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  • 1
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  • 2
    Keywords: TUMORS ; mechanisms ; ASSOCIATION ; SUSCEPTIBILITY ; ABERRATIONS ; MUTATIONS ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; ANEUPLOIDY ; GENOMIC IMBALANCES ; MAFFUCCI SYNDROME ; OLLIER DISEASE
    Abstract: In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of 〉 2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 x 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 x 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases
    Type of Publication: Journal article published
    PubMed ID: 22561519
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  • 3
    Keywords: EXPRESSION ; RISK ; COMPLEXES ; AMPLIFICATION ; OVARIAN-CANCER ; MUTATIONS ; VARIANT ; GENOME-WIDE ASSOCIATION ; GENETIC-VARIATION ; CONFERS SUSCEPTIBILITY
    Abstract: A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) 〉/= 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 x 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (Ptrend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. Cancer Res; 74(20); 5808-18. (c)2014 AACR.
    Type of Publication: Journal article published
    PubMed ID: 25320178
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  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  44. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 30. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 26. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR); 20160831-20160903; Frankfurt am Main; DOCSP.39 /20160829/
    Publication Date: 2016-08-29
    Keywords: Ankylosierende Spondylitis ; Erosion ; CT ; MRT ; ddc: 610
    Language: English
    Type: conferenceObject
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  • 5
    Keywords: GENETIC POLYMORPHISMS ; BREAST-CANCER ; COLORECTAL-CANCER ; CROHNS-DISEASE ; telomere length ; susceptibility loci ; RECOMBINATION HOTSPOTS ; CONFERS SUSCEPTIBILITY ; SEQUENCE VARIANT ; NAT2 SLOW ACETYLATION
    Abstract: Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P 〈 1 x 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 x 10(-9)) and rs907611 on 11p15.5 (P = 4.11 x 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 x 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 x 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.
    Type of Publication: Journal article published
    PubMed ID: 24163127
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  • 6
    ISSN: 1433-0490
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract. We present a randomized parallel algorithm for constructing the three-dimensional convex hull on a generic p-processor coarse-grained multicomputer with arbitrary interconnection network and n/p local memory per processor, where n/p ≥ p 2+ε (for some arbitrarily small ε 〉 0). For any given set of n points in 3-space, the algorithm computes the three-dimensional convex hull, with high probability, in $O((n\log{n})/p)$ local computation time and O(1) communication phases with at most O(n/p) data sent/received by each processor. That is, with high probability, the algorithm computes the three-dimensional convex hull of an arbitrary point set in time $O((n\log n)/{p} + \Gamma_{n,p})$ , where Γ n,p denotes the time complexity of one communication phase. The assumption n/p ≥ p 2+ε implies a coarse-grained, limited parallelism, model which is applicable to most commercially available multiprocessors. In the terminology of the BSP model, our algorithm requires, with high probability, O(1) supersteps, synchronization period $L = \Theta((n\log n)/{p})$ , computation cost $O((n\log n)/{p})$ , and communication cost O((n/p) g).
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2242
    Keywords: Key words Somatic hybridization ; Hexaploid ; RAPD ; Chromosome number variation ; Genetic improvement ; Aurantioideae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Chinese wampee [Clausena lansium (Lour.) Skeels], a sexually incompatible relative of citrus, is commercially cultivated in South China. In this study, embryogenic protoplasts of ‘Bonanza’ navel orange [Citrus sinensis (L.) Osbeck] were electrically fused with leaf protoplasts isolated from ‘Chicken Heart’ Chinese wampee. After 8 months of culture, fusion products regenerated into shoots. More than 70% of the shoots unexpectedly rooted well. Chromosome counting of several shoot- and root-tips revealed that their chromosome numbers were not 2n=4x=36 as expected, but 2n=6x=54, suggesting that chromosome doubling occurred rather than chromosome elimination in this intertribal fusion combination. RAPD analysis of embryoids and the leaves of unrooted and rooted shoots verified their hybridity. This is the first report of hexaploid somatic hybrid plant regeneration from fusion between diploids in Aurantioideae.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2242
    Keywords: Citrus ; Endosperm ; Triploid ; In vitro embryogenesis ; Plant breeding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Triploid hybrid Citrus plants were regenerated by somatic embryogenesis in vitro from endosperm derived calli. A sequence of media formulations was used to induce and support proliferation of primary callus from endosperm, to induce embryogenesis from primary callus, and to allow embryo development leading to viable plantlets. Calli were induced from cellular endosperm of Citrus sinensis (sweet orange), C. Xparadisi (grapefruit), and C. grandis (pummelo) excised 12–14 weeks post-anthesis. Induction of embryogenesis from sweet orange and pummelo primary calli required gibberellic acid and double mineral nutrient concentrations. Embryogenesis was not induced from grapefruit calli in these experiments. Only sweet orange embryos developed sufficiently to allow plant regeneration. Triploid axillary buds were minigrafted onto etiolated diploid rootstock seedlings in vitro in order to transfer triploid regenerants to soil and the external environment. Triploidy (2n = 3x = 27) was observed consistently in all phases of regeneration and in recovered plants. These results demonstrate that triploid hybrid plant recovery from Citrus endosperm can overcome barriers to sexual hybridization resulting from apomixis.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2285
    Keywords: Mineral nutrition ; Xylem sap ; Nitrogen isotope ; Juglans regia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Nitrogen (N) derived from both the soil during current-year uptake, and the withintree pool of storage N was distinguished in two groups of “Serr” walnut trees using labeled fertilizer (15N-depleted ammonium sulfate) applied in different years. Mass spectrometric analysis of N in xylem sap collected periodically in spring allowed quantification of the relative contributions of N from storage and current season uptake and the transition in N usage from previously assimilated (storage) N to the onset of current season uptake of soil N. N derived from storage accounted for 〉 50% of the xylem sap N during the staminate and pistillate bloom periods and throughout the period of spur leaf expansion.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Algorithmica 23 (1999), S. 14-30 
    ISSN: 1432-0541
    Keywords: Key words. Parallel computation, Competitive analysis, Communication delay, Scheduling, Compiler.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Mathematics
    Notes: Abstract. We apply the methodology of competitive analysis of algorithms to the implementation of programs on parallel machines. We consider the problem of finding the best on-line distributed scheduling strategy that executes in parallel an unknown directed acyclic graph (dag) which represents the data dependency relation graph of a parallel program and which is revealed as execution proceeds. We study the competitive ratio of some important classes of dags assuming a fixed communication delay ratio τ that captures the average interprocessor communication measured in instruction cycles. We provide competitive algorithms for divide-and-conquer dags, trees, and general dags, when the number of processors depends on the size of the input dag and when the number of processors is fixed. Our major result is a lower bound Ω (τ / log τ ) of the competitive ratio for trees; it shows that it is impossible to design compilers that produce almost optimal execution code for all parallel programs. This fundamental result holds for almost any reasonable distributed memory parallel computation model, including the LogP and BSP model.
    Type of Medium: Electronic Resource
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