Genomic and functional profiling of gastric cancer

Helicobacter pylori infection is a risk factor for gastric cancer, which is a major health issue worldwide. Gastric cancer has a poor prognosis due to the unnoticeable progression of the disease and surgery is the only available treatment in gastric cancer. Therefore, gastric cancer patients would greatly benefit from identifying biomarker genes that would improve diagnostic and prognostic prediction and provide targets for molecular therapies. DNA copy number amplifications are the hallmarks of cancers in various anatomical locations. Mechanisms of amplification predict that DNA double-strand breaks occur at the margins of the amplified region. The first objective of this thesis was to identify the genes that were differentially expressed in H. pylori infection as well as the transcription factors and signal transduction pathways that were associated with the gene expression changes. The second objective was to identify putative biomarker genes in gastric cancer with correlated expression and copy number, and the last objective was to characterize cancers based on DNA copy number amplifications. DNA microarrays, an in vitro model and real-time polymerase chain reaction were used to measure gene expression changes in H. pylori infected AGS cells. In order to identify the transcription factors and signal transduction pathways that were activated after H. pylori infection, gene expression profiling data from the H. pylori experiments and a bioinformatics approach accompanied by experimental validation were used. Genome-wide expression and copy number microarray analysis of clinical gastric cancer samples and immunohistochemistry on tissue microarray were used to identify putative gastric cancer genes. Data mining and machine learning techniques were applied to study amplifications in a cross-section of cancers. FOS and various stress response genes were regulated by H. pylori infection. H. pylori regulated genes were enriched in the chromosomal regions that are frequently changed in gastric cancer, suggesting that molecular pathways of gastric cancer and premalignant H. pylori infection that induces gastritis are interconnected. 16 transcription factors were identified as being associated with H. pylori infection induced changes in gene expression. NF-κB transcription factor and p50 and p65 subunits were verified using elecrophoretic mobility shift assays. ERBB2 and other genes located in 17q12- q21 were found to be up-regulated in association with copy number amplification in gastric cancer. Cancers with similar cell type and origin clustered together based on the genomic localization of the amplifications. Cancer genes and large genes were co-localized with amplified regions and fragile sites, telomeres, centromeres and light chromosome bands were enriched at the amplification boundaries. H. pylori activated transcription factors and signal transduction pathways function in cellular mechanisms that might be capable of promoting carcinogenesis of the stomach. Intestinal and diffuse type gastric cancers showed distinct molecular genetic profiles. Integration of gene expression and copy number microarray data allowed the identification of genes that might be involved in gastric carcinogenesis and have clinical relevance. Gene amplifications were demonstrated to be non-random genomic instabilities. Cell lineage, properties of precursor stem cells, tissue microenvironment and genomic map localization of specific oncogenes define the site specificity of DNA amplifications, whereas labile genomic features define the structures of amplicons. These conclusions suggest that the definition of genomic changes in cancer is based on the interplay between the cancer cell and the tumor microenvironment.

Developmental and growth controls of tillering and water-soluble carbohydrate accumulation in contrasting wheat (Triticum aestivum L.) genotypes: can we dissect them?

In wheat, tillering and water-soluble carbohydrates (WSCs) in the stem are potential traits for adaptation to different environments and are of interest as targets for selective breeding. This study investigated the observation that a high stem WSC concentration (WSCc) is often related to low tillering. The proposition tested was that stem WSC accumulation is plant density dependent and could be an emergent property of tillering, whether driven by genotype or by environment. A small subset of recombinant inbred lines (RILs) contrasting for tillering was grown at different plant densities or on different sowing dates in multiple field experiments. Both tillering and WSCc were highly influenced by the environment, with a smaller, distinct genotypic component; the genotypeenvironment range covered 350750 stems m(2) and 25210mg g(1) WSCc. Stem WSCc was inversely related to stem number m(2), but genotypic rankings for stem WSCc persisted when RILs were compared at similar stem density. Low tilleringhigh WSCc RILs had similar leaf area index, larger individual leaves, and stems with larger internode cross-section and wall area when compared with high tilleringlow WSCc RILs. The maximum number of stems per plant was positively associated with growth and relative growth rate per plant, tillering rate and duration, and also, in some treatments, with leaf appearance rate and final leaf number. A common threshold of the red:far red ratio (0.390.44; standard error of the difference0.055) coincided with the maximum stem number per plant across genotypes and plant densities, and could be effectively used in crop simulation modelling as a ocut-off' rule for tillering. The relationship between tillering, WSCc, and their component traits, as well as the possible implications for crop simulation and breeding, is discussed.

