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- Ventura, M, et al.
(author)
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Recurrent sites for new centromere seeding
- 2004
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In: Genome research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 14:9, s. 1696-1703
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Journal article (peer-reviewed)abstract
- Using comparative FISH and genomics, we have studied and compared the evolution of chromosome 3 in primates and two human neocentromere cases on the long arm of this chromosome. Our results show that one of the human neocentromere cases maps to the same 3q26 chromosomal region where a new centromere emerged in a common ancestor of the Old World monkeys ∼25-40 million years ago. Similarly, the locus in which a new centromere was seeded in the great apes' ancestor was orthologous to the site in which a new centromere emerged in the New World monkeys' ancestor. These data suggest the recurrent use of longstanding latent centromeres and that there is an inherent potential of these regions to form centromeres. The second human neocentromere case (3q24) revealed unprecedented features. The neocentromere emergence was not accompanied by any chromosomal rearrangement that usually triggers these events. Instead, it involved the functional inactivation of the normal centromere, and was present in an otherwise phenotypically normal individual who transmitted this unusual chromosome to the next generation. We propose that the formation of neocentromeres in humans and the emergence of new centromeres during the course of evolution share a common mechanism.
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- Walsh, SH, et al.
(author)
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Mutated V-H genes and preferential V(H)3-21 use define new subsets of mantle cell lymphoma
- 2003
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 101:10, s. 4047-4054
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Journal article (peer-reviewed)abstract
- Mantle cell lymphoma (MCL) is believed to originate from a naive B cell. However, we recently demonstrated that a subset of MCL displayed mutated V-H genes. We also reported restricted use of certain V-H genes. To assess the prognostic impact of these new findings, we performed V-H gene analysis of 110 patients, revealing that 18 (16%) patients had mutated and 92 (84%) patients had unmutated V-H genes. Because the mutation rate was low in the mutated group (2.2%-6.7%), further investigation of the germline V-H gene in T cells from 5 patients with mutated V-H genes was carried out; results showed that the unrearranged V-H gene was identical to the published sequence. These data confirm that the base pair substitutions within the rearranged V-H genes represent hyper-mutations, and indicate germinal center exposure. However, V-H gene mutation status did not correlate with prognosis because there was no difference in clinical outcome between the unmutated and mutated groups. The most frequently used V-H genes were V(H)3-21 (21 patients) and V(H)4-34 (19 patients). A novel finding was that V(H)3-21(+) MCL almost exclusively ex-pressed X light chains and displayed highly restricted use of the V(lambda)3-19 gene. V(H)3-21(+) patients had longer median survival than the remaining patients (53 vs 34 months; P = .03), but they tended to be younger at diagnosis. The combined use Of V(H)3-21/V(lambda)3-19 suggests a possible role for antigen(s) in the pathogenesis of these tumors and indicates that V(H)3-21(+) patients constitute a new MCL entity. (C) 2003 by The American Society of Hematology.
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- Adlers, M, et al.
(author)
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Matrix stretching for sparse least squares problems
- 2000
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In: Numerical Linear Algebra with Applications. - 1070-5325 .- 1099-1506. ; 7:2, s. 51-65
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Journal article (peer-reviewed)abstract
- For linear least squares problems min(x) parallel to Ax - b parallel to(2) where A is sparse except for a few dense rows, a straightforward application of Cholesky or QR factorization will lead to catastrophic fill in the factor R. We consider handling such problems by a matrix stretching technique, where the dense rows are split into several more sparse rows. We develop both a recursive binary splitting algorithm and a more general splitting method. We show that for both schemes the stretched problem has the same set of solutions as the original least squares problem. Further. the condition number of the stretched problem differs from that of the original by only a modest factor, and hence the approach is numerically stable. Experimental results from applying the recursive binary scheme to a set of modified matrices from the Harwell-Boeing collection are given. We conclude that when A has a small number of dense rows relative to its dimension, there is a significant gain in sparsity of the factor R. A crude estimate of the optimal number of splits is obtained by analysing a simple model problem. Copyright (C) 2000 John Wiley & Sons, Ltd.
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