Multiscale Bone Remodelling with Spatial P Systems

Many biological phenomena are inherently multiscale, i.e. they are characterized by interactions involving different spatial and temporal scales simultaneously. Though several approaches have been proposed to provide "multilayer" models, only Complex Automata, derived from Cellular Automata, naturally embed spatial information and realize multiscaling with well-established inter-scale integration schemas. Spatial P systems, a variant of P systems in which a more geometric concept of space has been added, have several characteristics in common with Cellular Automata. We propose such a formalism as a basis to rephrase the Complex Automata multiscaling approach and, in this perspective, provide a 2-scale Spatial P system describing bone remodelling. The proposed model not only results to be highly faithful and expressive in a multiscale scenario, but also highlights the need of a deep and formal expressiveness study involving Complex Automata, Spatial P systems and other promising multiscale approaches, such as our shape-based one already resulted to be highly faithful.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005

Epigenomics of being bullied: changes in DNA methylation following bullying exposure

Bullying among children is ubiquitous and associated with pervasive mental health problems. However, little is known about the biological pathways that change after exposure to bullying. Epigenome-wide changes in DNA methylation in peripheral blood were studied from pre- to post measurement of bullying exposure, in a longitudinal study of the population-based Generation R Study and Avon Longitudinal Study of Parents and Children (combined n = 1,352). Linear mixed-model results were meta-analysed to estimate how DNA methylation changed as a function of exposure to bullying. Sensitivity analyses including co-occurring child characteristics and risks were performed, as well as a Gene Ontology analysis. A candidate follow-up was employed for CpG (cytosine-phosphate-guanine) sites annotated to 5-HTT and NR3C1. One site, cg17312179, showed small changes in DNA methylation associated to bullying exposure (b = −2.67e-03, SE = 4.97e-04, p = 7.17e-08). This site is annotated to RAB14, an oncogene related to Golgi apparatus functioning, and its methylation levels decreased for exposed but increased for non-exposed. This result was consistent across sensitivity analyses. Enriched Gene Ontology pathways for differentially methylated sites included cardiac function and neurodevelopmental processes. Top CpG sites tended to have overall low levels of DNA methylation, decreasing in exposed, increasing in non-exposed individuals. There were no gene-wide corrected findings for 5-HTT and NR3C1. This is the first study to identify changes in DNA methylation associated with bullying exposure at the epigenome-wide significance level. Consistent with other population-based studies, we do not find evidence for strong associations between bullying exposure and DNA methylation

The solution of nonlinear boundary-value transport problems in electron and plasma devices

A method of solution of the nonlinear Landau-Vlasov equation which occurs in charged particle transport phenomena is described. The method is similar in concept to the Spherical Harmonics Method of neutron transport theory, since the particle distribution function is expanded in orthogonal functions of velocity to obtain an infinite set of partial differential equations. The nonlinearity arises when the particle interactions are taken into account in the force term of the Landau-Vlasov equation. The latter is introduced into the equation iteratively and a numerical integration routine is described to integrate the set of equations resulting from a finite (nth order) truncation of the expansion. The truncated equations, which are for the first n velocity moments of the distribution function, are such that these moments satisfy the untruncated equations also, whereas higher moment equations are modified by a fictitious source term. The convergence of the finite-difference equations and the convergence of the finite-difference solution to the solution of the differential equations is proved for the linear case in which the force is assumed to be known. Computational evidence of the convergence in the nonlinear case is provided, although no mathematical proof has so far been developed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33476/1/0000881.pd

Epigenome-wide change and variation in DNA methylation in childhood: trajectories from birth to late adolescence

DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5019 blood samples collected at multiple time-points from birth to late adolescence from 2348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases, DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for non-linear change and inter-individual variation in non-linear trajectories was somewhat less common (11 and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. In contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often non-linear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu. ac.uk.Molecular Epidemiolog

