Radar based improvements and diagnosis of the convective capabilities of the cosmo-2 model

In the last few years the resolution of numerical weather prediction (nwp) became higher and higher with the progresses of technology and knowledge. As a consequence, a great number of initial data became fundamental for a correct initialization of the models. The potential of radar observations has long been recognized for improving the initial conditions of high-resolution nwp models, while operational application becomes more frequent. The fact that many nwp centres have recently taken into operations convection-permitting forecast models, many of which assimilate radar data, emphasizes the need for an approach to providing quality information which is needed in order to avoid that radar errors degrade the model's initial conditions and, therefore, its forecasts. Environmental risks can can be related with various causes: meteorological, seismical, hydrological/hydraulic. Flash floods have horizontal dimension of 1-20 Km and can be inserted in mesoscale gamma subscale, this scale can be modeled only with nwp model with the highest resolution as the COSMO-2 model. One of the problems of modeling extreme convective events is related with the atmospheric initial conditions, in fact the scale dimension for the assimilation of atmospheric condition in an high resolution model is about 10 Km, a value too high for a correct representation of convection initial conditions. Assimilation of radar data with his resolution of about of Km every 5 or 10 minutes can be a solution for this problem. In this contribution a pragmatic and empirical approach to deriving a radar data quality description is proposed to be used in radar data assimilation and more specifically for the latent heat nudging (lhn) scheme. Later the the nvective capabilities of the cosmo-2 model are investigated through some case studies. Finally, this work shows some preliminary experiments of coupling of a high resolution meteorological model with an Hydrological one.

Pulsatile shear and Gja5 modulate arterial identity and remodeling events during flow-driven arteriogenesis

In the developing chicken embryo yolk sac vasculature, the expression of arterial identity genes requires arterial hemodynamic conditions. We hypothesize that arterial flow must provide a unique signal that is relevant for supporting arterial identity gene expression and is absent in veins. We analyzed factors related to flow, pressure and oxygenation in the chicken embryo vitelline vasculature in vivo. The best discrimination between arteries and veins was obtained by calculating the maximal pulsatile increase in shear rate relative to the time-averaged shear rate in the same vessel: the relative pulse slope index (RPSI). RPSI was significantly higher in arteries than veins. Arterial endothelial cells exposed to pulsatile shear in vitro augmented arterial marker expression as compared with exposure to constant shear. The expression of Gja5 correlated with arterial flow patterns: the redistribution of arterial flow provoked by vitelline artery ligation resulted in flow-driven collateral arterial network formation and was associated with increased expression of Gja5. In situ hybridization in normal and ligation embryos confirmed that Gja5 expression is confined to arteries and regulated by flow. In mice, Gja5 (connexin 40) was also expressed in arteries. In the adult, increased flow drives arteriogenesis and the formation of collateral arterial networks in peripheral occlusive diseases. Genetic ablation of Gja5 function in mice resulted in reduced arteriogenesis in two occlusion models. We conclude that pulsatile shear patterns may be central for supporting arterial identity, and that arterial Gja5 expression plays a functional role in flow-driven arteriogenesis.

Domains of physical activity and all-cause mortality: systematic review and dose-response meta-analysis of cohort studies

Background The dose–response relation between physical activity and all-cause mortality is not well defined at present. We conducted a systematic review and meta-analysis to determine the association with all-cause mortality of different domains of physical activity and of defined increases in physical activity and energy expenditure. Methods MEDLINE, Embase and the Cochrane Library were searched up to September 2010 for cohort studies examining all-cause mortality across different domains and levels of physical activity in adult general populations. We estimated combined risk ratios (RRs) associated with defined increments and recommended levels, using random-effects meta-analysis and dose–response meta-regression models. Results Data from 80 studies with 1 338 143 participants (118 121 deaths) were included. Combined RRs comparing highest with lowest activity levels were 0.65 [95% confidence interval (95% CI) 0.60–0.71] for total activity, 0.74 (95% CI 0.70–0.77) for leisure activity, 0.64 (95% CI 0.55–0.75) for activities of daily living and 0.83 (95% CI 0.71–0.97) for occupational activity. RRs per 1-h increment per week were 0.91 (95% CI 0.87–0.94) for vigorous exercise and 0.96 (95% CI 0.93–0.98) for moderate-intensity activities of daily living. RRs corresponding to 150 and 300 min/week of moderate to vigorous activity were 0.86 (95% CI 0.80–0.92) and 0.74 (95% CI 0.65–0.85), respectively. Mortality reductions were more pronounced in women. Conclusion Higher levels of total and domain-specific physical activity were associated with reduced all-cause mortality. Risk reduction per unit of time increase was largest for vigorous exercise. Moderate-intensity activities of daily living were to a lesser extent beneficial in reducing mortality.

