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- Carey, V, et al.
(author)
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Blockwise adaptivity for time dependent problems based on coarse scale adjoint solutions
- 2010
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In: SIAM Journal on Scientific Computing. - : Society for Industrial and Applied Mathematics. - 1064-8275 .- 1095-7197. ; 32:4, s. 2121-2145
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Journal article (peer-reviewed)abstract
- We describe and test an adaptive algorithm for evolution problems that employs a sequence of "blocks" consisting of fixed, though non-uniform, space meshes. This approach offers the advantages of adaptive mesh refinement but with reduced overhead costs associated with load balancing, re-meshing, matrix reassembly, and the solution of adjoint problems used to estimate discretization error and the effects of mesh changes. A major issue whith a blockadaptive approach is determining block discretizations from coarse scale solution information that achieve the desired accuracy. We describe several strategies to achieve this goal using adjoint-based a posteriori error estimates and we demonstrate the behavior of the proposed algorithms as well as several technical issues in a set of examples.
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- Haiman, Christopher A., et al.
(author)
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A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
- 2011
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:12, s. 61-1210
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Journal article (peer-reviewed)abstract
- Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 x 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 x 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 x 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.
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- Mielke, Michelle M, et al.
(author)
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Cerebrospinal fluid sphingolipids, β-amyloid, and tau in adults at risk for Alzheimer's disease.
- 2014
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In: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 35:11, s. 2486-94
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Journal article (peer-reviewed)abstract
- Cellular studies suggest sphingolipids may cause or accelerate amyloid-beta (Aβ) and tau pathology but invivo human studies are lacking. We determined cerebrospinal fluid levels of sphingolipids (ceramides and sphingomyelins), amyloid-beta (Aβ1-42, AβX-38, AβX-40, and AβX-42) and tau (T-tau and p-tau181) in 91 cognitively normal individuals, aged 36-69years, with a parental history of Alzheimer's disease. The 18-carbon acyl chain length ceramide species was associated with AβX-38 (r= 0.312, p= 0.003), AβX-40 (r= 0.327, p= 0.002), and T-tau (r= 0.313, p= 0.003) but not with AβX-42 (r= 0.171, p= 0.106) or p-tau (r= 0.086, p= 0.418). All sphingomyelin species correlated (most p < 0.001) with all Aβ species and T-tau; many also correlated with p-tau. Results remained in regression models after controlling for age and APOE genotype. These results suggest invivo relationships between cerebrospinal fluid ceramides and sphingomyelins and Aβ and tau levels in cognitively normal individuals at increased risk for Alzheimer's disease, indicating these sphingolipids may be associated with early pathogenesis.
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