An improved method for embryogenic suspension cultures of 'Richter 110' rootstock

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Stochastic virtual tests for fiber composites

We will describe a Virtual Test system for continuous fiber composites. The virtual test draws from a new wave of advanced experiments and theory that address physical, mathematical, and engineering aspects of material definition and failure prediction. The methods go far beyond currently standard tests and conventional FEM analysis to challenge our conception of what can constitute a practicable engineering approach. Emphasis will be given to high temperature ceramic matrix composites with textile reinforcement, which have been the subject material of the National Hypersonic Science Center, Materials and Structures, a joint AFOSR/NASA program. However, thematic topics also address generic fiber composites. Development has been organized as a “pipeline” that links the separate disciplinary efforts of groups housed in seven institutions spread across the United States. The main research steps are: high resolution three-dimensional (3D) imaging of the microstructure, statistical characterization of the microstructure, formulation of a probabilistic generator for creating virtual specimens that replicate the measured statistics, creation of a computational model for a virtual specimen that allows general representation of discrete damage events, calibration of the model using room and high temperature tests, simulation of failure, and model validation. Key new experiments include digital surface image correlation and µm-resolution 3D computed tomography imaging of the microstructure and evolving damage, both executed at temperatures exceeding 1500°C. Conceptual advances include using both geometry and topology to characterize stochastic microstructures. Computational methods include new probabilistic algorithms for generating stochastic virtual specimens and a new Augmented Finite Element Method that yields extreme efficiency in dealing with arbitrary cracking in heterogeneous materials. The challenge of relating variance in engineering properties to stochastic microstructure in a computationally tractable manner, while retaining necessary physical details in models, will be discussed

Mechanical metamaterials at the theoretical limit of isotropic elastic stiffness

Acknowledgements H.N.G.W. is grateful for support for this work by the ONR (grant number N00014-15-1-2933), managed by D. Shifler, and the DARPA MCMA programme (grant number W91CRB-10-1-005), managed by J. Goldwasser.Peer reviewedPostprintPostprintPostprintPostprin

Large-Scale Assessment of the Zebrafish Embryo as a Possible Predictive Model in Toxicity Testing

Background: In the drug discovery pipeline, safety pharmacology is a major issue. The zebrafish has been proposed as a model that can bridge the gap in this field between cell assays (which are cost-effective, but low in data content) and rodent assays (which are high in data content, but less cost-efficient). However, zebrafish assays are only likely to be useful if they can be shown to have high predictive power. We examined this issue by assaying 60 water-soluble compounds representing a range of chemical classes and toxicological mechanisms. Methodology/Principal Findings: Over 20,000 wild-type zebrafish embryos (including controls) were cultured individually in defined buffer in 96-well plates. Embryos were exposed for a 96 hour period starting at 24 hours post fertilization. A logarithmic concentration series was used for range-finding, followed by a narrower geometric series for LC 50 determination. Zebrafish embryo LC50 (log mmol/L), and published data on rodent LD50 (log mmol/kg), were found to be strongly correlated (using Kendall’s rank correlation tau and Pearson’s product-moment correlation). The slope of the regression line for the full set of compounds was 0.73403. However, we found that the slope was strongly influenced by compound class. Thus, while most compounds had a similar toxicity level in both species, some compounds were markedly more toxic in zebrafish than in rodents, or vice versa. Conclusions: For the substances examined here, in aggregate, the zebrafish embryo model has good predictivity for toxicit