Relationship of porcine IGF2 imprinting status to DNA methylation at the H19 DMD and the IGF2 DMRs 1 and 2

BACKGROUND: Porcine IGF2 and the H19 genes are imprinted. The IGF2 is paternally expressed, while the H19 gene is maternally expressed. Extensive studies in mice established a boundary model indicating that the H19 differentially methylated domain (DMD) controls, upon binding with the CTCF protein, reciprocal imprinting of the IGF2 and the H19 genes. IGF2 transcription is tissue and development specific involving the use of 4 promoters. In the liver of adult Large White boars IGF2 is expressed from both parental alleles, whereas in skeletal muscle and kidney tissues we observed variable relaxation of IGF2 imprinting. We hypothesized that IGF2 expression from both paternal alleles and relaxation of IGF2 imprinting is reflected in differences in DNA methylation patterns at the H19 DMD and IGF2 differentially methylated regions 1 and 2 (DMR1 and DMR2). RESULTS: Bisulfite sequencing analysis did not show any differences in DNA methylation at the three porcine CTCF binding sites in the H19 DMD between liver, muscle and kidney tissues of adult pigs. A DNA methylation analysis using methyl-sensitive restriction endonuclease SacII and 'hot-stop' PCR gave consistent results with those from the bisulfite sequencing analysis. We found that porcine H19 DMD is distinctly differentially methylated, at least for the region formally confirmed by two SNPs, in liver, skeletal muscle and kidney of foetal, newborn and adult pigs, independent of the combined imprinting status of all IGF2 expressed transcripts. DNA methylation at CpG sites in DMR1 of foetal liver was significantly lower than in the adult liver due to the presence of hypomethylated molecules. An allele specific analysis was performed for IGF2 DMR2 using a SNP in the IGF2 3'-UTR. The maternal IGF2 DMR2 of foetal and newborn liver revealed a higher DNA methylation content compared to the respective paternal allele. CONCLUSIONS: Our results indicate that the IGF2 imprinting status is transcript-specific. Biallelic IGF2 expression in adult porcine liver and relaxation of IGF2 imprinting in porcine muscle were a common feature. These results were consistent with the IGF2 promoter P1 usage in adult liver and IGF2 promoter P2, P3 and P4 usages in muscle. The results showed further that bialellic IGF2 expression in liver and relaxation of imprinting in muscle and kidney were not associated with DNA methylation variation at and around at least one CTCF binding site in H19 DMD. The imprinting status in adult liver, muscle and kidney tissues were also not reflected in the methylation patterns of IGF2 DMRs 1 and 2.

Model Checking for ROC Regression Analysis

The Receiver Operating Characteristic (ROC) curve is a prominent tool for characterizing the accuracy of continuous diagnostic test. To account for factors that might invluence the test accuracy, various ROC regression methods have been proposed. However, as in any regression analysis, when the assumed models do not fit the data well, these methods may render invalid and misleading results. To date practical model checking techniques suitable for validating existing ROC regression models are not yet available. In this paper, we develop cumulative residual based procedures to graphically and numerically assess the goodness-of-fit for some commonly used ROC regression models, and show how specific components of these models can be examined within this framework. We derive asymptotic null distributions for the residual process and discuss resampling procedures to approximate these distributions in practice. We illustrate our methods with a dataset from the Cystic Fibrosis registry.

RANDOM EFFECTS MODELS IN A META-ANALYSIS OF THE ACCURACY OF DIAGNOSTIC TESTS WITHIN A GOLD STANDARD IN THE PRESENCE OF MISSING DATA

In evaluating the accuracy of diagnosis tests, it is common to apply two imperfect tests jointly or sequentially to a study population. In a recent meta-analysis of the accuracy of microsatellite instability testing (MSI) and traditional mutation analysis (MUT) in predicting germline mutations of the mismatch repair (MMR) genes, a Bayesian approach (Chen, Watson, and Parmigiani 2005) was proposed to handle missing data resulting from partial testing and the lack of a gold standard. In this paper, we demonstrate an improved estimation of the sensitivities and specificities of MSI and MUT by using a nonlinear mixed model and a Bayesian hierarchical model, both of which account for the heterogeneity across studies through study-specific random effects. The methods can be used to estimate the accuracy of two imperfect diagnostic tests in other meta-analyses when the prevalence of disease, the sensitivities and/or the specificities of diagnostic tests are heterogeneous among studies. Furthermore, simulation studies have demonstrated the importance of carefully selecting appropriate random effects on the estimation of diagnostic accuracy measurements in this scenario.

