Tensile Decohesion by Local Failure Criteria

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Non-specific filtering of beta-distributed data.

BackgroundNon-specific feature selection is a dimension reduction procedure performed prior to cluster analysis of high dimensional molecular data. Not all measured features are expected to show biological variation, so only the most varying are selected for analysis. In DNA methylation studies, DNA methylation is measured as a proportion, bounded between 0 and 1, with variance a function of the mean. Filtering on standard deviation biases the selection of probes to those with mean values near 0.5. We explore the effect this has on clustering, and develop alternate filter methods that utilize a variance stabilizing transformation for Beta distributed data and do not share this bias.ResultsWe compared results for 11 different non-specific filters on eight Infinium HumanMethylation data sets, selected to span a variety of biological conditions. We found that for data sets having a small fraction of samples showing abnormal methylation of a subset of normally unmethylated CpGs, a characteristic of the CpG island methylator phenotype in cancer, a novel filter statistic that utilized a variance-stabilizing transformation for Beta distributed data outperformed the common filter of using standard deviation of the DNA methylation proportion, or its log-transformed M-value, in its ability to detect the cancer subtype in a cluster analysis. However, the standard deviation filter always performed among the best for distinguishing subgroups of normal tissue. The novel filter and standard deviation filter tended to favour features in different genome contexts; for the same data set, the novel filter always selected more features from CpG island promoters and the standard deviation filter always selected more features from non-CpG island intergenic regions. Interestingly, despite selecting largely non-overlapping sets of features, the two filters did find sample subsets that overlapped for some real data sets.ConclusionsWe found two different filter statistics that tended to prioritize features with different characteristics, each performed well for identifying clusters of cancer and non-cancer tissue, and identifying a cancer CpG island hypermethylation phenotype. Since cluster analysis is for discovery, we would suggest trying both filters on any new data sets, evaluating the overlap of features selected and clusters discovered

Sperm competition in the scorpionfly <i>Panorpa communis</i> (Mecoptera, Insecta)

The aim of the present study was to investigate the basal mechanism of sperm competition in the European scorpionfly Panorpa communis. Within three laboratory experiments, I used five newly developed microsatellite markers to detect the mechanism of sperm competition in the scorpionfly P. communis. In general, sperm competition occurs if sperm of different males compete for the fertilisation of the ova of one female. As P. communis females mate multiple with different males and store sperm in a storage organ until fertilisation, there is sperm competition in this species. To clarify the outcome of sperm competition, paternity detection of offspring of a multiple mated female is necessary. The most practicable way for paternity detection is the application of microsatellite markers. As a first step of my work, I established five new markers to achieve species specific microsatellites for P. communis. Then, I arranged two experiments in order to detect the mechanism of sperm competition, Here, females were paired to two or three different males, respectively. Since copulation duration, generally, is known to be a good estimator for the number of transferred sperm, I was able to draw conclusions from the proportion of sperm a male contributed to the spermatheca of the female in relation to rival males. I was able to show that the outcome of sperm competition is not influenced by the mating order of males. Consequently, any form of last male sperm precedence for P. communis could be excluded. But, paternity patterns were influenced by copulation duration and therefore by the proportion of sperm represented in the spermatheca. Both experiments conclude that, in P. communis, sperm of different males is mixed and compete numerically for fertilisations, i.e. there is a fair raffle in sperm competition. In a further experiment, I analysed if sperm transfer rates of different males are equal. Although, males were slightly different respective their sperm transfer rates, these differences did not influence the outcome of sperm competition. Accordingly, using copulation duration as a general estimator for the number of transferred sperm is possible. Finally, I discussed the role of sperm competition for scorpionflies in general and, how it may be maintained in this group. Furthermore, I hypothesised how the remarkable mating system in combination with different sperm competition mechanisms in scorpionflies may have evolved

Fiber-diffraction Interferometer using Coherent Fiber Optic Taper

We present a fiber-diffraction interferometer using a coherent fiber optic taper for optical testing in an uncontrolled environment. We use a coherent fiber optic taper and a single-mode fiber having thermally-expanded core. Part of the measurement wave coming from a test target is condensed through a fiber optic taper and spatially filtered from a single-mode fiber to be reference wave. Vibration of the cavity between the target and the interferometer probe is common to both reference and measurement waves, thus the interference fringe is stabilized in an optical way. Generation of the reference wave is stable even with the target movement. Focus shift of the input measurement wave is desensitized by a coherent fiber optic taper

Strain Modulations as a Mechanism to Reduce Stress Relaxation in Laryngeal Tissues

