The Argonne Leadership Computing Facility 2010 annual report.

Researchers found more ways than ever to conduct transformative science at the Argonne Leadership Computing Facility (ALCF) in 2010. Both familiar initiatives and innovative new programs at the ALCF are now serving a growing, global user community with a wide range of computing needs. The Department of Energy's (DOE) INCITE Program remained vital in providing scientists with major allocations of leadership-class computing resources at the ALCF. For calendar year 2011, 35 projects were awarded 732 million supercomputer processor-hours for computationally intensive, large-scale research projects with the potential to significantly advance key areas in science and engineering. Argonne also continued to provide Director's Discretionary allocations - 'start up' awards - for potential future INCITE projects. And DOE's new ASCR Leadership Computing (ALCC) Program allocated resources to 10 ALCF projects, with an emphasis on high-risk, high-payoff simulations directly related to the Department's energy mission, national emergencies, or for broadening the research community capable of using leadership computing resources. While delivering more science today, we've also been laying a solid foundation for high performance computing in the future. After a successful DOE Lehman review, a contract was signed to deliver Mira, the next-generation Blue Gene/Q system, to the ALCF in 2012. The ALCF is working with the 16 projects that were selected for the Early Science Program (ESP) to enable them to be productive as soon as Mira is operational. Preproduction access to Mira will enable ESP projects to adapt their codes to its architecture and collaborate with ALCF staff in shaking down the new system. We expect the 10-petaflops system to stoke economic growth and improve U.S. competitiveness in key areas such as advancing clean energy and addressing global climate change. Ultimately, we envision Mira as a stepping-stone to exascale-class computers that will be faster than petascale-class computers by a factor of a thousand. Pete Beckman, who served as the ALCF's Director for the past few years, has been named director of the newly created Exascale Technology and Computing Institute (ETCi). The institute will focus on developing exascale computing to extend scientific discovery and solve critical science and engineering problems. Just as Pete's leadership propelled the ALCF to great success, we know that that ETCi will benefit immensely from his expertise and experience. Without question, the future of supercomputing is certainly in good hands. I would like to thank Pete for all his effort over the past two years, during which he oversaw the establishing of ALCF2, the deployment of the Magellan project, increases in utilization, availability, and number of projects using ALCF1. He managed the rapid growth of ALCF staff and made the facility what it is today. All the staff and users are better for Pete's efforts

Accelerating scientific discovery : 2007 annual report.

As a gateway for scientific discovery, the Argonne Leadership Computing Facility (ALCF) works hand in hand with the world's best computational scientists to advance research in a diverse span of scientific domains, ranging from chemistry, applied mathematics, and materials science to engineering physics and life sciences. Sponsored by the U.S. Department of Energy's (DOE) Office of Science, researchers are using the IBM Blue Gene/L supercomputer at the ALCF to study and explore key scientific problems that underlie important challenges facing our society. For instance, a research team at the University of California-San Diego/ SDSC is studying the molecular basis of Parkinson's disease. The researchers plan to use the knowledge they gain to discover new drugs to treat the disease and to identify risk factors for other diseases that are equally prevalent. Likewise, scientists from Pratt & Whitney are using the Blue Gene to understand the complex processes within aircraft engines. Expanding our understanding of jet engine combustors is the secret to improved fuel efficiency and reduced emissions. Lessons learned from the scientific simulations of jet engine combustors have already led Pratt & Whitney to newer designs with unprecedented reductions in emissions, noise, and cost of ownership. ALCF staff members provide in-depth expertise and assistance to those using the Blue Gene/L and optimizing user applications. Both the Catalyst and Applications Performance Engineering and Data Analytics (APEDA) teams support the users projects. In addition to working with scientists running experiments on the Blue Gene/L, we have become a nexus for the broader global community. In partnership with the Mathematics and Computer Science Division at Argonne National Laboratory, we have created an environment where the world's most challenging computational science problems can be addressed. Our expertise in high-end scientific computing enables us to provide guidance for applications that are transitioning to petascale as well as to produce software that facilitates their development, such as the MPICH library, which provides a portable and efficient implementation of the MPI standard--the prevalent programming model for large-scale scientific applications--and the PETSc toolkit that provides a programming paradigm that eases the development of many scientific applications on high-end computers

Argonne Leadership Computing Facility 2011 annual report : Shaping future supercomputing.

