Applications, tools and techniques on the road to exascale computing

This volume of the book series “Advances in Parallel Computing” contains the proceedings of ParCo2011, the 14th biennial ParCo Conference, held from 31 August to 3 September 2011, in Ghent, Belgium. In an era when physical limitations have slowed down advances in the performance of single processing units, and new scientific challenges require exascale speed, parallel processing has gained momentum as a key gateway to HPC (High Performance Computing). Historically, the ParCo conferences have focused on three main themes: Algorithms, Architectures (both hardware and software) and Applications. Nowadays, the scenery has changed from traditional multiprocessor topologies to heterogeneous manycores, incorporating standard CPUs, GPUs (Graphics Processing Units) and FPGAs (Field Programmable Gate Arrays). These platforms are, at a higher abstraction level, integrated in clusters, grids, and clouds. This is reflected in the papers presented at the conference and the contributions as included in these proceedings. An increasing number of new algorithms are optimized for heterogeneous platforms and performance tuning is targeting extreme scale computing. Heterogeneous platforms utilising the compute power and energy efficiency of GPGPUs (General Purpose GPUs) are clearly becoming mainstream HPC systems for a large number of applications in a wide spectrum of application areas. These systems excel in areas such as complex system simulation, real-time image processing and visualisation, etc. High performance computing accelerators may well become the cornerstone of exascale computing applications such as 3-D turbulent combustion flows, nuclear energy simulations, brain research, financial and geophysical modelling. The exploration of new architectures, programming tools and techniques was evidenced by the mini-symposia “Parallel Computing with FPGAs” and “Exascale Programming Models”. The need for exascale hardware and software was also stressed in the industrial session, with contributions from Cray and the European exascale software initiative. Our sincere appreciation goes to the keynote speakers who gave their perspectives on the impact of parallel computing today and the road to exascale computing tomorrow. Our heartfelt thanks go to the authors for their valuable scientific contributions and to the programme committee who reviewed the papers and provided constructive remarks. The international audience was inspired by the quality of the presentations. The attendance and interaction was high and the conference has been an agora where many fruitful ideas were exchanged and explored. We wish to express our sincere thanks to the organizers for the smooth operation of the conference. The University conference centre Het Pand offered an excellent environment for the conference as it allowed delegates to interact informally and easily. A special word of thanks is due to the management and support staff of Het Pand for their proficient and friendly support. The organizers managed to put together an extensive social programme. This included a reception at the medieval Town Hall of Ghent as well as a memorable conference dinner. These social events stimulated interaction amongst delegates and resulted in many new contacts being made. Finally we wish to thank all the many supporters who assisted in the organization and successful running of the event. Erik D'Hollander, Ghent University, Belgium Koen De Bosschere, Ghent University, Belgium Gerhard R. Joubert, TU Clausthal, Germany David Padua, University of Illinois, USA Frans Peters, Philips Research, Netherland

A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

ML, CD, IvL, GP, TM, SD, MS, APF, CT, DL, MAH, KL and SL: project grants from the Swedish Research Council, the Swedish Cancer Society and the Swedish Childhood Cancer Foundation. MHi and JC: Cancer Research UK (C8/A6613). MC, EP and WE: Wellcome Trust (073915). MN and BV: projects MEYS-NPS-LO1413 and GACR P206/12/G151. EMC, MP, MMS, ZF and PG: Norwegian Cancer Society (182735, 732200) and Helse Vest (911884, 911789). RB and SC: NIH (R01 CA95684), the Leukemia and Lymphoma Society and the Waxman Foundation. NW, AH, Ad’H: Cancer Research UK (C21383/A6950) and Engineering and Physical Sciences Research Council Doctoral Training Program. JL and YZ: Cancer Research UK (C240/A15751). MH and BW: SARomics Biostructures ABUY, KF: DDDP SciLife, Sweden. LJ, MHa, RS and A-LG: CBCS, Sweden. VP: SciLife fellowship. AT: Breast Cancer Research Scotland.The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.Publisher PDFPeer reviewe

EU-Brazil Relations at the World Trade Organization: Dispute Settlement as Leverage

This paper addresses how Brazil’s use of the WTO dispute settlement vis-à-vis the EU has an impact on trade relations between both parties. After describing their economic relationship, it is demonstrated that Brazil and the EU are not only successful and avid users of the dispute settlement system, but are also striving to strengthen its judicialization. Together with indirect economic advantages and agenda-setting capacities, the judicialization of the WTO dispute settlement system can be considered factors by which Brazil relatively strengthened its position vis-à-vis the EU. However, the final section of the paper demonstrates how tensions within Mercosur, the rise of mega-regionalism and the prioritization of the EU’s negotiation capacity towards the U.S. and Japan, undermine Brazil’s position in trade relations with the EU.nrpages: 20status: publishe