INDIGO-DataCloud: a Platform to Facilitate Seamless Access to E-Infrastructures

[EN] This paper describes the achievements of the H2020 project INDIGO-DataCloud. The project has provided e-infrastructures with tools, applications and cloud framework enhancements to manage the demanding requirements of scientific communities, either locally or through enhanced interfaces. The middleware developed allows to federate hybrid resources, to easily write, port and run scientific applications to the cloud. In particular, we have extended existing PaaS (Platform as a Service) solutions, allowing public and private e-infrastructures, including those provided by EGI, EUDAT, and Helix Nebula, to integrate their existing services and make them available through AAI services compliant with GEANT interfederation policies, thus guaranteeing transparency and trust in the provisioning of such services. Our middleware facilitates the execution of applications using containers on Cloud and Grid based infrastructures, as well as on HPC clusters. Our developments are freely downloadable as open source components, and are already being integrated into many scientific applications.INDIGO-Datacloud has been funded by the European Commision H2020 research and innovation program under grant agreement RIA 653549.Salomoni, D.; Campos, I.; Gaido, L.; Marco, J.; Solagna, P.; Gomes, J.; Matyska, L.... (2018). INDIGO-DataCloud: a Platform to Facilitate Seamless Access to E-Infrastructures. Journal of Grid Computing. 16(3):381-408. https://doi.org/10.1007/s10723-018-9453-3S381408163García, A.L., Castillo, E.F.-d., Puel, M.: Identity federation with VOMS in cloud infrastructures. In: 2013 IEEE 5Th International Conference on Cloud Computing Technology and Science, pp 42–48 (2013)Chadwick, D.W., Siu, K., Lee, C., Fouillat, Y., Germonville, D.: Adding federated identity management to OpenStack. Journal of Grid Computing 12(1), 3–27 (2014)Craig, A.L.: A design space review for general federation management using keystone. In: Proceedings of the 2014 IEEE/ACM 7th International Conference on Utility and Cloud Computing, pp 720–725. IEEE Computer Society (2014)Pustchi, N., Krishnan, R., Sandhu, R.: Authorization federation in iaas multi cloud. In: Proceedings of the 3rd International Workshop on Security in Cloud Computing, pp 63–71. ACM (2015)Lee, C.A., Desai, N., Brethorst, A.: A Keystone-Based Virtual Organization Management System. In: 2014 IEEE 6Th International Conference On Cloud Computing Technology and Science (Cloudcom), pp 727–730. IEEE (2014)Castillo, E.F.-d., Scardaci, D., García, A.L.: The EGI Federated Cloud e-Infrastructure. Procedia Computer Science 68, 196–205 (2015)AARC project: AARC Blueprint Architecture, see https://aarc-project.eu/architecture . Technical report (2016)Oesterle, F., Ostermann, S., Prodan, R., Mayr, G.J.: Experiences with distributed computing for meteorological applications: grid computing and cloud computing. Geosci. Model Dev. 8(7), 2067–2078 (2015)Plasencia, I.C., Castillo, E.F.-d., Heinemeyer, S., García, A.L., Pahlen, F., Borges, G.: Phenomenology tools on cloud infrastructures using OpenStack. The European Physical Journal C 73(4), 2375 (2013)Boettiger, C.: An introduction to docker for reproducible research. ACM SIGOPS Operating Systems Review 49(1), 71–79 (2015)Docker: http://www.docker.com (2013)Gomes, J., Campos, I., Bagnaschi, E., David, M., Alves, L., Martins, J., Pina, J., Alvaro, L.-G., Orviz, P.: Enabling rootless linux containers in multi-user environments: the udocker tool. Computing Physics Communications. https://doi.org/10.1016/j.cpc.2018.05.021 (2018)Zhang, Z., Chuan, W., Cheung, D.W.L.: A survey on cloud interoperability taxonomies, standards, and practice. SIGMETRICS perform. Eval. Rev. 40(4), 13–22 (2013)Lorido-Botran, T., Miguel-Alonso, J., Lozano, J.A.: A Review of Auto-scaling Techniques for Elastic Applications in Cloud Environments. Journal of Grid Computing 12(4), 559–592 (2014)Nyrén, R., Metsch, T., Edmonds, A., Papaspyrou, A.: Open Cloud Computing Interface–Core. Technical report, Open Grid Forum (2010)Metsch, T., Edmonds, A.: Open Cloud Computing Interface-Infrastructure. Technical report, Open Grid Forum (2010)Metsch, T., Edmonds, A.: Open Cloud Computing Interface-RESTful HTTP Rendering. Technical report, Open Grid Forum (2011)(Ca Technologies) Lipton, P., (Ibm) Moser, S., (Vnomic) Palma, D., (Ibm) Spatzier, T.: Topology and Orchestration Specification for Cloud Applications. Technical report, OASIS Standard (2013)Teckelmann, R., Reich, C., Sulistio, A.: Mapping of cloud standards to the taxonomy of interoperability in IaaS. In: Proceedings - 2011 3rd IEEE International Conference on Cloud Computing Technology and Science, CloudCom 2011, pp 522–526 (2011)García, A.L., Castillo, E.F.-d., Fernández, P.O.: Standards for enabling heterogeneous IaaS cloud federations. Computer Standards & Interfaces 47, 19–23 (2016)Caballer, M., Zala, S., García, A.L., Montó, G., Fernández, P.O., Velten, M.: Orchestrating complex application architectures in heterogeneous clouds. Journal of Grid Computing 16 (1), 3–18 (2018)Hardt, M., Jejkal, T., Plasencia, I.C., Castillo, E.F.