Design and assessment of weirs for fish passage under drowned conditions

In aquatic systems, in-stream structures such as dams, weirs and road crossings can act as barriers to fish movement along waterways. There is a growing array of technological fish-pass solutions for the movement of fish across large structures such as weirs and dams. However, most existing weir structures lack dedicated fishways, and fish often have to rely on drowned conditions to move upstream. In order to assess the adequacy of a given or proposed weir for upstream fish passage under drowned conditions, it is necessary to determine, firstly, the hydraulic properties of the drowned weir with respect to the requirements of the fish community and, secondly, the duration and timing of drowning flows with respect to the hydrograph for the site and the likely timing of fish movements. This paper primarily addresses the first issue. A computer program has been developed and incorporated in a simple-to-operate spreadsheet for the determination of the hydraulic characteristics of a drowned weir which are important to fish movement. The program is based on a theoretical analysis of drowned weirs and subsequent extensive verification in laboratory experiments. Inputs to the program include site information comprising channel cross-section data, channel slope, and channel roughness, and weir information comprising weir height and the required minimum drowned depth over the weir for migrating fish passage. The program then calculates the flow rate at which the required level of drowning occurs, the velocity characteristics above the weir (including transverse distributions), and flow depths and velocities upstream and downstream of the weir. The paper discusses (briefly) the theoretical background of the program and its experimental verification. A case study is then presented that illustrates the use of the program in the field to assess fish passage opportunities at an existing weir and to develop a case for retrofitting a fishway. Some discussion is also provided on the contribution of a modelled drownout volume to the assessment of how significant a barrier a weir is to fish passage. It is shown that the program is an important new additional tool in the assessment of the adequacy of weir structures in providing for fish movement and informing associated fish passage solutions. (C) 2011 Elsevier B.V. All rights reserved.

Water-ethanol mixtures by molecular dynamics and x-ray Compton scattering

Water-ethanol mixtures are commonly used in industry and house holds. However, quite surprisingly their molecular-level structure is still not completely understood. In particular, there is evidence that the local intermolecular geometries depend significantly on the concentration. The aim of this study was to gain information on the molecular-level structures of water-ethanol mixtures by two computational methods. The methods are classical molecular dynamics (MD), where the movement of molecules can be studied, and x-ray Compton scattering, in which the scattering cross section is sensitive to the electron momentum density. Firstly, the water-ethanol mixtures were studied with MD simulations, with the mixture concentration ranging from 0 to 100%. For the simulations well-established force fields were used for the water and ethanol molecules (TIP4P and OPLS-AA, respectively). Moreover, two models were used for ethanol, rigid and non-rigid. In the rigid model the intramolecular bond lengths are fixed, whereas in the non-rigid model the lengths are determined by harmonic potentials. Secondly, mixtures with three different concentrations employing both ethanol models were studied by calculating the experimentally observable x-ray quantity, the Compton profile. In the MD simulations a slight underestimation in the density was observed as compared to experiment. Furthermore, a positive excess of hydrogen bonding with water molecules and a negative one with ethanol was quantified. Also, the mixture was found more structured when the ethanol concentration was higher. Negligible differences in the results were found between the two ethanol models. In contrast, in the Compton scattering results a notable difference between the ethanol models was observed. For the rigid model the Compton profiles were similar for all the concentrations, but for the non-rigid model they were distinct. This leads to two possibilities of how the mixing occurs. Either the mixing is similar in all concentrations (as suggested by the rigid model) or the mixing changes for different concentrations (as suggested by the non-rigid model). Either way, this study shows that the choice of the force field is essential in the microscopic structure formation in the MD simulations. When the sources of uncertainty in the calculated Compton profiles were analyzed, it was found that more statistics needs to be collected to reduce the statistical uncertainty in the final results. The obtained Compton scattering results can be considered somewhat preliminary, but clearly indicative of the behaviour of the water-ethanol mixtures when the force field is modified. The next step is to collect more statistics and compare the results with experimental data to decide which ethanol model describes the mixture better. This way, valuable information on the microscopic structure of water-ethanol mixtures can be found. In addition, information on the force fields in the MD simulations and on the ability of the MD simulations to reproduce the microscopic structure of binary liquids is obtained.