Report on the analysis and critical assessment of EU engagement in UN bodies

This report presents the outcome of the analysis and critical assessment of EU human rights engagement in UN bodies. The EU has committed itself in the Treaty on the European Union to ‘promote multilateral solutions to common problems, in particular in the framework of the United Nations.’ In light of this provision, and taking into account the considerable challenges the EU-UN cooperation encounters, the present report aims at four goals. Firstly, to map the long-standing and multifaceted engagement of the EU within and towards UN human rights bodies. Secondly, to critically assess the EU’s engagement in the UN from the perspective of both its policy and institutions. Thirdly, to identify specific and structural flaws in the EU’s approach to human rights at the UN. Fourthly, to find creative ways of enhancing the EU’s position, role, inclusion in and impact upon these UN bodies. The deliverable consists of seven chapters. The first chapter presents the aims of the report and the methodology of the research. It also explains the key concepts of the deliverable, such as coherence, leadership or mutual influence between the EU and the UN. The second chapter explores two of the guiding principles of the EU’s external policy: human rights and multilateralism. In particular, it contains an analysis of the Union’s commitment to ‘effective multilateralism’ and consistency of specific human rights priorities throughout the EU legislation and other documents. The third chapter presents the institutional framework of the EU-UN relations. As both, the EU and the UN, share a common trait – a high complexity of their organisational structure, chapter III begins with a detailed mapping of both organisations. It also explains the role of different stakeholders in the EU-UN cooperation. This chapter also tackles the relationships between stakeholders and the coordination of the EU’s position at the UN. The status of the EU in the UN is also explored from the point of view of the legal framework of both organisations. The fourth chapter presents the processes and dynamics behind the formulation of EU human rights aims, objectives and priorities at the UN. It indicates the critical factors, relevant actors and their roles as well as the overall characteristics of the process. The chapter also provides a detailed analysis of the EU’s specific goals and objectives at the UN as well as their consistency. The report focuses on the Union’s priorities with regard to (i) thematic human rights issues, (ii) its country-specific priorities, and (iii) its aims and objectives relating to the institutional architecture of the UN. The fifth chapter concerns the tools and methods deployed by the EU at the UN. Particular attention has been paid to the issue of the EU’s resolution initiatives in UN human rights fora: the UNGA Third Committee and the HRC. The analysis focuses on resolution initiatives tabled by the Union, but also tackles the national initiatives of the EU Member States and the co-sponsoring of resolutions by the EU/Member States. It also explores the EU’s involvement in the Universal Periodic Review (UPR) process. Taking into account that the EU does not formally participate in the UPR, the involvement of its Member States is analysed, also from the point of view of realisation of EU human rights priorities. This section also explains the notion of light-coordination. Finally, the fifth chapter explores the EU’s financial contribution to UN human rights activities, in particular to the Office of the High Commissioner of Human Rights. The deliverable is supplemented by four case studies included in chapter six of the deliverable. They are related to EU’s engagement in specific thematic topics at the UN covering the areas of: economic, social and cultural rights, human rights defenders, the right to development and counterterrorism. The final chapter presents the conclusions of the research. Due to the comprehensive nature of the analysis of the various dimensions of EU-UN interaction, the report seeks not only to advance the existing knowledge on the topic, but also to create a broad base for future research. In particular, the findings of this study will constitute the background for next deliverables of this work package on the Union’s engagement with regional multilateral organisations.Fostering Human Rights among European Policies (FRAME); Large-Scale FP7 Collaborative Project GA No. 320000; Work Package No. 5 – Deliverable No. 5.1nrpages: 259status: publishe

Effect of plant milk consumption on childhood growth: protocol for a systematic review

Introduction There has been considerable debate about whether plant milks can support the nutritional requirements of growing children. The proposed systematic review aims to assess the evidence on the relationship between plant milk consumption and growth and nutritional status in childhood.Methods and analysis Ovid MEDLINE ALL (1946–present), Ovid EMBASE Classic (1947–present), CINAHL Complete (Cumulative Index to Nursing and Allied Health Literature), Scopus, the Cochrane Library and grey literature will be searched comprehensively (from 2000 to present; English language) to find studies that describe the association between plant milk consumption and growth or nutrition in children 1–18 years of age. Two reviewers will identify eligible articles, extract data and assess the risk of bias in individual studies. If a meta-analyses is not conducted, the evidence will be synthesised narratively and the overall certainty of evidence will be rated using the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and dissemination Ethical approval is not required for this study since no data will be collected. Results of the systematic review will be published in a peer-reviewed journal. Findings from this study may be useful in informing future evidence-based recommendations about plant milk consumption in children.PROSPERO registration number CRD42022367269

Human Dihydroorotate Dehydrogenase in complex with novel inhibitor (PDB entry 6ET4)

atomic coordinates and structure factor