Calculated and Measured Ultrasonic Response of an Elastic Cylinder Embedded in an Elastic Medium

itanium metal matrix composite (TMC) materials are fabricated by consolidating alternate layers of suitable titanium foils and silicon carbide fibers. The foils are generally 0.005-0.010 in thick and the fibers have diameters ranging from 0.004 in. to 0.0055 in. Furthermore, the fibers have a core of one material and an outer annular ring of silicon carbide (Fig. 1). The fibers used in the work described here, designated SCS6 fibers, have an outer diameter of 0.0055 in. and an inner carbon core with a diameter of 0.0013 in. During consolidation, the matrix material is heated under pressure so that it flows around the fibers, forming a strong interfacial bond with the fiber and a strong diffusion bond where the adjacent foils come in contact. Several types of defects can occur during the consolidation process. There can be lack of bonding or incomplete bonding between the adjacent foils or between the matrix and the fibers. It is also possible that an undesirable reaction can occur between the fiber and the matrix, producing a brittle zone that will degrade the strength of the material.</p

Interface Effects on Attenuation and Phase Velocities in Metal-Matrix Composites

One often determines the effective elastic moduli and damping of a heterogeneous material by using elastic waves (propagating or standing). Several theoretical studies show that for long wavelengths one can calculate the effective wave speeds of plane longitudinal and shear waves through a composite material. At long wavelengths the wave speeds thus calculated are nondispersive and hence provide the values for the static effective elastic properties. References to some of the recent theoretical and experimental studies can be found in [1–12]. The scattering formulations developed in [1–8] provide a means to obtain both the effective wave speeds and the damping caused by scattering

Structural Analysis of the UBA Domain of X-linked Inhibitor of Apoptosis Protein Reveals Different Surfaces for Ubiquitin-Binding and Self-Association

BACKGROUND: Inhibitor of apoptosis proteins (IAPs) belong to a pivotal antiapoptotic protein family that plays a crucial role in tumorigenesis, cancer progression, chemoresistance and poor patient-survival. X-linked inhibitor of apoptosis protein (XIAP) is a prominent member of IAPs attracting intense research because it has been demonstrated to be a physiological inhibitor of caspases and apoptosis. Recently, an evolutionarily conserved ubiquitin-associated (UBA) domain was identified in XIAP and a number of RING domain-bearing IAPs. This has placed the IAPs in the group of ubiquitin binding proteins. Here, we explore the three-dimensional structure of the XIAP UBA domain (XIAP-UBA) and how it interacts with mono-ubiquitin and diubiquitin conjugates. PRINCIPAL FINDINGS: The solution structure of the XIAP-UBA domain was determined by NMR spectroscopy. XIAP-UBA adopts a typical UBA domain fold of three tightly packed alpha-helices but with an additional N-terminal 3(10) helix. The XIAP-UBA binds mono-ubiquitin as well as Lys48-linked and linear-linked diubiquitins at low-micromolar affinities. NMR analysis of the XIAP-UBA-ubiquitin interaction reveals that it involves the classical hydrophobic patches surrounding Ile44 of ubiquitin and the conserved MGF/LV motif surfaces on XIAP-UBA. Furthermore, dimerization of XIAP-UBA was observed. Mapping of the self-association surface of XIAP-UBA reveals that the dimerization interface is formed by residues in the N-terminal 3(10) helix, helix alpha1 and helix alpha2, separate from the ubiquitin-binding surface. CONCLUSION: Our results provide the first structural information of XIAP-UBA and map its interaction with mono-ubiquitin, Lys48-linked and linear-linked diubiquitins. The notion that XIAP-UBA uses different surfaces for ubiquitin-binding and self-association provides a plausible model to explain the reported selectivity of XIAP in binding polyubiquitin chains with different linkages.published_or_final_versio

Quantitative imaging of concentrated suspensions under flow

We review recent advances in imaging the flow of concentrated suspensions, focussing on the use of confocal microscopy to obtain time-resolved information on the single-particle level in these systems. After motivating the need for quantitative (confocal) imaging in suspension rheology, we briefly describe the particles, sample environments, microscopy tools and analysis algorithms needed to perform this kind of experiments. The second part of the review focusses on microscopic aspects of the flow of concentrated model hard-sphere-like suspensions, and the relation to non-linear rheological phenomena such as yielding, shear localization, wall slip and shear-induced ordering. Both Brownian and non-Brownian systems will be described. We show how quantitative imaging can improve our understanding of the connection between microscopic dynamics and bulk flow.Comment: Review on imaging hard-sphere suspensions, incl summary of methodology. Submitted for special volume 'High Solid Dispersions' ed. M. Cloitre, Vol. xx of 'Advances and Polymer Science' (Springer, Berlin, 2009); 22 pages, 16 fig