Properties of the gold related acceptor level in silicon

The apparent thermal activation energy of 0.56 eV and the electron thermal capture cross section of 2.0 × 10-16 cm2 are measured for the gold related acceptor level in p+ nn+ silicon diodes by isothermal current transient and DLTS techniques. Using the emission and capture rate data and a degeneracy ratio of 2, the energy separation of the trap level from the conduction band is calculated and found to have the same temperature dependence as the band gap indicating that the acceptor level is pinned with respect to the valence band a t Ev + 0.637 eV.

Inelastic Postbuckling of Columns of Variable Flexural Rigidity

Effects of large deformation and inelasticity are considered in formulating the behavior of columns of variable cross section subjected to an axial compressive load. Simple, approximate methods are used to obtain numerical results. The combined effect of the nonlinearities is shown to be of a hardening type for small column deflections

Dynamic Instabilities in Slender Space Launch Vehicles under Propulsive Thrust and Aerodynamic Forces

A mechanics based linear analysis of the problem of dynamic instabilities in slender space launch vehicles is undertaken. The flexible body dynamics of the moving vehicle is studied in an inertial frame of reference, including velocity induced curvature effects, which have not been considered so far in the published literature. Coupling among the rigid-body modes, the longitudinal vibrational modes and the transverse vibrational modes due to asymmetric lifting-body cross-section are considered. The model also incorporates the effects of aerodynamic forces and the propulsive thrust of the vehicle. The effects of the coupling between the combustion process (mass variation, developed thrust etc.) and the variables involved in the flexible body dynamics (displacements and velocities) are clearly brought out. The model is one-dimensional, and it can be employed to idealised slender vehicles with complex shapes. Computer simulations are carried out using a standard eigenvalue problem within h-p finite element modelling framework. Stability regimes for a vehicle subjected to propulsive thrust are validated by comparing the results from published literature. Numerical simulations are carried out for a representative vehicle to determine the instability regimes with vehicle speed and propulsive thrust as the parameters. The phenomena of static instability (divergence) and dynamic instability (flutter) are observed. The results at low Mach number match closely with the results obtained from previous models published in the literature.

Experimental investigation of catalytic and non-catalytic surface reactions on SiO2 thin films with shock heated oxygen gas

The present study is to investigate the interaction of strong shock heated oxygen on the surface of SiO2 thin film. The thermally excited oxygen undergoes a three-body recombination reaction on the surface of silicon dioxide film. The different oxidation states of silicon species on the surface of the shock-exposed SiO2 film are discussed based on X-ray Photoelectron Spectroscopy (XPS) results. The surface morphology of the shock wave induced damage at the cross section of SiO2 film and structure modification of these materials are analyzed using scanning electron microscopy and ion microscopy. Whether the surface reaction of oxygen on SiO2 film is catalytic or non-catalytic is discussed in this paper.

The role of triplet states in the emission mechanism of polymer light-emitting diodes

The blue emission of polyfluorene (PF)-based light-emitting diodes (LEDs) is known to degrade due to a low-energy green emission, which hitherto has been attributed to oxidative defects. By studying the electroluminescence (EL) from ethyl-hexyl substituted PF LEDs in the presence of oxygen and in an inert atmosphere, and by using trace quantities of paramagnetic impurities (PM) in the polymer, we show that the triplet states play a major role in the low-energy emission mechanism. Our time-dependent many-body studies show a large cross-section for the triplet formation in the EL process in the presence of PM, primarily due to electron-hole recombination processes.