-d., Jackson, A., Weiland, M., Palak, B., Plociennik, M., Nielsson, D.: Transparent Access to Scientific and Commercial Clouds from the Kepler Workflow Engine. Computing and Informatics 31(1), 119 (2012)Fakhfakh, F., Kacem, H.H., Kacem, A.H.: Workflow Scheduling in Cloud Computing a Survey. In: IEEE 18Th International Enterprise Distributed Object Computing Conference Workshops and Demonstrations (EDOCW), 2014, Vol. 71, pp. 372–378. Springer, New York (2014)Stockton, D.B., Santamaria, F.: Automating NEURON simulation deployment in cloud resources. Neuroinformatics 15(1), 51–70 (2017)Plóciennik, M., Fiore, S., Donvito, G., Owsiak, M., Fargetta, M., Barbera, R., Bruno, R., Giorgio, E., Williams, D.N., Aloisio, G.: Two-level Dynamic Workflow Orchestration in the INDIGO DataCloud for Large-scale, Climate Change Data Analytics Experiments. Procedia Computer Science 80, 722–733 (2016)Moreno-Vozmediano, R., Montero, R.S., Llorente, I.M.: Multicloud deployment of computing clusters for loosely coupled mtc applications. IEEE transactions on parallel and distributed systems 22(6), 924–930 (2011)Katsaros, G., Menzel, M., Lenk, A.: Cloud Service Orchestration with TOSCA, Chef and Openstack. In: Ic2e (2014)Garcia, A.L., Zangrando, L., Sgaravatto, M., Llorens, V., Vallero, S., Zaccolo, V., Bagnasco, S., Taneja, S., Dal Pra, S., Salomoni, D., Donvito, G.: Improved Cloud resource allocation: how INDIGO-DataCloud is overcoming the current limitations in Cloud schedulers. J. Phys. Conf. Ser. 898(9), 92010 (2017)Singh, S., Chana, I.: A survey on resource scheduling in cloud computing issues and challenges. Journal of Grid Computing, pp. 1–48 (2016)García, A.L., Castillo, E.F.-d., Fernández, P.O., Plasencia, I.C., de Lucas, J.M.: Resource provisioning in Science Clouds: Requirements and challenges. Software: Practice and Experience 48(3), 486–498 (2018)Chauhan, M.A., Babar, M.A., Benatallah, B.: Architecting cloud-enabled systems: a systematic survey of challenges and solutions. Software - Practice and Experience 47(4), 599–644 (2017)Somasundaram, T.S., Govindarajan, K.: CLOUDRB A Framework for scheduling and managing High-Performance Computing (HPC) applications in science cloud. Futur. Gener. Comput. Syst. 34, 47–65 (2014)Sotomayor, B., Keahey, K., Foster, I.: Overhead Matters: A Model for Virtual Resource Management. In: Proceedings of the 2nd International Workshop on Virtualization Technology in Distributed Computing SE - VTDC ’06, p 5. IEEE Computer Society, Washington (2006)SS, S.S., Shyam, G.K., Shyam, G.K.: Resource management for Infrastructure as a Service (IaaS) in cloud computing SS Manvi A survey. J. Netw. Comput. Appl. 41, 424–440 (2014)INDIGO-DataCloud consortium: Initial requirements from research communities - d2.1, see https://www.indigo-datacloud.eu/documents/initial-requirements-research-communities-d21 https://www.indigo-datacloud.eu/documents/initial-requirements-research-communities-d21 https://www.indigo-datacloud.eu/documents/initial-requirements-research-communities-d21 . Technical report (2015)Europen open science cloud: https://ec.europa.eu/research/openscience (2015)Proot: https://proot-me.github.io/ (2014)Runc: https://github.com/opencontainers/runc (2016)Fakechroot: https://github.com/dex4er/fakechroot (2015)Pérez, A., Moltó, G., Caballer, M., Calatrava, A.: Serverless computing for container-based architectures Future Generation Computer Systems (2018)de Vries, K.J.: Global fits of supersymmetric models after LHC run 1. Phd thesis Imperial College London (2015)Openstack: https://www.openstack.org/ (2015)See http://argus-documentation.readthedocs.io/en/stable/argus_introduction.html (2017)See https://en.wikipedia.org/wiki/xacml (2013)See http://www.simplecloud.info (2014)Opennebula: http://opennebula.org/ (2018)Redhat openshift: http://www.opencityplatform.eu (2011)The cloud foundry foundation: https://www.cloudfoundry.org/ (2015)Caballer, M., Blanquer, I., Moltó, G., de Alfonso, C.: Dynamic management of virtual infrastructures. Journal of Grid Computing 13(1), 53–70 (2015)See http://www.infoq.com/articles/scaling-docker-with-kubernetes http://www.infoq.com/articles/scaling-docker-with-kubernetes (2014)Prisma project: http://www.ponsmartcities-prisma.it/ (2010)Opencitiy platform: http://www.opencityplatform.eu (2014)Onedata: https://onedata.org/ (2018)Dynafed: http://lcgdm.web.cern.ch/dynafed-dynamic-federation-project http://lcgdm.web.cern.ch/dynafed-dynamic-federation-project (2011)Fts3: https://svnweb.cern.ch/trac/fts3 (2011)Fernández, P.O., García, A.L., Duma, D.C., Donvito, G., David, M., Gomes, J.: A set of common software quality assurance baseline criteria for research projects, see http://hdl.handle.net/10261/160086 . Technical reportHttermann, M.: Devops for developers Apress (2012)EOSC-Hub: ”Integrating and managing services for the European Open Science Cloud” Funded by H2020 research and innovation pr ogramme under grant agreement No. 777536. See http://eosc-hub.eu (2018)Apache License: author = https://www.apache.org/licenses/LICENSE-2.0 (2004)INDIGO Package Repo: http://repo.indigo-datacloud.eu/ (2017)INDIGO DockerHub: https://hub.docker.com/u/indigodatacloud/ https://hub.docker.com/u/indigodatacloud/ (2015)Indigo gitbook: https://indigo-dc.gitbooks.io/indigo-datacloud-releases https://indigo-dc.gitbooks.io/indigo-datacloud-releases (2017)Van Zundert, G.C., Bonvin, A.M.: Disvis: quantifying and visualizing the accessible interaction space of distance restrained biomolecular complexes. Bioinformatics 31(19), 3222–3224 (2015)Van Zundert, G.C., Bonvin, A.M.: Fast and sensitive rigid–body fitting into cryo–em density maps with powerfit. AIMS Biophys. 2(0273), 73–87 (2015

