Modelling time course gene expression data with finite mixtures of linear additive models

Summary: A model class of finite mixtures of linear additive models is presented. The component-specific parameters in the regression models are estimated using regularized likelihood methods. The advantages of the regularization are that (i) the pre-specified maximum degrees of freedom for the splines is less crucial than for unregularized estimation and that (ii) for each component individually a suitable degree of freedom is selected in an automatic way. The performance is evaluated in a simulation study with artificial data as well as on a yeast cell cycle dataset of gene expression levels over time

Multiaxial fatigue assessment of crankshafts by local stress and critical plane approach

For multiaxially-loaded parts several stress-based fatigue assessment concepts are applicable mostly taking uniaxial test results as basis. These approaches work well in case of proportional loading states, but on contrary, for non-proportional stress conditions, implying a change of the principal stress direction, deviations in the fatigue life estimation may occur. The aim of this study is to evaluate the cyclic multiaxial material behavior experimentally and to proof the applicability of stress-based methods to assess the fatigue strength. The investigated base materials incorporate the commonly applied crankshaft steels 50CrMo4 and 34CrNiMo6 without surface-layer post-treatments. Extensive fatigue tests with small-scale specimens are performed to evaluate the material behavior under cyclic loading. The experiments include basic uniaxial characterizations, such as notch stress sensitivity and effect of loading type, including tests under tension, rotating bending, and torsion loading. Additionally, combined loading tests with proportional and non-proportional situations are presented to reveal the fatigue resistance for multiaxial stress states. Significant loading conditions, such as proportional stress under rotating bending and torsion, and further on, non-proportional effects like phase shifts and varying frequency ratios are presented. The local fatigue strength assessment is performed on the basis of the critical plane approach, whereat the normal and shear stresses are transformed in numerous cutting planes. Equivalent stress hypotheses are applied and compared with the experiments showing that the Huber-Mises-Hencky criterion fits well to the test results in case of proportional rotating bending and torsion loading

The COBE Diffuse Infrared Background Experiment Search for the Cosmic Infrared Background: IV. Cosmological Implications

In this paper we examine the cosmological constraints of the recent DIRBE and FIRAS detection of the extragalactic background light between 125-5000 microns on the metal and star formation histories of the universe.Comment: 38 pages and 9 figures. Accepted for publications in The Astrophysical Journa

Gr1+IL-4-producing innate cells are induced in response to Th2 stimuli and suppress Th1-dependent antibody responses

Alum is used as a vaccine adjuvant and induces T<sub>h</sub>2 responses and T<sub>h</sub>2-driven antibody isotype production against co-injected antigens. Alum also promotes the appearance in the spleen of Gr1+IL-4+ innate cells that, via IL-4 production, induce MHC II-mediated signaling in B cells. To investigate whether these Gr1+ cells accumulate in the spleen in response to other T<sub>h</sub>2-inducing stimuli and to understand some of their functions, the effects of injection of alum and eggs from the helminth, Schistosoma mansoni, were compared. Like alum, schistosome eggs induced the appearance of Gr1+IL-4+ cells in spleen and promoted MHC II-mediated signaling in B cells. Unlike alum, however, schistosome eggs did not promote CD4 T cell responses against co-injected antigens, suggesting that the effects of alum or schistosome eggs on splenic B cells cannot by themselves explain the T cell adjuvant properties of alum. Accordingly, depletion of IL-4 or Gr1+ cells in alum-injected mice had no effect on the ability of alum to improve expansion of primary CD4 T cells. However, Gr1+ cells and IL-4 played some role in the effects of alum, since depletion of either resulted in antibody responses to antigen that included not only the normal T<sub>h</sub>2-driven isotypes, like IgG1, but also a T<sub>h</sub>1-driven isotype, IgG2c. These data suggest that alum affects the immune response in at least two ways: one, independent of Gr1+ cells and IL-4, that promotes CD4 T cell proliferation and another, via Gr1+IL-4+ cells, that participates in the polarization of the response

Combined transcriptomic-(1)H NMR metabonomic study reveals yhat monoethylhexyl phthalate stimulates adipogenesis and glyceroneogenesis in human adipocytes

Adipose tissue is a major storage site for lipophilic environmental contaminants. The environmental metabolic disruptor hypothesis postulates that some pollutants can promote obesity or metabolic disorders by activating nuclear receptors involved in the control of energetic homeostasis. In this context, monoethylhexyl phthalate (MEHP) is of particular concern since it was shown to activate the peroxisome proliferator-activated receptor γ (PPARγ) in 3T3-L1 murine preadipocytes. In the present work, we used an untargeted, combined transcriptomic-(1)H NMR-based metabonomic approach to describe the overall effect of MEHP on primary cultures of human subcutaneous adipocytes differentiated in vitro. MEHP stimulated rapidly and selectively the expression of genes involved in glyceroneogenesis, enhanced the expression of the cytosolic phosphoenolpyruvate carboxykinase, and reduced fatty acid release. These results demonstrate that MEHP increased glyceroneogenesis and fatty acid reesterification in human adipocytes. A longer treatment with MEHP induced the expression of genes involved in triglycerides uptake, synthesis, and storage; decreased intracellular lactate, glutamine, and other amino acids; increased aspartate and NAD, and resulted in a global increase in triglycerides. Altogether, these results indicate that MEHP promoted the differentiation of human preadipocytes to adipocytes. These mechanisms might contribute to the suspected obesogenic effect of MEHP

