Fully automatic worst-case execution time analysis for MATLAB/Simulink models

“This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder." “Copyright IEEE. Personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution to servers or lists, or to reuse any copyrighted component of this work in other works must be obtained from the IEEE.”In today's technical world (e.g., in the automotive industry), more and more purely mechanical components get replaced by electro-mechanical ones. Thus the size and complexity of embedded systems steadily increases. To cope with this development, comfortable software engineering tools are being developed that allow a more functionality-oriented development of applications. The paper demonstrates how worst-case execution time (WCET) analysis is integrated into such a high-level application design and simulation tool MATLAB/Simulink-thus providing a higher-level interface to WCET analysis. The MATLAB/Simulink extensions compute and display worst-case timing data for all blocks of a MATLAB/Simulink simulation, which gives the developer of an application valuable feedback about the correct timing of the application being developed. The solution facilitates a fully-automated WCET analysis, i.e., in contrast to existing approaches the programmer does not have to provide path information

Frustration in fuzzy protein complexes leads to interaction versatility

Disordered proteins frequently serve as interaction hubs involving a constrained variety of partners. Complexes with different partners frequently exhibit distinct binding modes, involving regions that remain disordered in the bound state. While the conformational properties of disordered proteins are well-characterized in their free states, less is known about the molecular mechanisms by which specificity can be achieved not with one but with multiple partners. Using the energy landscape theory concept of protein frustration, we demonstrate that complexes of disordered proteins exhibit a high degree of local frustration, especically at the binding interface. These suboptimal interactions lead to the possibility of multiple bound substates, each displaying distinct frustration patterns, which are differently populated in complexes with different partners. These results explain how specificity of disordered proteins can be achieved without a single common bound conformation and how the confliict between different interactions can be used to control the binding to multiple partners

Tradeoffs in Model Performance and Effort for Long-Term Phosphorus Leaching Based on In Situ Field Data

Phosphorus and N are critical nutrients for agriculture but are also responsible for surface water enrichment that leads to toxic algal growth. Although P loading to surface waters has traditionally been thought to occur primarily in surface runoff, contributions from subsurface transport can also be significant. The primary objectives of this research were to evaluate several methods of representing macropore flow and transport in a finite element model using plot-scale infiltration and leaching data and to compare several models of various levels of complexity to simulate long-term P leaching. To determine flow and transport parameters, single- and dual-porosity models in HYDRUS-2D were calibrated with infiltration, Cl−, and P data from a 22-h plot-scale leaching experiment on a silt loam mantle with gravel subsoil. Both homogeneous and heterogeneous gravel profiles were simulated. The dual-porosity model with heterogeneous hydraulic conductivity best matched experimental data, with physical nonequilibrium (dual porosity) being more important than two-dimensional (2D) heterogeneity. Long-term (9 yr) P leaching to the water table (3 m below the soil surface) at the field site was simulated with both one-dimensional (1D) and 2D models using the calibrated parameters. There was little difference between analogous 1D and 2D models, suggesting that HYDRUS-1D may be sufficient to model long-term P leaching. Overall, the most important elements for accurately simulating P leaching in this silt loam and gravel soil profile were found to be (i) field-measured hydraulic conductivity of the limiting soil layer, (ii) calibrated dispersivity, and (iii) dual-porosity, in some circumstances

An interdisciplinary intervention to prevent falls in community-dwelling elderly persons: protocol of a cluster-randomized trial [PreFalls]

<p>Abstract</p> <p>Background</p> <p>Prevention of falls in the elderly is a public health target in many countries around the world. While a large number of trials have investigated the effectiveness of fall prevention programs, few focussed on interventions embedded in the general practice setting and its related network. In the Prevent Falls (PreFalls) trial we aim to investigate the effectiveness of a pre-tested multi-modal intervention compared to usual care in this setting.</p> <p>Methods/Design</p> <p>PreFalls is a controlled multicenter prospective study with cluster-randomized allocation of about 40 general practices to an experimental or a control group. We aim to include 382 community dwelling persons aged 65 and older with an increased risk of falling. All participating general practitioners are trained to systematically assess the risk of falls using a set of validated tests. Patients from intervention practices are invited to participate in a 16-weeks exercise program with focus on fall prevention delivered by specifically trained local physiotherapists. Patients from practices allocated to the control group receive usual care. Main outcome measure is the number of falls per individual in the first 12 months (analysis by negative binomial regression). Secondary outcomes include falls in the second year, the proportion of participants falling in the first and the second year, falls associated with injury, risk of falls, fear of falling, physical activity and quality of life.</p> <p>Discussion</p> <p>Reducing falls in the elderly remains a major challenge. We believe that with its strong focus on a both systematic and realistic fall prevention strategy adapted to primary care setting PreFalls will be a valuable addition to the scientific literature in the field.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01032252">NCT01032252</a></p