The ALCF's Early Science Program aims to prepare key applications for the architecture and scale of Mira and to solidify libraries and infrastructure that will pave the way for other future production applications. Two billion core-hours have been allocated to 16 Early Science projects on Mira. The projects, in addition to promising delivery of exciting new science, are all based on state-of-the-art, petascale, parallel applications. The project teams, in collaboration with ALCF staff and IBM, have undertaken intensive efforts to adapt their software to take advantage of Mira's Blue Gene/Q architecture, which, in a number of ways, is a precursor to future high-performance-computing architecture. The Argonne Leadership Computing Facility (ALCF) enables transformative science that solves some of the most difficult challenges in biology, chemistry, energy, climate, materials, physics, and other scientific realms. Users partnering with ALCF staff have reached research milestones previously unattainable, due to the ALCF's world-class supercomputing resources and expertise in computation science. In 2011, the ALCF's commitment to providing outstanding science and leadership-class resources was honored with several prestigious awards. Research on multiscale brain blood flow simulations was named a Gordon Bell Prize finalist. Intrepid, the ALCF's BG/P system, ranked No. 1 on the Graph 500 list for the second consecutive year. The next-generation BG/Q prototype again topped the Green500 list. Skilled experts at the ALCF enable researchers to conduct breakthrough science on the Blue Gene system in key ways. The Catalyst Team matches project PIs with experienced computational scientists to maximize and accelerate research in their specific scientific domains. The Performance Engineering Team facilitates the effective use of applications on the Blue Gene system by assessing and improving the algorithms used by applications and the techniques used to implement those algorithms. The Data Analytics and Visualization Team lends expertise in tools and methods for high-performance, post-processing of large datasets, interactive data exploration, batch visualization, and production visualization. The Operations Team ensures that system hardware and software work reliably and optimally; system tools are matched to the unique system architectures and scale of ALCF resources; the entire system software stack works smoothly together; and I/O performance issues, bug fixes, and requests for system software are addressed. The User Services and Outreach Team offers frontline services and support to existing and potential ALCF users. The team also provides marketing and outreach to users, DOE, and the broader community

Ethics and social responsibility in practice: interpreters and translators engaging with and beyond the professions

Interpreting and translation are unregulated activities in most countries, yet interpreters and translators perform challenging work in sensitive domains, such as the law, medicine and social work. Other professionals working in these sectors must complete formal ethics training to qualify, then subscribe to Codes of Practice or Ethics. When they face ethical challenges in their work, they can access ongoing support. They must undertake regular refresher training in ethics. Interpreters and translators rarely have access to this sort of ethical infrastructure. This places the onus on interpreters and translators to reflect on ethical aspects of their practice, for reasons related to both professional performance and social responsibility. This contribution presents original UK-based research with one type of professional ‘clients’ who rely on interpreters and translators, social workers and social work students prior to their first work experience placement. Findings suggest that insufficient attention has been paid to such professional clients and that ethical aspects of professional communication can be compromised as a result. By framing ethics training and ongoing support in terms of social responsibility, we point to some ways in which the different professional groups might communicate and work more effectively with one another and with service users

Leadership and the Australian Greens

This paper examines the inherent tension between a Green political party’s genesis and official ideology and the conventional forms and practices of party leadership enacted in the vast bulk of other parties, regardless of their place on the ideological spectrum. A rich picture is painted of this ongoing struggle through a case study of the Australian Greens with vivid descriptions presented on organisational leadership issues by Australian state and federal Green members of parliaments. What emerges from the data is the Australian Green MPs’ conundrum in retaining an egalitarian and participatory democracy ethos while seeking to expand their existing frame of leadership to being both more pragmatic and oriented towards active involvement in government

