DIRAC framework evaluation for the Fermi\boldsymbol{Fermi}-LAT and CTA experiments

DIRAC (Distributed Infrastructure with Remote Agent Control) is a general framework for the management of tasks over distributed heterogeneous computing environments. It has been originally developed to support the production activities of the LHCb (Large Hadron Collider Beauty) experiment and today is extensively used by several particle physics and biology communities. Current ($Fermi$ Large Area Telescope -- LAT) and planned (Cherenkov Telescope Array -- CTA) new generation astrophysical/cosmological experiments, with very large processing and storage needs, are currently investigating the usability of DIRAC in this context. Each of these use cases has some peculiarities: $Fermi$-LAT will interface DIRAC to its own workflow system to allow the access to the grid resources, while CTA is using DIRAC as workflow management system for Monte Carlo production and analysis on the grid. We describe the prototype effort that we lead toward deploying a DIRAC solution for some aspects of $Fermi$-LAT and CTA needs.Comment: proceedings to CHEP 2013 conference : http://www.chep2013.org

Three-Dimensional Printed Abdominal Imaging Windows for In Vivo Imaging of Deep-Lying Tissues

The ability to microscopically image diseased or damaged tissue throughout a longitudinal study in living mice would provide more insight into disease progression than having just a couple of time points to study. In vivo disease development and monitoring provides more insight than in vitro studies as well. In this study, we developed permanent 3D-printed, surgically implantable abdominal imaging windows (AIWs) to allow for longitudinal imaging of deep-lying tissues or organs in the abdominal cavity of living mice. They are designed to prevent organ movement while allowing the animal to behave normally throughout longitudinal studies. The AIW also acts as its own mounting bracket for attaching them to a custom 3D printed microscope mount that attaches to the stage of a microscope and houses the animal inside. During the imaging of the living animal, cellular and macroscopic changes over time in one location can be observed because markers can be used to find the same spot in each imaging session. We were able to deliver cancer cells to the pancreas and use the AIW to image the disease progression. The design of the AIWs can be expanded to include secondary features, such as delivery and manipulation ports and guides, and to make windows for imaging the brain, subcutaneous implants, and mammary tissue. In all, these 3D-printed AIWs and their microscope mount provide a system for enhancing the ability to image and study cellular and disease progression of deep-lying abdominal tissues of living animals during longitudinal studies

Die REGIONALEN als Instrument regionalisierter Strukturpolitik in Nordrhein-Westfalen - das Beispiel der REGIONALE 2010 Köln/Bonn

Der Beitrag beschäftigt sich mit den REGIONALEN in Nordrhein-Westfalen als Instrument regionalisierter Strukturpolitik. Im Rahmen der mittlerweile sechsten REGIONALEN präsentiert die Region Köln/Bonn im Jahr 2010 die Ergebnisse eines mehrjährigen Kooperationsprozesses. Die „Zukunftssicherung“ wurde zum zentralen Thema des zeitlich befristeten, projektorientierten Ansatzes gemacht. Bei den beteiligten Akteuren und der Öffentlichkeit konnte sich die REGIONALE 2010 als positives Schlüsselsymbol etablieren. Als Erfolgsfaktoren lassen sich die Organisations- und Kooperationsstrukturen, die Förderung und gebaute bzw. erlebbare Erfolge sowie deren Vermarktbarkeit identifizieren. Mit hohem Aufwand gelingt es, in der heterogenen Region ein gemeinsames Agieren vieler zentraler Akteure zu erzeugen, was sich auch in der frühzeitigen Festlegung auf eine Nachfolgestruktur manifestiert. Die Chancen stehen gut, dass die im Rahmen der „Institutionalisierung auf Zeit“ geschaffenen Grundlagen sowohl auf der Projekt- als auch auf der programmatischen und organisatorischen Ebene über das Präsentationsjahr hinaus tragen.This paper is concerned with the programme of REGIONALE events organised in North Rhine-Westphalia as an instrument of regionalised structure policy. Within the framework of what is now the sixth REGIONALE, in 2010 the Cologne/Bonn region will present the results of a process of co-operation which stretches back over many years. The central theme chosen for this project-based and time-limited programme is “Safeguarding the Future”. REGIONALE 2010 has been able to establish itself both among the actors involved and among the general public as a positive and emblematic symbol. The factors behind its success can be identified as the organisational and co-operative structures it employs, the funding it receives, as well as the physical and tangible successes it presents, and the manner in which they are marketed. With a great deal of effort, and at considerable expense, the REGIONALE is able to generate joint action within this heterogeneous region on the part of a host of key actors; this is manifested not least in the success in deciding on a follow-up structure at a relatively early point in the process. There is every likelihood that the foundation which was established as part of what is termed “long-term institutionalisation” – both at the project level and at the programme and organisational level – will remain in place after the presentation year comes to an end

