Semi-analytical hybrid approach for modelling wave motion excited by a piezoelectric transducer in a laminate with multiple cracks

A semi-analytical hybrid approach is presented here to simulate the dynamic behaviour of a multi-layered elastic waveguide with a system of delaminations and a piezoelectric transducer mounted on the surface of the waveguide. The proposed hybrid approach combines the advantages of the frequency domain spectral element method, which is applied to discretize a complex-shaped piezoelectric structure, and the boundary integral equation method employed to simulate wave propagation in multi-layered waveguide with multiple delaminations. The proposed method is applicable to the multi-parameter analysis of the phenomena related to elastic wave scattering and excitation. The advantages of the presented extended semi-analytical hybrid approach method along with the results of the parametric analysis of wave propagation in the considered structures are discussed

Integrative Genome Comparison of Primary and Metastatic Melanomas

A cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progression-associated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC), to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes

Endothelin-1 Inhibits Prolyl Hydroxylase Domain 2 to Activate Hypoxia-Inducible Factor-1α in Melanoma Cells

The endothelin B receptor (ET(B)R) promotes tumorigenesis and melanoma progression through activation by endothelin (ET)-1, thus representing a promising therapeutic target. The stability of hypoxia-inducible factor (HIF)-1alpha is essential for melanomagenesis and progression, and is controlled by site-specific hydroxylation carried out by HIF-prolyl hydroxylase domain (PHD) and subsequent proteosomal degradation.Here we found that in melanoma cells ET-1, ET-2, and ET-3 through ET(B)R, enhance the expression and activity of HIF-1alpha and HIF-2alpha that in turn regulate the expression of vascular endothelial growth factor (VEGF) in response to ETs or hypoxia. Under normoxic conditions, ET-1 controls HIF-alpha stability by inhibiting its degradation, as determined by impaired degradation of a reporter gene containing the HIF-1alpha oxygen-dependent degradation domain encompassing the PHD-targeted prolines. In particular, ETs through ET(B)R markedly decrease PHD2 mRNA and protein levels and promoter activity. In addition, activation of phosphatidylinositol 3-kinase (PI3K)-dependent integrin linked kinase (ILK)-AKT-mammalian target of rapamycin (mTOR) pathway is required for ET(B)R-mediated PHD2 inhibition, HIF-1alpha, HIF-2alpha, and VEGF expression. At functional level, PHD2 knockdown does not further increase ETs-induced in vitro tube formation of endothelial cells and melanoma cell invasiveness, demonstrating that these processes are regulated in a PHD2-dependent manner. In human primary and metastatic melanoma tissues as well as in cell lines, that express high levels of HIF-1alpha, ET(B)R expression is associated with low PHD2 levels. In melanoma xenografts, ET(B)R blockade by ET(B)R antagonist results in a concomitant reduction of tumor growth, angiogenesis, HIF-1alpha, and HIF-2alpha expression, and an increase in PHD2 levels.In this study we identified the underlying mechanism by which ET-1, through the regulation of PHD2, controls HIF-1alpha stability and thereby regulates angiogenesis and melanoma cell invasion. These results further indicate that targeting ET(B)R may represent a potential therapeutic treatment of melanoma by impairing HIF-1alpha stability

The neutron and its role in cosmology and particle physics

Experiments with cold and ultracold neutrons have reached a level of precision such that problems far beyond the scale of the present Standard Model of particle physics become accessible to experimental investigation. Due to the close links between particle physics and cosmology, these studies also permit a deep look into the very first instances of our universe. First addressed in this article, both in theory and experiment, is the problem of baryogenesis ... The question how baryogenesis could have happened is open to experimental tests, and it turns out that this problem can be curbed by the very stringent limits on an electric dipole moment of the neutron, a quantity that also has deep implications for particle physics. Then we discuss the recent spectacular observation of neutron quantization in the earth's gravitational field and of resonance transitions between such gravitational energy states. These measurements, together with new evaluations of neutron scattering data, set new constraints on deviations from Newton's gravitational law at the picometer scale. Such deviations are predicted in modern theories with extra-dimensions that propose unification of the Planck scale with the scale of the Standard Model ... Another main topic is the weak-interaction parameters in various fields of physics and astrophysics that must all be derived from measured neutron decay data. Up to now, about 10 different neutron decay observables have been measured, much more than needed in the electroweak Standard Model. This allows various precise tests for new physics beyond the Standard Model, competing with or surpassing similar tests at high-energy. The review ends with a discussion of neutron and nuclear data required in the synthesis of the elements during the "first three minutes" and later on in stellar nucleosynthesis.Comment: 91 pages, 30 figures, accepted by Reviews of Modern Physic

SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b

BACKGROUND: The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes several unique group specific accessory proteins with unknown functions. Among them, accessory protein 3b (also known as ORF4) was lately identified as one of the viral interferon antagonist. Recently our lab uncovered a new role for 3b in upregulation of AP-1 transcriptional activity and its downstream genes. Thus, we believe that 3b might play an important role in SARS-CoV pathogenesis and therefore is of considerable interest. The current study aims at identifying novel host cellular interactors of the 3b protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using yeast two-hybrid and co-immunoprecipitation techniques, we have identified a host transcription factor RUNX1b (Runt related transcription factor, isoform b) as a novel interacting partner for SARS-CoV 3b protein. Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. Kinase assay and pharmacological inhibitor treatment implied that 3b also affect RUNX1b transcriptional activity by regulating its ERK dependent phosphorylation levels. Additionally, mRNA levels of MIP-1α, a RUNX1b target gene upregulated in SARS-CoV infected monocyte-derived dendritic cells, were found to be elevated in 3b expressing U937 monocyte cells. CONCLUSIONS/SIGNIFICANCE: These results unveil a novel interaction of SARS-CoV 3b with the host factor, RUNX1b, and speculate its physiological relevance in upregulating cytokines and chemokine levels in state of SARS virus infection

Analysis of Eigenfrequencies of a Circular Interface Delamination in Elastic Media Based on the Boundary Integral Equation Method

The widespread of composite structures demands efficient numerical methods for the simulation dynamic behaviour of elastic laminates with interface delaminations with interacting faces. An advanced boundary integral equation method employing the Hankel transform of Green’s matrices is proposed for modelling wave scattering and analysis of the eigenfrequencies of interface circular partially closed delaminations between dissimilar media. A more general case of partially closed circular delamination is introduced using the spring boundary conditions with non-uniform spring stiffness distribution. The unknown crack opening displacement is expanded as Fourier series with respect to the angular coordinate and in terms of associated Legendre polynomials of the first kind via the radial coordinate. The problem is decomposed into a system of boundary integral equations and solved using the Bubnov-Galerkin method. The boundary integral equation method is compared with the meshless method and the published works for a homogeneous space with a circular open crack. The results of the numerical analysis showing the efficiency and the convergence of the method are demonstrated. The proposed method might be useful for damage identification employing the information on the eigenfrequencies estimated experimentally. Also, it can be extended for multi-layered composites with imperfect contact between sub-layers and multiple circular delaminations

Analysis of Eigenfrequencies of a Circular Interface Delamination in Elastic Media Based on the Boundary Integral Equation Method

The widespread of composite structures demands efficient numerical methods for the simulation dynamic behaviour of elastic laminates with interface delaminations with interacting faces. An advanced boundary integral equation method employing the Hankel transform of Green’s matrices is proposed for modelling wave scattering and analysis of the eigenfrequencies of interface circular partially closed delaminations between dissimilar media. A more general case of partially closed circular delamination is introduced using the spring boundary conditions with non-uniform spring stiffness distribution. The unknown crack opening displacement is expanded as Fourier series with respect to the angular coordinate and in terms of associated Legendre polynomials of the first kind via the radial coordinate. The problem is decomposed into a system of boundary integral equations and solved using the Bubnov-Galerkin method. The boundary integral equation method is compared with the meshless method and the published works for a homogeneous space with a circular open crack. The results of the numerical analysis showing the efficiency and the convergence of the method are demonstrated. The proposed method might be useful for damage identification employing the information on the eigenfrequencies estimated experimentally. Also, it can be extended for multi-layered composites with imperfect contact between sub-layers and multiple circular delaminations

Chalmers Publication Library Interface damage modeled by spring boundary conditions for in-plane elastic waves Interface damage modeled by spring boundary conditions for in-plane elastic waves

Abstract In-plane elastic wave propagation in the presence of a damaged interface is investigated. The damage is modeled as a distribution of small cracks and this is transformed into a spring boundary condition. First the scattering by a single interface crack is determined explicitly in the low frequency limit for the case of a plane wave normally incident to the interface. The transmission at an interface with a random distribution of small cracks is then determined and is compared to periodically distributed cracks. The cracked interface is then described by a distributed spring boundary condition. As an illustration the dispersion relation of the first modes in a thick plate with a damaged interface in the middle is given

Elastodynamic Behaviour of Laminate Structures with Soft Thin Interlayers: Theory and Experiment

Laminate structures composed of stiff plates and thin soft interlayers are widely used in aerospace, automotive and civil engineering encouraging the development of reliable non-destructive strategies for their condition assessment. In the paper, elastodynamic behaviour of such laminate structures is investigated with emphasis on its application in ultrasonic based NDT and SHM for the identification of interlayer mechanical and interfacial contact properties. A particular attention is given to the practically important frequency range, in which the wavelength considerably exceeds the thickness of the film. Three layer model with spring-type boundary conditions employed for imperfect contact simulation is used for numerical investigation. Novel effective boundary conditions are derived via asymptotic expansion technique and used for analysis of the peculiar properties of elastic guided waves in considered laminates. It is revealed that the thin and soft film influences the behaviour of the laminate mainly via the effective stiffnesses being a combination of the elastic moduli of the film, its thickness and interface stiffnesses. To evaluate each of these parameters separately (or to figure out that the available experimental data are insufficient), a step-wise procedure employing the effective boundary conditions is proposed and tested versus the laser Doppler vibrometry data for Lamb waves in Aluminium/Polymer film/Alumunium structure. A good agreement between theoretical and experimental data is demonstrated for a certain symmetric laminate specimen. The possibility of using film-related thickness resonance frequencies to estimate the film properties and contact quality is also demonstrated. Additionally, the rich family of edge waves is also investigated, and the splitting of fundamental edge waves into pairs is revealed