Counter-propagating radiative shock experiments on the Orion laser and the formation of radiative precursors

We present results from new experiments to study the dynamics of radiative shocks, reverse shocks and radiative precursors. Laser ablation of a solid piston by the Orion high-power laser at AWE Aldermaston UK was used to drive radiative shocks into a gas cell initially pressurised between $0.1$ and $1.0 \ bar with different noble gases. Shocks propagated at {80 \pm 10 \ km/s} and experienced strong radiative cooling resulting in post-shock compressions of { \times 25 \pm 2}. A combination of X-ray backlighting, optical self-emission streak imaging and interferometry (multi-frame and streak imaging) were used to simultaneously study both the shock front and the radiative precursor. These experiments present a new configuration to produce counter-propagating radiative shocks, allowing for the study of reverse shocks and providing a unique platform for numerical validation. In addition, the radiative shocks were able to expand freely into a large gas volume without being confined by the walls of the gas cell. This allows for 3-D effects of the shocks to be studied which, in principle, could lead to a more direct comparison to astrophysical phenomena. By maintaining a constant mass density between different gas fills the shocks evolved with similar hydrodynamics but the radiative precursor was found to extend significantly further in higher atomic number gases (\sim$$4$ times further in xenon than neon). Finally, 1-D and 2-D radiative-hydrodynamic simulations are presented showing good agreement with the experimental data.Comment: HEDLA 2016 conference proceeding

Weak pairwise correlations imply strongly correlated network states in a neural population

Biological networks have so many possible states that exhaustive sampling is impossible. Successful analysis thus depends on simplifying hypotheses, but experiments on many systems hint that complicated, higher order interactions among large groups of elements play an important role. In the vertebrate retina, we show that weak correlations between pairs of neurons coexist with strongly collective behavior in the responses of ten or more neurons. Surprisingly, we find that this collective behavior is described quantitatively by models that capture the observed pairwise correlations but assume no higher order interactions. These maximum entropy models are equivalent to Ising models, and predict that larger networks are completely dominated by correlation effects. This suggests that the neural code has associative or error-correcting properties, and we provide preliminary evidence for such behavior. As a first test for the generality of these ideas, we show that similar results are obtained from networks of cultured cortical neurons.Comment: Full account of work presented at the conference on Computational and Systems Neuroscience (COSYNE), 17-20 March 2005, in Salt Lake City, Utah (http://cosyne.org

Well posedness of an isothermal diffusive model for binary mixtures of incompressible fluids

We consider a model describing the behavior of a mixture of two incompressible fluids with the same density in isothermal conditions. The model consists of three balance equations: continuity equation, Navier-Stokes equation for the mean velocity of the mixture, and diffusion equation (Cahn-Hilliard equation). We assume that the chemical potential depends upon the velocity of the mixture in such a way that an increase of the velocity improves the miscibility of the mixture. We examine the thermodynamic consistence of the model which leads to the introduction of an additional constitutive force in the motion equation. Then, we prove existence and uniqueness of the solution of the resulting differential problem

Free induction signal from biexcitons and bound excitons

A theory of the free induction signal from biexcitons and bound excitons is presented. The simultaneous existence of the exciton continuum and a bound state is shown to result in a new type of time dependence of the free induction. The optically detected signal increases in time and oscillates with increasing amplitude until damped by radiative or dephasing processes. Radiative decay is anomalously fast and can result in strong picosecond pulses. The expanding area of a coherent exciton polarization (inflating antenna), produced by the exciting pulse, is the underlying physical mechanism. The developed formalism can be applied to different biexciton transients.Comment: RevTeX, 20 p. + 2 ps fig. To appear in Phys. Rev. B1

Mapping of bioavailable strontium isotope ratios in France for archaeological provenance studies

© 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 24 month embargo from date of publication (Dec 2017) in accordance with the publisher’s archiving policyStrontium isotope ratios (87Sr/86Sr) of archaeological samples (teeth and bones) can be used to track mobility and migration across geologically distinct landscapes. However, traditional interpolation algorithms and classification approaches used to generate Sr isoscapes are often limited in predicting multiscale 87Sr/86Sr patterning. Here we investigate the suitability of plant samples and soil leachates from the IRHUM database (www.irhumdatabase.com) to create a bioavailable 87Sr/86Sr map using a novel geostatistical framework. First, we generated an 87Sr/86Sr map by classifying 87Sr/86Sr values into five geologically-representative isotope groups using cluster analysis. The isotope groups were then used as a covariate in kriging to integrate prior geological knowledge of Sr cycling with the information contained in the bioavailable dataset and enhance 87Sr/86Sr predictions. Our approach couples the strengths of classification and geostatistical methods to generate more accurate 87Sr/86Sr predictions (Root Mean Squared Error = 0.0029) with an estimate of spatial uncertainty based on lithology and sample density. This bioavailable Sr isoscape is applicable for provenance studies in France, and the method is transferable to other areas with high sampling density. While our method is a step forward in generating accurate 87Sr/86Sr isoscapes, the remaining uncertainty also demonstrates that fine-modelling of 87Sr/86Sr variability is challenging and requires more than geological maps for accurately predicting 87Sr/86Sr variations across the landscape. Future efforts should focus on increasing sampling density and developing predictive models to further quantify and predict the processes that lead to 87Sr/86Sr variability