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  • 1
    Abstract: TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%+/-8.7%, respectively (p〈0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%+/-2% vs. 57.4%+/-1.8% (p〈0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p〈0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%+/-1.5% in lithium treated cells vs. 56.6+/-3% (p〈0.01)) accompanied by increased number of gammaH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%+/-8% for lithium treated cells vs. 27%+/-3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
    Type of Publication: Journal article published
    PubMed ID: 25539912
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  • 2
    ISSN: 1588-2780
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Samarium-153-EDTMP (ethylene diamine tetramethylene phosphonate), for its promising biological properties, has been proved as a palliating therapeutic agent for boné cancer in human beings. In this article, we present the results on synthesis and structure analysis of Samarium-153-EDTMP. In a basic medium,153Sm-EDTMP can be readily prepared with a complexing yield not less than 98%, and it is confirmed that the ratio of the ligand to Sm is 1∶1, and the charge of153Sm-EDTMP is negative two.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1619-6937
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Summary The interaction of plane time-harmonic SH-waves with micro-cracks in transversely isotropic materials is investigated. Elastic wave scattering by a single micro-crack is first analyzed. The scattered displacement is expressed as a Fourier integral containing the crack opening displacement. By using this representation formula and by invoking the traction-free boundary condition on the faces of the crack, a boundary integral equation for the unknown crack opening displacement is obtained. Expanding the crack opening displacement into a series of Chebyshev polynomials and adopting a Galerkin method, the boundary integral equation is converted into an infinite system of inear algebraic equations for the expansion coefficients which is solved numerically. Numerical results are presented for the elastodynamic stress intensity factors, the scattered far-field and the scattering cross section of a single crack. Then, propagation of plane time-harmonic SH-waves in a transversely isotropicmaterial permeated by a random and dilute distribution of micro-cracks is investigated. The effects of the micro-crack density on the attenuation coefficient and the phase velocity are analyzed by appealing to a simple energy consideration and by using Kramers-Kronig relations.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Acta mechanica 83 (1990), S. 187-193 
    ISSN: 1619-6937
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Summary Some new conservation laws or path-independent integrals for transient elastodynamics are presented. Their applications in transient elastodynamic crack analysis are discussed.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-4862
    Keywords: Ultrasound ; reflection ; transmission ; layer of cracks
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology , Mathematics
    Notes: Abstract Reflection and transmission of ultrasonic waves by a layer-like region of distributed microcracks in a bulk material has been investigated. It has been assumed that for sufficiently low frequencies and far away from the damaged layer, the reflected and transmitted waves are plane waves. By applying the Betti reciprocal theorem to a cell containingN cracks, and by choosing one elastodynamic state as the actual wave state and the other as a suitably chosen auxiliary wave state, the reflection and transmission coefficients have been expressed in terms of integrals over theN cracks. Simple expressions have been obtained for the case that all cracks are identical and parallel to each other. For the case that the cracks do not interact with each other, numerical results for the reflection and transmission coefficients are presented for a distribution of penny-shaped cracks. The variation of these coefficients with frequency, relative layer thickness and angle of incidence has been displayed in graphs.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A three-dimensional (3-D) time-domain boundary integral equation method (BIEM) is presented for transient elastodynamic crack analysis. A non-hypersingular traction BIE formulation is used with the crack opening displacements and their derivatives as unknown quantities. A collocation method in conjunction with a time-stepping scheme is developed to solve the non-hypersingular time-domain BIEs. To simplify the analysis and to describe the proper behaviour of the unknown quantities at the crack front, a constant spatial shape function is applied for elements away from the crack front, while a spatial ‘square-root’ crack-tip shape function is adopted for elements near the crack front. A linear temporal shape function is used in the time-stepping scheme. Numerical calculations, have been carried out for penny-shaped and square cracks. Results for the elastodynamic stress intensity factors are presented as functions of the temporal and the spatial variables. For the test examples considered, good agreement between the present results and those of other authors is obtained.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
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