Influenza virus differentially activates mTORC1 and mTORC2 signaling to maximize late stage replication

<div><p>Influenza A virus usurps host signaling factors to regulate its replication. One example is mTOR, a cellular regulator of protein synthesis, growth and motility. While the role of mTORC1 in viral infection has been studied, the mechanisms that induce mTORC1 activation and the substrates regulated by mTORC1 during influenza virus infection have not been established. In addition, the role of mTORC2 during influenza virus infection remains unknown. Here we show that mTORC2 and PDPK1 differentially phosphorylate AKT upon influenza virus infection. PDPK1-mediated phoshorylation of AKT at a distinct site is required for mTORC1 activation by influenza virus. On the other hand, the viral NS1 protein promotes phosphorylation of AKT at a different site via mTORC2, which is an activity dispensable for mTORC1 stimulation but known to regulate apoptosis. Influenza virus HA protein and down-regulation of the mTORC1 inhibitor REDD1 by the virus M2 protein promote mTORC1 activity. Systematic phosphoproteomics analysis performed in cells lacking the mTORC2 component Rictor in the absence or presence of Torin, an inhibitor of both mTORC1 and mTORC2, revealed mTORC1-dependent substrates regulated during infection. Members of pathways that regulate mTORC1 or are regulated by mTORC1 were identified, including constituents of the translation machinery that once activated can promote translation. mTORC1 activation supports viral protein expression and replication. As mTORC1 activation is optimal midway through the virus life cycle, the observed effects on viral protein expression likely support the late stages of influenza virus replication when infected cells undergo significant stress.</p></div

Absolute treatment effects of novel antidiabetic drugs on a composite renal outcome: meta-analysis of digitalized individual patient data

Background: Absolute treatment benefits—expressed as numbers needed to treat—of the glucose lowering and cardiovascular drugs, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose transporter 2 (SGLT2) inhibitors on renal outcomes remain uncertain. With the present meta-analysis of digitalized individual patient data, we aimed to display and compare numbers needed to treat of both drugs on a composite renal outcome. Methods: From Kaplan–Meier plots of major cardiovascular outcome trials of GLP-1 receptor agonists and SGLT2 inhibitors vs. placebo, we digitalized individual patient time-to-event information on composite renal outcomes with WebPlotDigitizer 4.2; numbers needed to treat from individual cardiovascular outcome trials were estimated using parametric Weibull regression models and compared to original data. Random-effects meta-analysis generated meta-numbers needed to treat with 95% confidence intervals (CI). Results: Twelve cardiovascular outcome trials (three for GLP-1 receptor agonists, nine for SGLT2 inhibitors) comprising 90,865 participants were included. Eight trials were conducted in primary type 2 diabetes populations, two in a primary heart failure and two in a primary chronic kidney disease population. Mean estimated glomerular filtration rate at baseline ranged between 37.3 and 85.3 ml/min/1.73 m2. Meta-analyses estimated meta-numbers needed to treat of 85 (95% CI 60; 145) for GLP-1 receptor agonists and 104 (95% CI 81; 147) for SGLT2 inhibitors for the composite renal outcome at the overall median follow-up time of 36 months. Conclusion: The present meta-analysis of digitalized individual patient data revealed moderate and similar absolute treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors compared to placebo for a composite renal outcome. Graphical Abstract

Assessing the potential for precision medicine in body weight reduction with regard to type 2 diabetes mellitus therapies: A meta‐regression analysis of 120 randomized controlled trials

Aims: To assess the potential for precision medicine in type 2 diabetes by quantifying the variability of body weight as response to pharmacological treatment and to identify predictors which could explain this variability. Methods: We used randomized clinical trials (RCTs) comparing glucose‐lowering drugs (including but not limited to sodium‐glucose cotransporter‐2 inhibitors, glucagon‐like peptide‐1 receptor agonists and thiazolidinediones) to placebo from four recent systematic reviews. RCTs reporting on body weight after treatment to allow for calculation of its logarithmic standard deviation (log[SD], i.e., treatment response heterogeneity) in verum (i.e., treatment) and placebo groups were included. Meta‐regression analyses were performed with respect to variability of body weight after treatment and potential predictors. Results: A total of 120 RCTs with a total of 43 663 participants were analysed. A slightly larger treatment response heterogeneity was shown in the verum groups, with a median log(SD) of 2.83 compared to 2.79 from placebo. After full adjustment in the meta‐regression model, the difference in body weight log(SD) was −0.026 (95% confidence interval −0.044; 0.008), with greater variability in the placebo groups. Scatterplots did not show any slope divergence (i.e., interaction) between clinical predictors and the respective treatment (verum or placebo). Conclusions: We found no major treatment response heterogeneity in RCTs of glucose‐lowering drugs for body weight reduction in type 2 diabetes. The precision medicine approach may thus be of limited value in this setting