EFFECT OF ELECTRICAL DISCHARGE PATTERN ON SPARK IGNITED FLAME KERNEL DEVELOPMENT

Fuel-lean combustion and exhaust gas recirculation (EGR) in spark ignition engines improve engine efficiency and reduce emission. However, flame initiation becomes more difficult in lean and dilute fuel-air mixture with traditional spark discharge. This research proposal will first provide an intensive review on topics related to spark ignition including properties of electrical discharge, flame kernel behavior and spark ignition modeling and simulation. Focus will be laid on electrical discharge pattern effect as it is showing prospect in extending ignition limits in SI engines. An experimental setup has been built with an optically accessible constant volume combustion vessel. Multiple imaging techniques as well as spectroscopy will be applied. By varying spark discharge patterns, preliminary test results are available on consequent flame kernel development. In addition to experimental investigation of spark plasma and flame kernel development, spark ignition modeling with detailed description of plasma channel is also proposed for this study.

Extracting models from IDEs

Systems must co-evolve with their context. Reverse engineering tools are a great help in this process of required adaption. In order for these tools to be flexible, they work with models, abstract representations of the source code. The extraction of such information from source code can be done using a parser. However, it is fairly tedious to build new parsers. And this is made worse by the fact that it has to be done over and over again for every language we want to analyze. In this paper we propose a novel approach which minimizes the knowledge required of a certain language for the extraction of models implemented in that language by reflecting on the implementation of preparsed ASTs provided by an IDE. In a second phase we use a technique referred to as Model Mapping by Example to map platform dependent models onto domain specific model.

Kostenorientiertes Controlling von E-Learning-Plattformen mit dem TCO-Konzept

Zur administrativen Unterstützung von Lehr- und Lernprozessen werden E-Learning-Plattformen eingesetzt, die auf der Grundlage des Internet Funktionen zur Distribution von Lehr- und Lernmaterialien und zur Kommunikation zwischen Lehrenden und Lernenden anbieten. Zahlreiche wissenschaftliche Beiträge und Marktstudien beschäftigen sich mit der multikriteriellen Evaluation dieser Softwareprodukte zur informatorischen Fundierung strategischer Investitionsentscheidungen. Demgegenüber werden Instrumente zum kostenorientierten Controlling von E-Learning-Plattformen allenfalls marginal thematisiert. Dieser Beitrag greift daher das Konzept der Total Cost of Ownership (TCO) auf, das einen methodischen Ansatzpunkt zur Schaffung von Kostentransparenz von E-Learning-Plattformen bildet. Aufbauend auf den konzeptionellen Grundlagen werden Problembereiche und Anwendungspotenziale für das kostenorientierte Controlling von LMS identifiziert. Zur softwaregestützten Konstruktion und Analyse von TCO-Modellen wird das Open Source-Werkzeug TCO-Tool eingeführt und seine Anwendung anhand eines synthetischen Fallbeispiels erörtert. Abschließend erfolgt die Identifikation weiterführender Entwicklungsperspektiven des TCO-Konzepts im Kontext des E-Learning. Die dargestellte Thematik ist nicht nur von theoretischem Interesse, sondern adressiert auch den steigenden Bedarf von Akteuren aus der Bildungspraxis nach Instrumenten zur informatorischen Fundierung von Investitions- und Desinvestitionsentscheidungen im Umfeld des E-Learning.

An anisotropic elastic-viscoplastic damage model for bone tissue

A new anisotropic elastic-viscoplastic damage constitutive model for bone is proposed using an eccentric elliptical yield criterion and nonlinear isotropic hardening. A micromechanics-based multiscale homogenization scheme proposed by Reisinger et al. is used to obtain the effective elastic properties of lamellar bone. The dissipative process in bone is modeled as viscoplastic deformation coupled to damage. The model is based on an orthotropic ecuntric elliptical criterion in stress space. In order to simplify material identification, an eccentric elliptical isotropic yield surface was defined in strain space, which is transformed to a stress-based criterion by means of the damaged compliance tensor. Viscoplasticity is implemented by means of the continuous Perzyna formulation. Damage is modeled by a scalar function of the accumulated plastic strain D(κ) , reducing all element s of the stiffness matrix. A polynomial flow rule is proposed in order to capture the rate-dependent post-yield behavior of lamellar bone. A numerical algorithm to perform the back projection on the rate-dependent yield surface has been developed and implemented in the commercial finite element solver Abaqus/Standard as a user subroutine UMAT. A consistent tangent operator has been derived and implemented in order to ensure quadratic convergence. Correct implementation of the algorithm, convergence, and accuracy of the tangent operator was tested by means of strain- and stress-based single element tests. A finite element simulation of nano- indentation in lamellar bone was finally performed in order to show the abilities of the newly developed constitutive model.