A-RAF Kinase Functions in ARF6 Regulated Endocytic Membrane Traffic

BACKGROUND: RAF kinases direct ERK MAPK signaling to distinct subcellular compartments in response to growth factor stimulation. METHODOLOGY/PRINCIPAL FINDINGS: Of the three mammalian isoforms A-RAF is special in that one of its two lipid binding domains mediates a unique pattern of membrane localization. Specific membrane binding is retained by an N-terminal fragment (AR149) that corresponds to a naturally occurring splice variant termed DA-RAF2. AR149 colocalizes with ARF6 on tubular endosomes and has a dominant negative effect on endocytic trafficking. Moreover actin polymerization of yeast and mammalian cells is abolished. AR149/DA-RAF2 does not affect the internalization step of endocytosis, but trafficking to the recycling compartment. CONCLUSIONS/SIGNIFICANCE: A-RAF induced ERK activation is required for this step by activating ARF6, as A-RAF depletion or inhibition of the A-RAF controlled MEK-ERK cascade blocks recycling. These data led to a new model for A-RAF function in endocytic trafficking

Maternal hormone levels among populations at high and low risk of testicular germ cell cancer

Ethnic differences in maternal oestrogen levels have been suggested as explaining the significantly higher risk of testicular germ cell tumours (TGCT) of white men than black men in the United States. We therefore examined levels of maternal oestrogens, as well as testosterone and alphafetoprotein (AFP), in 150 black and 150 white mothers in the Collaborative Perinatal Project. Serum levels of estradiol (total, free and bioavailable), estriol, testosterone (total, free and bioavailable), sex hormone binding globulin (SHBG), and AFP were examined during first and third trimesters. We found that the black mothers, rather than the white mothers, had significantly higher estradiol levels in first trimester (P=0.05). Black mothers also had significantly higher levels of all testosterone (P<0.001) and AFP (P<0.001) in both trimesters. In addition, the ratios of sex hormones (estradiol/testosterone) were significantly lower among black mothers. These findings provide little support to the oestrogen hypothesis, but are consistent with higher levels of testosterones and/or AFP being associated with reduced risk of TGCT; alternatively, lower oestrogen/androgen ratios may be associated with reduced risk

Genetic Disruption of Both Tryptophan Hydroxylase Genes Dramatically Reduces Serotonin and Affects Behavior in Models Sensitive to Antidepressants

The neurotransmitter serotonin (5-HT) plays an important role in both the peripheral and central nervous systems. The biosynthesis of serotonin is regulated by two rate-limiting enzymes, tryptophan hydroxylase-1 and -2 (TPH1 and TPH2). We used a gene-targeting approach to generate mice with selective and complete elimination of the two known TPH isoforms. This resulted in dramatically reduced central 5-HT levels in Tph2 knockout (TPH2KO) and Tph1/Tph2 double knockout (DKO) mice; and substantially reduced peripheral 5-HT levels in DKO, but not TPH2KO mice. Therefore, differential expression of the two isoforms of TPH was reflected in corresponding depletion of 5-HT content in the brain and periphery. Surprisingly, despite the prominent and evolutionarily ancient role that 5-HT plays in both vertebrate and invertebrate physiology, none of these mutations resulted in an overt phenotype. TPH2KO and DKO mice were viable and normal in appearance. Behavioral alterations in assays with predictive validity for antidepressants were among the very few phenotypes uncovered. These behavioral changes were subtle in the TPH2KO mice; they were enhanced in the DKO mice. Herein, we confirm findings from prior descriptions of TPH1 knockout mice and present the first reported phenotypic evaluations of Tph2 and Tph1/Tph2 knockout mice. The behavioral effects observed in the TPH2 KO and DKO mice strongly confirm the role of 5-HT and its synthetic enzymes in the etiology and treatment of affective disorders