Genomic alterations in primary gastric adenocarcinomas correlate with clinicopathological characteristics and survival.

Background & aimsPathogenesis of gastric cancer is driven by an accumulation of genetic changes that to a large extent occur at the chromosomal level. In order to investigate the patterns of chromosomal aberrations in gastric carcinomas, we performed genome-wide microarray based comparative genomic hybridisation (microarray CGH). With this recently developed technique chromosomal aberrations can be studied with high resolution and sensitivity.MethodsArray CGH was applied to a series of 35 gastric adenocarcinomas using a genome-wide scanning array with 2275 BAC and P1 clones spotted in triplicate. Each clone contains at least one STS for linkage to the sequence of the human genome. These arrays provide an average resolution of 1.4 Mb across the genome. DNA copy number changes were correlated with clinicopathological tumour characteristics as well as survival.ResultsAll thirty-five cancers showed chromosomal aberrations and 16 of the 35 tumours showed one or more amplifications. The most frequent aberrations are gains of 8q24.2, 8q24.1, 20q13.12, 20q13.2, 7p11.2, 1q32.3, 8p23.1-p23.3, losses of 5q14.1, 18q22.1, 19p13.12-p13.3, 9p21.3-p24.3, 17p13.1-p13.3, 13q31.1, 16q22.1, 21q21.3, and amplifications of 7q21-q22, and 12q14.1-q21.1. These aberrations were correlated to clinicopathological characteristics and survival. Gain of 1q32.3 was significantly correlated with lymph node status (p=0.007). Tumours with loss of 18q22.1, as well as tumours with amplifications were associated with poor survival (p=0.02, both).ConclusionsMicroarray CGH has revealed several chromosomal regions that have not been described before in gastric cancer at this frequency and resolution, such as amplification of at 7q21-q22 and 12q14.1-q21.1, as well gains at 1q32.3, 7p11.2, and losses at 13q13.1. Interestingly, gain of 1q32.3 and loss of 18q22.1 are associated with a bad prognosis indicating that these regions could harbour gene(s) that may determine aggressive tumour behaviour and poor clinical outcome

Root branching affects the mobilisation of root-reinforcement in direct shear

The contribution of roots to the mechanical behaviour of soil has typically only been studied for the ultimate limit state. In these approaches, roots are typically modelled as straight and unbranched structures. This approach overlooks the fact that roots may have to deform significantly to mobilise their strength, a process that will be influenced by root architecture effects such as branching, amongst others. Sequential mobilisation of roots affects the peak root-reinforcement, thus differences in mobilisation are important to consider when quantifying root-reinforcement. In this paper, the effect of root branching was modelled using a large-deformation Euler-Bernoulli beam-spring model. The effect of soil was incorporated using non-linear springs, similar to p-y and t-z theory used for foundation piles. By connecting multiple beams together (i.e. applying appropriate linked boundary conditions at root connection points) the effect of branching could be analysed. A soil displacement profile corresponding with direct shear loading was then imposed and the response of the root analysed. It was shown that adding branches led to a quicker mobilisation of root-reinforcement. Branches increased the axial resistance to root displacement and changed the shape of the deformed roots. The presence of branching counteracted root slippage, and thus increased reinforcement. Larger branching densities increased this effect. This analysis demonstrated that the architecture of the root system has a strong effect on the mobilisation of root strength, which directly affects the maximum amount of reinforcement the roots will provide. Future modelling of root-reinforcement, both at the ultimate and serviceable limit state, should account for this effect

BAC to the future! or oligonucleotides: a perspective for micro array comparative genomic hybridization (array CGH)

The array CGH technique (Array Comparative Genome Hybridization) has been developed to detect chromosomal copy number changes on a genome-wide and/or high-resolution scale. It is used in human genetics and oncology, with great promise for clinical application. Until recently primarily PCR amplified bacterial artificial chromosomes (BACs) or cDNAs have been spotted as elements on the array. The large-scale DNA isolations or PCR amplifications of the large-insert clones necessary for manufacturing the arrays are elaborate and time-consuming. Lack of a high-resolution highly sensitive (commercial) alternative has undoubtedly hindered the implementation of array CGH in research and diagnostics. Recently, synthetic oligonucleotides as arrayed elements have been introduced as an alternative substrate for array CGH, both by academic institutions as well as by commercial providers. Oligonucleotide libraries or ready-made arrays can be bought off-the-shelf saving considerable time and efforts. For RNA expression profiling, we have seen a gradual transition from in-house printed cDNA-based expression arrays to oligonucleotide arrays and we expect a similar transition for array CGH. This review compares the different platforms and will attempt to shine a light on the ‘BAC to the future’ of the array CGH technique

Modelling of stress transfer in root-reinforced soils informed by four-dimensional X-ray computed tomography and digital volume correlation data

Vegetation enhances soil shearing resistance through water uptake and root reinforcement. Analytical models for soils reinforced with roots rely on input parameters that are difficult to measure, leading to widely varying predictions of behaviour. The opaque heterogeneous nature of rooted soils results in complex soil-root interaction mechanisms that cannot easily be quantified. The authors measured, for the first time, the shear resistance and deformations of fallow, willow-rooted, and gorse-rooted soils during direct shear using X-ray computed tomography and digital volume correlation. Both species caused an increase in shear zone thickness, both initially and as shear progressed. Shear zone thickness peaked at up to 35 mm, often close to the thickest roots and towards the centre of the column. Root extension during shear was 10-30% less than the tri-linear root profile assumed in a Waldron-type model, owing to root curvature. Root analogues used to explore the root-soil interface behaviour suggested that root lateral branches play an important role in anchoring the roots. The Waldron-type model was modified to incorporate non-uniform shear zone thickness and growth, and accurately predicted the observed, up to seven-fold, increase in shear resistance of root-reinforced soil

The radiative lifetime of metastable CO (a3Π,v=0a^3\Pi, v=0)

We present a combined experimental and theoretical study on the radiative lifetime of CO in the $a^3\Pi_{1,2}, v=0$ state. CO molecules in a beam are prepared in selected rotational levels of this metastable state, Stark-decelerated and electrostatically trapped. From the phosphorescence decay in the trap, the radiative lifetime is measured to be $2.63\pm0.03$ ms for the $a^3\Pi_1, v=0, J=1$ level. From spin-orbit coupling between the $a^3\Pi$ and the $A^1\Pi$ state a 20% longer radiative lifetime of 3.16 ms is calculated for this level. It is concluded that coupling to other $^1\Pi$ states contributes to the observed phosphorescence rate of metastable CO.Comment: replaced with final version, added journal referenc

CGHpower: exploring sample size calculations for chromosomal copy number experiments

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