Nonthermal phenomena in clusters of galaxies

Recent observations of high energy (> 20 keV) X-ray emission in a few clusters of galaxies broaden our knowledge of physical phenomena in the intracluster space. This emission is likely to be nonthermal, probably resulting from Compton scattering of relativistic electrons by the cosmic microwave background (CMB) radiation. Direct evidence for the presence of relativistic electrons in some 50 clusters comes from measurements of extended radio emission in their central regions. We briefly review the main results from observations of extended regions of radio emission, and Faraday rotation measurements of background and cluster radio sources. The main focus of the review are searches for nonthermal X-ray emission conducted with past and currently operating satellites, which yielded appreciable evidence for nonthermal emission components in the spectra of a few clusters. This evidence is clearly not unequivocal, due to substantial observational and systematic uncertainties, in addition to virtually complete lack of spatial information. If indeed the emission has its origin in Compton scattering of relativistic electrons by the CMB, then the mean magnetic field strength and density of relativistic electrons in the cluster can be directly determined. Knowledge of these basic nonthermal quantities is valuable for the detailed description of processes in intracluster gas and for the origin of magnetic fields.Comment: 23 pages, 7 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 5; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Outcome Measures of New Technologies in Uveal Melanoma Review from the European Vision Institute Special Interest Focus Group Meeting

Uveal melanoma UM is the most common primary intraocular tumor in adults. New diagnostic procedures and basic science discoveries continue to change our patient management paradigms. A recent meeting of the European Vision Institute EVI special interest focus group was held on Outcome Measures of New Technologies in Uveal Melanoma, addressing the latest advances in UM, starting with genetic developments, then moving on to imaging and treatment of the primary tumor, as well as to investigating the most recent developments in treating metastases, and eventually taking care of the patient s well being. This review highlights the meeting s presentations in the context of the published literatur

Maternal depression during pregnancy and cord blood DNA methylation: findings from the Avon Longitudinal Study of Parents and Children

Up to 13% of women may experience symptoms of depression during pregnancy or in the postpartum period. Depression during pregnancy has been associated with an increased risk of adverse neurodevelopmental outcomes in the child and epigenetic mechanisms could be one of the biological pathways to explain this association. In 844 mother–child pairs from the Avon Longitudinal Study of Parents and Children, we carried out an epigenome-wide association study (EWAS) to investigate associations between prospectively collected data on maternal depression ascertained by the Edinburgh Postnatal Depression Scale in pregnancy and DNA methylation in the cord blood of newborn offspring. In individual site analysis, we identified two CpG sites associated with maternal depression in the middle part of pregnancy. In our regional analysis, we identified 39 differentially methylated regions (DMRs). Seven DMRs were associated with depression at any time point during pregnancy, 7 associated with depression in mid-pregnancy, 23 were associated with depression in late pregnancy, and 2 DMRs were associated with depression throughout pregnancy. Several of these map to genes associated with psychiatric disease and brain development. We attempted replication in The Generation R Study and could not replicate our results. Although our findings in ALSPAC suggest that maternal depression could be associated with cord blood DNA methylation the results should be viewed as preliminary and hypothesis generating until further replicated in a larger sample

Sediment routing and basin evolution in Proterozoic to Mesozoic east Gondwana: A case study from southern Australia

Sedimentary rocks along the southern margin of Australia host an important record of the break-up history of east Gondwana, as well as fragments of a deeper geological history, which collectively help inform the geological evolution of a vast and largely underexplored region. New drilling through Cenozoic cover has allowed examination of the Cretaceous rift-related Madura Shelf sequence (Bight Basin), and identification of two new stratigraphic units beneath the shelf; the possibly Proterozoic Shanes Dam Conglomerate and the interpreted Palaeozoic southern Officer Basin unit, the Decoration Sandstone. Recognition of these new units indicates an earlier basinal history than previously known. Lithostratigraphy of the new drillcore has been integrated with that published from onshore and offshore cores to present isopach maps of sedimentary cover on the Madura Shelf. New palynological data demonstrate progression from more localised freshwater-brackish fluvio-lacustrine clastics in the early Cretaceous (Foraminisporis wonthaggiensis – Valanginian to Barremian) to widespread topography-blanketing, fully marine, glauconitic mudrocks in the mid Cretaceous (Endoceratium ludbrookiae – Albian). Geochronology and Hf-isotope geochemistry show detrital zircon populations from the Madura Shelf are comparable to those from the southern Officer Basin, as well as Cenozoic shoreline and palaeovalley sediments in the region. The detrital zircon population from the Shanes Dam Conglomerate is defined by a unimodal ~1400 Ma peak, which correlates with directly underlying crystalline basement of the Madura Province. Peak ages of ~1150 Ma and ~1650 Ma dominate the age spectra of all other samples, indicating a stable sediment reservoir through much of the Phanerozoic, with sediments largely sourced from the Albany-Fraser Orogen and Musgrave Province (directly and via multiple recycling events). The Madura Shelf detrital zircon population differs from published data for the Upper CretaceousCeduna Delta to the east, indicating significant differences in sediment provenance and routing between the Ceduna Sub-basin and central Bight Basin