Gene Expression in the Rodent Brain is Associated with Its Regional Connectivity

The putative link between gene expression of brain regions and their neural connectivity patterns is a fundamental question in neuroscience. Here this question is addressed in the first large scale study of a prototypical mammalian rodent brain, using a combination of rat brain regional connectivity data with gene expression of the mouse brain. Remarkably, even though this study uses data from two different rodent species (due to the data limitations), we still find that the connectivity of the majority of brain regions is highly predictable from their gene expression levels–the outgoing (incoming) connectivity is successfully predicted for 73% (56%) of brain regions, with an overall fairly marked accuracy level of 0.79 (0.83). Many genes are found to play a part in predicting both the incoming and outgoing connectivity (241 out of the 500 top selected genes, p-value<1e-5). Reassuringly, the genes previously known from the literature to be involved in axon guidance do carry significant information about regional brain connectivity. Surveying the genes known to be associated with the pathogenesis of several brain disorders, we find that those associated with schizophrenia, autism and attention deficit disorder are the most highly enriched in the connectivity-related genes identified here. Finally, we find that the profile of functional annotation groups that are associated with regional connectivity in the rodent is significantly correlated with the annotation profile of genes previously found to determine neural connectivity in C. elegans (Pearson correlation of 0.24, p<1e-6 for the outgoing connections and 0.27, p<1e-5 for the incoming). Overall, the association between connectivity and gene expression in a specific extant rodent species' brain is likely to be even stronger than found here, given the limitations of current data

Identification of Tumor Suppressors and Oncogenes from Genomic and Epigenetic Features in Ovarian Cancer

The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We seek to identify those genetic and epigenetic aberrations that have the most impact on gene function within the tumor. First, we perform a bioinformatic analysis of copy number variation (CNV) and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We separately examined CNV and DNA methylation for 42 primary serous ovarian cancer samples using MOMA-ROMA assays and 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with altered copy number and correlated changes in expression. Among these genes CCNE1, POP4, UQCRB, PHF20L1 and C19orf2 were identified within both data sets. We were specifically interested in copy number variation as our base genomic property in the prediction of tumor suppressors and oncogenes in the altered ovarian tumor. We therefore identify changes in DNA methylation and expression for all amplified and deleted genes. We statistically define tumor suppressor and oncogenic features for these modalities and perform a correlation analysis with expression. We predicted 611 potential oncogenes and tumor suppressors candidates by integrating these data types. Genes with a strong correlation for methylation dependent expression changes exhibited at varying copy number aberrations include CDCA8, ATAD2, CDKN2A, RAB25, AURKA, BOP1 and EIF2C3. We provide copy number variation and DNA methylation analysis for over 11,500 individual genes covering the genetic landscape of ovarian cancer tumors. We show the extent of genomic and epigenetic alterations for known tumor suppressors and oncogenes and also use these defined features to identify potential ovarian cancer gene candidates

Cell-specific microarray profiling experiments reveal a comprehensive picture of gene expression in the C. elegans nervous system

A novel strategy for profiling Caenorhabditis elegans cells identifies transcripts highly enriched in either the embryonic or larval C. elegans nervous system, including 19 conserved transcripts of unknown function that are also expressed in the mammalian brain

The Viral Janus: Viruses as Aetiological Agents and Treatment Options in Colorectal Cancer.

In recent years, our understanding of the importance of microorganisms on and within our bodies has been revolutionized by the ability to characterize entire microbial communities. No more so is this true than in cases of disease. Community studies have revealed strong associations between microbial populations and disease states where such concomitance was previously absent from aetiology: including in cancers. The study of viruses, in particular, has benefited from the development of new community profiling techniques and we are now realising that their prominence within our physiology is nearly as broad as the diversity of the organisms themselves. Here, we examine the relationship between viruses and colorectal cancer (CRC), the leading cause of gastrointestinal cancer-related death worldwide. In CRC, viruses have been suggested to be involved in oncogenesis both directly, through infection of our cells, and indirectly, through modulating the composition of bacterial communities. Interestingly though, these characteristics have also led to their examination from another perspective-as options for treatment. Advances in our understanding of molecular and viral biology have caused many to look at viruses as potential modular biotherapeutics, where deleterious characteristics can be tamed and desirable characteristics exploited. In this article, we will explore both of these perspectives, covering how viral infections and involvement in microbiome dynamics may contribute to CRC, and examine ways in which viruses themselves could be harnessed to treat the very condition their contemporaries may have had a hand in creating