SERS spectroscopy with machine learning to analyze human plasma derived sEVs for coronary artery disease diagnosis and prognosis

Coronary artery disease (CAD) is one of the major cardiovascular diseases and represents the leading causes of global mortality. Developing new diagnostic and therapeutic approaches for CAD treatment are critically needed, especially for an early accurate CAD detection and further timely intervention. In this study, we successfully isolated human plasma small extracellular vesicles (sEVs) from four stages of CAD patients, that is, healthy control, stable plaque, non-ST-elevation myocardial infarction, and ST-elevation myocardial infarction. Surface-enhanced Raman scattering (SERS) measurement in conjunction with five machine learning approaches, including Quadratic Discriminant Analysis, Support Vector Machine (SVM), K-Nearest Neighbor, Artificial Neural network, were then applied for the classification and prediction of the sEV samples. Among these five approaches, the overall accuracy of SVM shows the best predication results on both early CAD detection (86.4%) and overall prediction (92.3%). SVM also possesses the highest sensitivity (97.69%) and specificity (95.7%). Thus, our study demonstrates a promising strategy for noninvasive, safe, and high accurate diagnosis for CAD early detection

Association of a lifestyle score with cardiometabolic markers among individuals with diabetes: a cross-sectional study

Introduction To investigate the associations of a lifestyle score with various cardiovascular risk markers, indicators for fatty liver disease as well as MRI-determined total, subcutaneous and visceral adipose tissue mass in adults with new-onset diabetes. Research design and methods This cross-sectional analysis included 196 individuals with type 1 (median age: 35 years; median body mass index (BMI): 24 kg/m²) and 272 with type 2 diabetes (median age: 53 years; median BMI: 31 kg/m²) from the German Diabetes Study. A healthy lifestyle score was generated based on healthy diet, moderate alcohol consumption, recreational activity, non-smoking and non-obese BMI. These factors were summed to form a score ranging from 0 to 5. Results In total, 8.1% of the individuals adhered to none or one, 17.7% to two, 29.7% to three, 26.7% to four, and 17.7% to all five favorable lifestyle factors. High compared with low adherence to the lifestyle score was associated with more favorable outcome measures, including triglycerides (β (95% CI) -49.1 mg/dL (-76.7; -21.4)), low-density lipoprotein (-16.7 mg/dL (-31.3; -2.0)), and high-density lipoprotein cholesterol (13.5 mg/dL (7.6; 19.4)), glycated hemoglobin (-0.5% (-0.8%; -0.1%)), high-sensitivity C reactive protein (-0.4 mg/dL (-0.6; -0.2)), as well as lower hepatic fat content (-8.3% (-11.9%; -4.7%)), and visceral adipose tissue mass (-1.8 dm³ (-2.9; -0.7)). The dose-response analyses showed that adherence to every additional healthy lifestyle factor was associated with more beneficial risk profiles. Conclusions Adherence to each additional healthy lifestyle factor was beneficially associated with cardiovascular risk markers, indicators of fatty liver disease and adipose tissue mass. Strongest associations were observed for adherence to all healthy lifestyle factors in combination. Trial registration number NCT01055093

ES2008-54271 Simulation, Analysis and Systems Engineering of a Hybrid-Electric Race Car

ABSTRACT For the past two years, Embry-Riddle has participated in the SAE Formula Hybrid competition. As part of the competition, a team of students analyze, design, and build a fully functional hybrid-electric race car. As an academic competition, the event is designed to allow a wide variety of system configurations and fuel choices. In order to optimize the vehicle characteristics, simulate vehicle performance, and build control laws, the design team created a Simulink model of the race car. As a recently created design competition, the SAE Formula Hybrid event offers an opportunity for both design innovation and system engineering. To develop a concept for the competition, the ERAU team developed detailed simulations of the vehicle in Simulink. Since the competition allows a variety of energy storage devices, engines, fuels, driveline configurations, and control systems, the development of a system dynamics model was not straight-forward. Further, system components for this project are constrained by some rules and practical constraints. The vehicle configuration was selected to be a parallel hybrid using a 250cc gasoline engine and 7.2kW DC motor with 1500F ultra-capacitor energy storage, with an unusual control strategy. The results of the Simulink model were used to predict how this vehicle configuration compares to other design choices including alternative fuels, energy storage devices and control strategies. The performance of the actual vehicle at the 2008 SAE Formula Hybrid competition, which occurs May 2008, will be presented at the conference