Non-linear vibrations of non-unifo with concentrated masses

Large amplitude oscillations of cantilevered beams of variable cross-section, with concentrated masses along the span, are studied in this paper. The governing non-linear ordinary differential equation is solved by an averaging technique to obtain approximate solutions. Stability boundaries of the response are also investigated.

Flow Studies in Non Circular Tubes with Wall Injection

An analysis of inviscid incompressible flow in a tube of sinusoidally perturbed circular cross section with wall injection has been made. The velocity and pressure fields have been obtained. Measurements of axial velocity profiles and pressure distribution have been made in a simulated star shaped tube with wall injection. The static pressure at the star recess is found to be more than that at the star point, this feature being in conformity with the analytical result. Flow visualisation by photography of injected smoke seems to show simple diffusion rather than strong vortices in the recess.

Qed On The Groenewold-Moyal Plane

We investigate a version of noncommutative QED where the interaction term, although natural, breaks the spin-statistics connection. We calculate e(-) + e(-) -> e(-) + e(-) and gamma + e(-) -> gamma + e(-) cross-sections in the tree approximation and explicitly display their dependence on theta(mu nu). Remarkably the zero of the elastic e(-) + e(-) -> e(-) + e(-) cross-section at 90 degrees in the center-of-mass system, which is due to Pauli principle, is shifted away as a function of theta(mu nu) and energy.

A comparative molecular dynamics study of diffusion of n-decane and 3-methyl pentane in Y zeolite

Molecular dynamics simulations are reported on the structure and dynamics of n-decane and 3-methylpentane in zeolite NaY. We have calculated several properties such as the center of mass-center of mass rdf, the end-end distance distribution, bond angle distribution and dihedral angle distribution. We have also analysed trajectory to obtain diffusivity and velocity autocorrelation function (VACF). Surprisingly, the diffusivity of 3-methylpentane which is having larger cross-section perpendicular to the long molecular axis is higher than n-decane at 300 K. Activation energies have been obtained from simulations performed at 200 K, 300 K, 350 K, 400 K and 450 K in the NVE ensemble. These results can be understood in terms of the previously known levitation effect. Arrhenious plot has higher value of slope for n-decane (5 center dot 9 kJ/mol) than 3-methylpentane (3 center dot 7 kJ/mol) in agreement with the prediction of levitation effect.

A fluctuation-based characterization of athermal phase transitions:Application to shape memory alloys

We employ a fluctuation-based technique to investigate the athermal component associated with martensite phase transition, which is a prototype of temperature-driven structural transformation. Statistically, when the phase transition is purely athermal, we find that the temporal sequence of avalanches under constant drive is insensitive to the drive rate. We have used fluctuations in electrical resistivity or noise in nickel titanium shape memory alloys in three different forms: a thin film exhibiting well-defined transition temperatures,a highly disordered film, and a bulk wire of rectangular cross-section. Noise is studied in the realm of dynamic transition,viz.while the temperature is being ramped, which probes into the kinetics of the transformation at real time scales,and could probably stand out as a promising tool for material testing in various other systems, including nanoscale devices.

Shape effect on optimal geometric conditions in surface aeration systems

The performance of surface aeration systems, among other key design variables, depends upon the geometric parameters of the aeration tank. Efficient performance and scale up or scale down of the experimental results of an aeration ystem requires optimal geometric conditions. Optimal conditions refer to the conditions of maximum oxygen transfer rate, which assists in scaling up or down the system for ommercial utilization. The present work investigates the effect of an aeration tank's shape (unbaffled circular, baffled circular and unbaffled square) on oxygen transfer. Present results demonstrate that there is no effect of shape on the optimal geometric conditions for rotor position and rotor dimensions. This experimentation shows that circular tanks (baffled or unbaffled) do not have optimal geometric conditions for liquid transfer, whereas the square cross-section tank shows a unique geometric shape to optimize oxygen transfer.