Working conditions and Work-Family Conflict in German hospital physicians: psychosocial and organisational predictors and consequences

<p>Abstract</p> <p>Background</p> <p>Germany currently experiences a situation of major physician attrition. The incompatibility between work and family has been discussed as one of the major reasons for the increasing departure of German physicians for non-clinical occupations or abroad. This study investigates predictors for one particular direction of Work-Family Conflict – namely work interfering with family conflict (WIF) – which are located within the psychosocial work environment or work organisation of hospital physicians. Furthermore, effects of WIF on the individual physicians' physical and mental health were examined. Analyses were performed with an emphasis on gender differences. Comparisons with the general German population were made.</p> <p>Methods</p> <p>Data were collected by questionnaires as part of a study on <it>Psychosocial work hazards and strains of German hospital physicians </it>during April–July 2005. Two hundred and ninety-six hospital physicians (response rate 38.9%) participated in the survey. The Copenhagen Psychosocial Questionnaire (COPSOQ), work interfering with family conflict scale (WIF), and hospital-specific single items on work organisation were used to assess WIF, its predictors, and consequences.</p> <p>Results</p> <p>German hospital physicians reported elevated levels of WIF (mean = 74) compared to the general German population (mean = 45, <it>p </it>< .01). No significant gender difference was found. Predictors for the WIF were lower age, high quantitative demands at work, elevated number of days at work despite own illness, and consequences of short-notice changes in the duty roster. Good sense of community at work was a protective factor. Compared to the general German population, we observed a significant higher level of quantitative work demands among hospital physicians (mean = 73 vs. mean = 57, <it>p </it>< .01). High values of WIF were significantly correlated to higher rates of personal burnout, behavioural and cognitive stress symptoms, and the intention to leave the job. In contrast, low levels of WIF predicted higher job satisfaction, better self-judged general health status, better work ability, and higher satisfaction with life in general. Compared to the German general population, physicians showed significantly higher levels of individual stress and quality of life as well as lower levels for well-being. This has to be judged as an alerting finding regarding the state of physicians' health.</p> <p>Conclusion</p> <p>In our study, work interfering with family conflict (WIF) as part of Work-Family Conflict (WFC) was highly prevalent among German hospital physicians. Factors of work organisation as well as factors of interpersonal relations at work were identified as significant predictors for WIF. Some of these predictors are accessible to alteration by improving work organisation in hospitals.</p

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.