Does Sea Spray Aerosol Contribute Significantly To Aerosol Trace Element Loading? A Case Study From the U.S. GEOTRACES Pacific Meridional Transect (GP15)

Atmospheric deposition represents a major input for micronutrient trace elements (TEs) to the surface ocean and is often quantified indirectly through measurements of aerosol TE concentrations. Sea spray aerosol (SSA) dominates aerosol mass concentration over much of the global ocean, but few studies have assessed its contribution to aerosol TE loading, which could result in overestimates of “new” TE inputs. Low-mineral aerosol concentrations measured during the U.S. GEOTRACES Pacific Meridional Transect (GP15; 152°W, 56°N to 20°S), along with concurrent towfish sampling of surface seawater, provided an opportunity to investigate this aspect of TE biogeochemical cycling. Central Pacific Ocean surface seawater Al, V, Mn, Fe, Co, Ni, Cu, Zn, and Pb concentrations were combined with aerosol Na data to calculate a “recycled” SSA contribution to aerosol TE loading. Only vanadium was calculated to have a SSA contribution averaging \u3e1% along the transect (mean of 1.5%). We derive scaling factors from previous studies on TE enrichments in the sea surface microlayer and in freshly produced SSA to assess the broader potential for SSA contributions to aerosol TE loading. Maximum applied scaling factors suggest that SSA could contribute significantly to the aerosol loading of some elements (notably V, Cu, and Pb), while for others (e.g., Fe and Al), SSA contributions largely remaine

Self-homodyne tomography of a twin-beam state

A self-homodyne detection scheme is proposed to perform two-mode tomography on a twin-beam state at the output of a nondegenerate optical parametric amplifier. This scheme has been devised to improve the matching between the local oscillator and the signal modes, which is the main limitation to the overall quantum efficiency in conventional homodyning. The feasibility of the measurement is analyzed on the basis of Monte-Carlo simulations, studying the effect of non-unit quantum efficiency on detection of the correlation and the total photon-number oscillations of the twin-beam state.Comment: 13 pages (two-column ReVTeX) including 21 postscript figures; to appear on Phys. Rev.

Comparison of the characteristics at diagnosis and treatment of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries

Background and aims: For children with heterozygous familial hypercholesterolaemia (HeFH), European guidelines recommend consideration of statin therapy by age 8–10 years for those with a low density lipoprotein cholesterol (LDL-C) >3.5 mmol/l, and dietary and lifestyle advice. Here we compare the characteristics and lipid levels in HeFH children from Norway, UK, Netherlands, Belgium, Czech Republic, Austria, Portugal and Greece. Methods: Fully-anonymized data were analysed at the London centre. Differences in registration and on treatment characteristics were compared by standard statistical tests. Results: Data was obtained from 3064 children. The median age at diagnosis differed significantly between countries (range 3–11 years) reflecting differences in diagnostic strategies. Mean (SD) LDL-C at diagnosis was 5.70 (±1.4) mmol/l, with 88% having LDL-C>4.0 mmol/l. The proportion of children older than 10 years at follow-up who were receiving statins varied significantly (99% in Greece, 56% in UK), as did the proportion taking Ezetimibe (0% in UK, 78% in Greece). Overall, treatment reduced LDL-C by between 28 and 57%, however, in those >10 years, 23% of on-treatment children still had LDL-C>3.5 mmol/l and 66% of those not on a statin had LDL-C>3.5 mmol/l. Conclusions: The age of HeFH diagnosis in children varies significantly across 8 countries, as does the proportion of those >10 years being treated with statin and/or ezetimibe. Approximately a quarter of the treated children and almost three quarters of the untreated children older than 10 years still have LDL-C concentrations over 3.5 mmol/l. These data suggest that many children with FH are not receiving the full potential benefit of early identification and appropriate lipid-lowering treatment according to recommendations

The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification

PURPOSE: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for sequence-level variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource Familial Hypercholesterolemia (FH) Variant Curation Expert Panel was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. In this study, we provide consensus recommendations for the most common FH-associated gene, LDLR, where >2300 unique FH-associated variants have been identified. METHODS: The multidisciplinary FH Variant Curation Expert Panel met in person and through frequent emails and conference calls to develop LDLR-specific modifications of ACMG/AMP guidelines. Through iteration, pilot testing, debate, and commentary, consensus among experts was reached. RESULTS: The consensus LDLR variant modifications to existing ACMG/AMP guidelines include (1) alteration of population frequency thresholds, (2) delineation of loss-of-function variant types, (3) functional study criteria specifications, (4) cosegregation criteria specifications, and (5) specific use and thresholds for in silico prediction tools, among others. CONCLUSION: Establishment of these guidelines as the new standard in the clinical laboratory setting will result in a more evidence-based, harmonized method for LDLR variant classification worldwide, thereby improving the care of patients with FH