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  • 1
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Communications in Numerical Methods in Engineering 10 (1994), S. 961-970 
    ISSN: 1069-8299
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: New developments of describing the theoretical basis towards an effective virtual-pulse (VIP) time integral methodology are proposed for general non-linear transient heat transfer problems. Primarily to validate the proposed methodology of computation, simple numerical test cases are provided and comparisons are also drawn with the implicit second-order-accurate Crank-Nicolson method. For the models tested, the proposed method has comparable or improved accuracy and stability characteristics. The VIP methodology introduced here for tackling non-linear thermal problems offers attractive features and is a viable alternative to traditional time-stepping practices. Efforts are underway to demonstrate the practical applicability to multi-dimensional thermal analysis.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 39 (1996), S. 1955-1977 
    ISSN: 0029-5981
    Keywords: structural dynamics ; finite elements ; algorithms ; Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: An overview of new and recent advances towards a VIrtual-Pulse (VIP) time-integral methodology for general linear/non-linear dynamic systems is presented. Attention is focused on providing a brief overview and an indepth evaluation of the developments, methodology, computational issues and implementation aspects for practical problems. Different from the way we have been looking at the developments encompassing existing direct time-integration type methods and mode superposition techniques, the proposed methodology capitalizes on the computational attributes of both and thereby offers new perspectives and several attractive favourable features in terms of stability and accuracy, storage, and computational costs for a wide variety of inertial dynamic problems. Recently, the authors have shown the theoretical developments via the VIP methodology for transient structural problems and for transient thermal problems. The purpose of the present paper is to summarize the theoretical developments, improve upon the computational/implementation aspects for general linear/non-linear dynamic structural problems, and demonstrate the pros and cons via numerous illustrative test cases. The theoretical analysis and results of several test cases show that the VIP methodology has improved accuracy/stability characteristics and computational advantages in comparison to the commonly advocated explicit and implicit methods such as the Newmark family. Overall, an analysis of the theoretical developments, algorithmic study, and the implementation and evaluation of the formulations strongly suggest the proposition that the VIP methodology is a viable alternative for general structural dynamic applications encountered in practical engineering problems.
    Additional Material: 15 Ill.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Chichester [u.a.] : Wiley-Blackwell
    International Journal for Numerical Methods in Engineering 39 (1996), S. 721-739 
    ISSN: 0029-5981
    Keywords: contact ; impact ; structural dynamics ; explicit methods ; Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: New explicit dynamic computational developments in conjunction with finite element formulations for impact problems are described in this paper. The proposed methodology is based on employing a variational inequality for dynamic problems involving Coulomb friction with the so-called forward incremental displacement-central difference method specially formulated in this paper for this class of problems. To enforce the constraints on the contact boundary, a linear complementary equation is established by means of a minimization problem subjected to constraints, which is equivalent to discretization of the variational inequality of the dynamic problem. In conjunction with these developments, a new conjugate gradient based explicit solution strategy is described for effectively solving the linear complementary equations. With the motivation for providing effective computational procedures suitable for vectorization and parallel computations, the proposed developments not only provide a fundamentally sound and robust theoretical basis but also serve to be ideally suited for impact problems involving frictional contact on high speed computing environments.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Publication Date: 2014-06-14
    Description: Purpose: A let-7 microRNA-complementary site (LCS6) polymorphism in the 3' untranslated region of the KRAS gene has been shown to disrupt let-7 binding and upregulate KRAS expression. We evaluated the LCS6 genotype and its association with KRAS mutation status, clinicopathologic features, and disease-free survival (DFS) in patients with stage III colon cancer who enrolled in a phase III clinical trial (NCCTG N0147). Experimental Design: The LCS6 genotype was assayed by real-time PCR in DNA extracted from whole blood ( n = 2,834) and compared with paired tumor tissue ( n = 977). 