Vocal fold tissues in animal and human species undergo deformation processes at several types of loading rates: a slow strain involved in vocal fold posturing (on the order of 1 Hz or so), cyclic and faster posturing often found in speech tasks or vocal embellishment (1–10 Hz), and shear strain associated with vocal fold vibration during phonation (100 Hz and higher). Relevant to these deformation patterns are the viscous properties of laryngeal tissues, which exhibit non-linear stress relaxation and recovery. In the current study, a large strain time-dependent constitutive model of human vocal fold tissue is used to investigate effects of phonatory posturing cyclic strain in the range of 1 Hz to 10 Hz. Tissue data for two subjects are considered and used to contrast the potential effects of age. Results suggest that modulation frequency and extent (amplitude), as well as the amount of vocal fold overall strain, all affect the change in stress relaxation with modulation added. Generally, the vocal fold cover reduces the rate of relaxation while the opposite is true for the vocal ligament. Further, higher modulation frequencies appear to reduce the rate of relaxation, primarily affecting the ligament. The potential benefits of cyclic strain, often found in vibrato (around 5 Hz modulation) and intonational inflection, are discussed in terms of vocal effort and vocal pitch maintenance. Additionally, elderly tissue appears to not exhibit these benefits to modulation. The exacerbating effect such modulations may have on certain voice disorders, such as muscle tension dysphonia, are explored

Identifying susceptibility genes by using joint tests of association and linkage and accounting for epistasis

Simulated Genetic Analysis Workshop14 data were analyzed by jointly testing linkage and association and by accounting for epistasis using a candidate gene approach. Our group was unblinded to the "answers." The 48 single-nucleotide polymorphisms (SNPs) within the six disease loci were analyzed in addition to five SNPs from each of two non-disease-related loci. Affected sib-parent data was extracted from the first 10 replicates for populations Aipotu, Kaarangar, and Danacaa, and analyzed separately for each replicate. We developed a likelihood for testing association and/or linkage using data from affected sib pairs and their parents. Identical-by-descent (IBD) allele sharing between sibs was explicitly modeled using a conditional logistic regression approach and incorporating a covariate that represents expected IBD allele sharing given the genotypes of the sibs and their parents. Interactions were accounted for by performing likelihood ratio tests in stages determined by the highest order interaction term in the model. In the first stage, main effects were tested independently, and in subsequent stages, multilocus effects were tested conditional on significant marginal effects. A reduction in the number of tests performed was achieved by prescreening gene combinations with a goodness-of-fit chi square statistic that depended on mating-type frequencies. SNP-specific joint effects of linkage and association were identified for loci D1, D2, D3, and D4 in multiple replicates. The strongest effect was for SNP B03T3056, which had a median p-value of 1.98 × 10(-34). No two- or three-locus effects were found in more than one replicate

Modeling measurement error in tumor characterization studies

<p>Abstract</p> <p>Background</p> <p>Etiologic studies of cancer increasingly use molecular features such as gene expression, DNA methylation and sequence mutation to subclassify the cancer type. In large population-based studies, the tumor tissues available for study are archival specimens that provide variable amounts of amplifiable DNA for molecular analysis. As molecular features measured from small amounts of tumor DNA are inherently noisy, we propose a novel approach to improve statistical efficiency when comparing groups of samples. We illustrate the phenomenon using the MethyLight technology, applying our proposed analysis to compare <it>MLH1 </it>DNA methylation levels in males and females studied in the Colon Cancer Family Registry.</p> <p>Results</p> <p>We introduce two methods for computing empirical weights to model heteroscedasticity that is caused by sampling variable quantities of DNA for molecular analysis. In a simulation study, we show that using these weights in a linear regression model is more powerful for identifying differentially methylated loci than standard regression analysis. The increase in power depends on the underlying relationship between variation in outcome measure and input DNA quantity in the study samples.</p> <p>Conclusions</p> <p>Tumor characteristics measured from small amounts of tumor DNA are inherently noisy. We propose a statistical analysis that accounts for the measurement error due to sampling variation of the molecular feature and show how it can improve the power to detect differential characteristics between patient groups.</p

Alice: The Rosetta Ultraviolet Imaging Spectrograph

We describe the design, performance and scientific objectives of the NASA-funded ALICE instrument aboard the ESA Rosetta asteroid flyby/comet rendezvous mission. ALICE is a lightweight, low-power, and low-cost imaging spectrograph optimized for cometary far-ultraviolet (FUV) spectroscopy. It will be the first UV spectrograph to study a comet at close range. It is designed to obtain spatially-resolved spectra of Rosetta mission targets in the 700-2050 A spectral band with a spectral resolution between 8 A and 12 A for extended sources that fill its ~0.05 deg x 6.0 deg field-of-view. ALICE employs an off-axis telescope feeding a 0.15-m normal incidence Rowland circle spectrograph with a concave holographic reflection grating. The imaging microchannel plate detector utilizes dual solar-blind opaque photocathodes (KBr and CsI) and employs a 2 D delay-line readout array. The instrument is controlled by an internal microprocessor. During the prime Rosetta mission, ALICE will characterize comet 67P/Churyumov-Gerasimenko's coma, its nucleus, and the nucleus/coma coupling; during cruise to the comet, ALICE will make observations of the mission's two asteroid flyby targets and of Mars, its moons, and of Earth's moon. ALICE has already successfully completed the in-flight commissioning phase and is operating normally in flight. It has been characterized in flight with stellar flux calibrations, observations of the Moon during the first Earth fly-by, and observations of comet Linear T7 in 2004 and comet 9P/Tempel 1 during the 2005 Deep Impact comet-collision observing campaignComment: 11 pages, 7 figure