22 research outputs found
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Improved utilization and responsiveness with gang scheduling
Most commercial multicomputers use space-slicing schemes in which each scheduling decision has an unknown impact on the future: should a job be scheduled, risking that it will block other larger jobs later, or should the processors be left idle for now in anticipation of future arrivals? This dilemma is solved by using gang scheduling, because then the impact of each decision is limited to its time slice, and future arrivals can be accommodated in other time slices. This added flexibility is shown to improve overall system utilization and responsiveness. Empirical evidence from using gang scheduling on a Cray T3D installed at Lawrence Livermore National Lab corroborates these results, and shows conclusively that gang scheduling can be very effective with current technology. 29 refs., 10 figs., 6 tabs
Designing a broad-spectrum integrative approach for cancer prevention and treatment
Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered
HBV X protein: Elucidating a role in oncogenesis
Chronic HBV infection is associated with the development of hepatocellular carcinoma (HCC). HBV contributes to tumorigenesis by encoding hepatitis B x antigen (HBxAg), which is a trans-regulatory protein that appears to contribute to HCC by altering patterns of host gene expression. In this review, recent data is presented that outlines some of the putative mechanisms whereby HBxA9 contributes to HCC. With the development of animal models of HBxAg-mediated HCC, the relevance and temporal order of putative steps in this process can now be dissected to elucidate what is rate limiting and when. This will have a profound impact on the design of novel and specific therapeutics for HCC. © 2008 Future Medicine Ltd