Dynamic analysis of shell structures with application to blast resistant doors

Shock and Vibration104269-279SHVI

Open Inflation With Scalar-tensor Gravity

The open inflation model recently proposed by Hawking and Turok is investigated in scalar-tensor gravity context. If the dilaton-like field has no potential, the instanton of our model is singular but has a finite action. The Gibbons-Hawking surface term vanishes and hence, can not be used to make $\Omega_0$ nonzero. To obtain a successful open inflation one should introduce other matter fields or a potential for the dilaton-like fields.Comment: 10 pages.1 figure. Some comments and references are improved. to be published in PR

Shared-Memory parallelization of consistent particle method for violent wave impact problems

A shared-memory parallelization is implemented to the recently developed Consistent Particle Method (CPM) for violent wave impact problems. The advantages of this relatively new particle method lie in four key aspects: (1) accurate computation of Laplacian and gradient operators based on Taylor series expansion, alleviating spurious pressure fluctuation and being able to model two-phase flows characterized by large density difference, (2) a thermodynamics-based compressible solver for modelling compressible air that eliminates the need of determining artificial sound speed, (3) seamless coupling of the compressible air solver and incompressible water solver, and (4) parallelization of the numerical model based on Open Multi-Processing (OpenMP) and a parallel direct sparse solver (Pardiso) to significantly improve computational efficiency. Strong and weak scaling analyses of the parallelized CPM are conducted, showing an efficiency speedup of 100 times or more depending on the size of simulated problem. To demonstrate the accuracy of the developed numerical model, three numerical examples are studied including the benchmark study of wave impact on seawall, and our experimental studies of violent water sloshing under rotational excitations and sloshing impact with entrapped air pocket. CPM is shown to accurately capture highly deformed breaking waves and violent wave impact pressure including pressure oscillation induced by air cushion effect

Observational constraints on Horava-Lifshitz cosmology

We use observational data from Type Ia Supernovae (SNIa), Baryon Acoustic Oscillations (BAO), and Cosmic Microwave Background (CMB), along with requirements of Big Bang Nucleosynthesis (BBN), to constrain the cosmological scenarios governed by Horava-Lifshitz gravity. We consider both the detailed and non-detailed balance versions of the gravitational sector, and we include the matter and radiation sectors. We conclude that the detailed-balance scenario cannot be ruled out from the observational point of view, however the corresponding likelihood contours impose tight constraints on the involved parameters. The scenario beyond detailed balance is compatible with observational data, and we present the corresponding stringent constraints and contour-plots of the parameters. Although this analysis indicates that Horava-Lifshitz cosmology can be compatible with observations, it does not enlighten the discussion about its possible conceptual and theoretical problems.Comment: 11 pages, 6 figures, version published in JCA

NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts

Cancer stem cells (CSCs) are thought to be critical for the engraftment and long-term growth of many tumors, including glioblastoma (GBM). The cells are at least partially spared by traditional chemotherapies and radiation therapies, and finding new treatments that can target CSCs may be critical for improving patient survival. It has been shown that the NOTCH signaling pathway regulates normal stem cells in the brain, and that GBMs contain stem-like cells with higher NOTCH activity. We therefore used low-passage and established GBM-derived neurosphere cultures to examine the overall requirement for NOTCH activity, and also examined the effects on tumor cells expressing stem cell markers. NOTCH blockade by gamma-secretase inhibitors (GSIs) reduced neurosphere growth and clonogenicity in vitro, whereas expression of an active form of NOTCH2 increased tumor growth. The putative CSC markers CD133, NESTIN, BMI1, and OLIG2 were reduced following NOTCH blockade. When equal numbers of viable cells pretreated with either vehicle (dimethyl sulfoxide) or GSI were injected subcutaneously into nude mice, the former always formed tumors, whereas the latter did not. In vivo delivery of GSI by implantation of drug-impregnated polymer beads also effectively blocked tumor growth, and significantly prolonged survival, albeit in a relatively small cohort of animals. We found that NOTCH pathway inhibition appears to deplete stem-like cancer cells through reduced proliferation and increased apoptosis associated with decreased AKT and STAT3 phosphorylation. In summary, we demonstrate that NOTCH pathway blockade depletes stem-like cells in GBMs, suggesting that GSIs may be useful as chemotherapeutic reagents to target CSCs in malignant gliomas

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Detectable clonal mosaicism and its relationship to aging and cancer

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 × 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 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases