surprisingly simple randomized algorithm that has expected number of hops O(|V|k) if at most k-1 edges fail, which reduces to O(|V|) if only a fraction t of the links fail (where t < 1 is a constant). Furthermore, our algorithm is deterministic if the routing does not encounter any failed link.
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