Is low self-esteem a risk factor for depression? Findings from a longitudinal study of Mexican-origin youth

We examined the relation between low self-esteem and depression using longitudinal data from a sample of 674 Mexican-origin early adolescents who were assessed at age 10 and 12 years. Results supported the vulnerability model, which states that low self-esteem is a prospective risk factor for depression. Moreover, results suggested that the vulnerability effect of low self-esteem is driven, for the most part, by general evaluations of worth (i.e., global self-esteem), rather than by domain-specific evaluations of academic competence, physical appearance, and competence in peer relationships. The only domain-specific self-evaluation that showed a prospective effect on depression was honesty-trustworthiness. The vulnerability effect of low self-esteem held for male and female adolescents, for adolescents born in the United States versus Mexico, and across different levels of pubertal status. Finally, the vulnerability effect held when we controlled for several theoretically relevant 3rd variables (i.e., social support, maternal depression, stressful events, and relational victimization) and for interactive effects between self-esteem and the 3rd variables. The present study contributes to an emerging understanding of the link between self-esteem and depression and provides much needed data on the antecedents of depression in ethnic minority populations

Experimental Validation of Finite Element Analysis of Human Vertebral Collapse Under Large Compressive Strains

Osteoporosis-related vertebral fractures represent a major health problem in elderly populations. Such fractures can often only be diagnosed after a substantial deformation history of the vertebral body. Therefore, it remains a challenge for clinicians to distinguish between stable and progressive potentially harmful fractures. Accordingly, novel criteria for selection of the appropriate conservative or surgical treatment are urgently needed. Computer tomography-based finite element analysis is an increasingly accepted method to predict the quasi-static vertebral strength and to follow up this small strain property longitudinally in time. A recent development in constitutive modeling allows us to simulate strain localization and densification in trabecular bone under large compressive strains without mesh dependence. The aim of this work was to validate this recently developed constitutive model of trabecular bone for the prediction of strain localization and densification in the human vertebral body subjected to large compressive deformation. A custom-made stepwise loading device mounted in a high resolution peripheral computer tomography system was used to describe the progressive collapse of 13 human vertebrae under axial compression. Continuum finite element analyses of the 13 compression tests were realized and the zones of high volumetric strain were compared with the experiments. A fair qualitative correspondence of the strain localization zone between the experiment and finite element analysis was achieved in 9 out of 13 tests and significant correlations of the volumetric strains were obtained throughout the range of applied axial compression. Interestingly, the stepwise propagating localization zones in trabecular bone converged to the buckling locations in the cortical shell. While the adopted continuum finite element approach still suffers from several limitations, these encouraging preliminary results towardsthe prediction of extended vertebral collapse may help in assessing fracture stability in future work.

Metabolomics and its potential in drug development

Metabolomics is the global and unbiased survey of the complement of small molecules (say, <1 kDa) in a biofluid, tissue, organ or organism and measures the end-products of the cellular metabolism of both endogenous and exogenous substrates. Many drug candidates fail during Phase II and III clinical trials at an enormous cost to the pharmaceutical industry in terms of both time lost and of financial resources. The constantly evolving model of drug development now dictates that biomarkers should be employed in preclinical development for the early detection of likely-to-fail candidates. Biomarkers may also be useful in the preselection of patients and through the subclassification of diseases in clinical drug development. Here we show with examples how metabolomics can assist in the preclinical development phases of discovery, pharmacology, toxicology, and ADME. Although not yet established as a clinical trial patient prescreening procedure, metabolomics shows considerable promise in this regard. We can be certain that metabolomics will join genomics and transcriptomics in lubricating the wheels of clinical drug development in the near future.

Professional musicians listen differently to music

INTRODUCTION: Experience-based adaptation of emotional responses is an important faculty for cognitive and emotional functioning. Professional musicians represent an ideal model in which to elicit experience-driven changes in the emotional processing domain. The changes of the central representation of emotional arousal due to musical expertise are still largely unknown. The aim of the present study was to investigate the electroencephalogram (EEG) correlates of experience-driven changes in the domain of emotional arousal. Therefore, the differences in perceived (subjective arousal via ratings) and physiologically measured (EEG) arousal between amateur and professional musicians were examined. PROCEDURE: A total of 15 professional and 19 amateur musicians listened to the first movement of Ludwig van Beethoven's 5th symphony (duration=∼7.4min), during which a continuous 76-channel EEG was recorded. In a second session, the participants evaluated their emotional arousal during listening. In a tonic analysis, we examined the average EEG data over the time course of the music piece. For a phasic analysis, a fast Fourier transform was performed and covariance maps of spectral power were computed in association with the subjective arousal ratings. RESULTS: The subjective arousal ratings of the professional musicians were more consistent than those of the amateur musicians. In the tonic EEG analysis, a mid-frontal theta activity was observed in the professionals. In the phasic EEG, the professionals exhibited an increase of posterior alpha, central delta, and beta rhythm during high arousal. DISCUSSION: Professionals exhibited different and/or more intense patterns of emotional activation when they listened to the music. The results of the present study underscore the impact of music experience on emotional reactions.