2 and two-sample t tests were used to compare baseline factors and KRAS mutation status between patients defined by LCS6 variant status. Log-rank tests and multivariate Cox models assessed associations between LCS6 status and DFS, respectively. Results: We identified 432 (15.2%) blood samples and 143 (14.6%) tumor samples heterozygous or homozygous for the LCS6 G-allele, and 2,402 of 2,834 (84.8%) blood samples and 834 of 977 (85.4%) tumor samples homozygous for the LCS6 T-allele. Genotype results were highly concordant (99.8%) in cases with paired blood and tumor tissue ( n = 977). G-allele carriers were significantly more frequent in Caucasians versus other races ( 2 test, P 〈 0.0001). The LCS6 genotype was not associated with KRAS mutation status, clinicopathologic features (all P 〉 0.2), or DFS (log-rank P = 0.49; HR, 0.929; 95% confidence interval, 0.76–1.14), even after combining LCS6 genotype with KRAS mutation status. Conclusions: In the largest association study investigating the LCS6 polymorphism in colon cancers, the germline LCS6 genotype was not associated with KRAS mutation status or with clinical outcome in patients with stage III tumors. Clin Cancer Res; 20(12); 3319–27. ©2014 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 5
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    The American Association for Cancer Research (AACR)
    Publication Date: 2014-03-04
    Description: Abundant epidemiologic evidence indicates that regular and long-term use of aspirin is associated with a significant reduction in the incidence of colorectal cancer. The long duration of aspirin needed to prevent colorectal cancer is believed to be due to inhibition of precursor lesions known as adenomas, the recurrence of which is inhibited by aspirin in randomized trials. Aspirin intake has also been associated with a statistically significant improvement in patient survival after curative resection of colorectal cancer in large observational studies. In these cohorts, the survival benefit of aspirin was shown to depend upon the level of COX-2 expression in the primary colorectal cancer. More recent analysis of patient tumors from these observational cohorts suggests that the benefit of aspirin may be limited to specific molecular subtypes. Aspirin intake following colorectal cancer resection was associated with a significant improvement of survival in patients whose tumors carried mutant, but not wild-type, copies of the phosphoinositide 3-kinase ( PI3KCA ) gene, especially tumors that overexpressed COX-2. A mechanistic explanation is suggested by the finding that inhibition of COX-mediated prostaglandin E2 synthesis by aspirin attenuates PI3K signaling activity that is known to regulate cancer cell proliferation and survival. Aspirin has also been shown to reduce the incidence of colorectal cancers bearing wild-type, but not mutant alleles of the BRAF V600E oncogene. Although provocative, the potential utility of these molecular markers for predicting aspirin efficacy awaits prospective evaluation in clinical trials. If validated, these findings may support a personalized approach to using aspirin for the therapy of colorectal cancer. Clin Cancer Res; 20(5); 1087–94. ©2013 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 6
    Publication Date: 2011-11-29
    Description: Author(s): X. W. Sha, D. A. Papaconstantopoulos, M. J. Mehl, and N. Bernstein [Phys. Rev. B 84, 184109] Published Mon Nov 28, 2011
    Keywords: Structure, structural phase transitions, mechanical properties, defects
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
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  • 7
    Publication Date: 2013-04-02
    Description: Charcot–Marie–Tooth disease type 1C (CMT1C) is a dominantly inherited motor and sensory neuropathy. Despite human genetic evidence linking missense mutations in SIMPLE to CMT1C, the in vivo role of CMT1C-linked SIMPLE mutations remains undetermined. To investigate the molecular mechanism underlying CMT1C pathogenesis, we generated transgenic mice expressing either wild-type or CMT1C-linked W116G human SIMPLE. Mice expressing mutant, but not wild type, SIMPLE develop a late-onset motor and sensory neuropathy that recapitulates key clinical features of CMT1C disease. SIMPLE mutant mice exhibit motor and sensory behavioral impairments accompanied by decreased motor and sensory nerve conduction velocity and reduced compound muscle action potential amplitude. This neuropathy phenotype is associated with focally infolded myelin loops that protrude into the axons at paranodal regions and near Schmidt–Lanterman incisures of peripheral nerves. We find that myelin infolding is often linked to constricted axons with signs of impaired axonal transport and to paranodal defects and abnormal organization of the node of Ranvier. Our findings support that SIMPLE mutation disrupts myelin homeostasis and causes peripheral neuropathy via a combination of toxic gain-of-function and dominant-negative mechanisms. The results from this study suggest that myelin infolding and paranodal damage may represent pathogenic precursors preceding demyelination and axonal degeneration in CMT1C patients.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 8
    Publication Date: 2016-12-10
    Description: Bone marrow fibrosis grade is an independent risk factor for overall survival in patients with primary myelofibrosis Blood Cancer Journal 6, e505 (December 2016). doi:10.1038/bcj.2016.116 Authors: B Li, P Zhang, G Feng, Z Xu, T Qin, Y Zhang, Z Sha, D Dong, H Zhang, L Fang, L Pan, N Hu, S Qu, W Cai, G Huang & Z Xiao
    Electronic ISSN: 2044-5385
    Topics: Medicine
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