Natural immune systems protect animals from dangerous foreign pathogens, including bacteria, viruses, parasites, and toxins. Their role in the body is analogous to that of computer security systems in computing. Although there are many differences between living organisms and computer systems, this article argues that the similarities are compelling and could point the way to improved computer security. Improvements can be achieved by designing computer immune systems that have some of the important properties illustrated by natural immune systems. These include multi-layered protection, highly distributed detection and memory systems, diversity of detection ability across individuals, inexact matching strategies, and sensitivity to most new foreign patterns. We first give an overview of how the immune system relates to computer security. We then illustrate these ideas with two examples.

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ABSTRACT: We report on recommendations from a National Institutes of Health Workshop on methods for evaluating the use of surrogate endpoints in clinical trials, which was attended by experts in biostatistics and clinical trials from a broad array of disease areas. Recent advances in biosciences and technology have increased the ability to understand, measure, and model biological mechanisms; appropriate application of these advances in clinical research settings requires collaboration of quantitative and laboratory scientists. Biomarkers, new examples of which arise rapidly from new technologies, are used frequently in such areas as early detection of disease and identification of patients most likely to benefit from new therapies. There is also scientific interest in exploring whether, and under what conditions, biomarkers may substitute for clinical endpoints of phase III trials, although workshop participants agreed that these considerations apply primarily to situations where trials using clinical endpoints are not feasible. Evaluating candidate biomarkers in the exploratory phases of drug development and investigating

The eradication of human immunodeficiency virus 1 (HIV-1) from infected persons is the ultimate goal of HIV therapeutic interventions. Great strides have been made in developing potent antiretroviral regimens that greatly suppress HIV-1 replication. Despite these therapeutic advances, major obstacles remain to eradicating HIV-1. Reservoirs of HIV-1 have been identified that represent major impediments to eradication. Conceptually, there are 2 types of sanctuaries for HIV-1, cellular and anatomical. Cellular sanctuaries may include latent CD4 + T cells containing integrated HIV-1 provirus; macrophages, which may express HIV-1 for prolonged periods; and follicular dendritic cells, which may hold infectious HIV-1 on their surfaces for indeterminate lengths of time. The key anatomical reservoir for HIV-1 appears to be the central nervous system. An understanding of the nature of HIV within these reservoirs is critical to devising strategies to hasten viral eradication. JAMA. 1998;280:67-71 DEVELOPING a means to eradicate

Treatment of a pathogenic disease process is interpreted as the optimal control of a dynamic system. Evolution of the disease is characterized by a non-linear, fourth-order ordinary differential equation that describes concentrations of pathogens, plasma cells, and antibodies, as well as a numerical indication of patient health. Without control, the dynamic model evidences sub-clinical or clinical decay, chronic stabilization, or unrestrained lethal growth of the pathogen, depending on the initial conditions for the infection. The dynamic equations are controlled by therapeutic agents that affect the rate of change of system variables. Control histories that minimize a quadratic cost function are generated by numerical optimization over a fixed time interval, given otherwise lethal initial conditions. Tradeoffs between cost function weighting of pathogens, organ health, and use of therapeutics are evaluated. Optimal control solutions that defeat the pathogen and preserve organ health are demonstrated for four different approaches to therapy. It is shown that control theory can point the way toward new protocols for treatment and remediation of human diseases. Copyright # 2002 John Wiley & Sons, Ltd. KEY WORDS: optimal control; biological modelling; bioinformatics; optimization

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this document included: Elaine Abrams, M.D. (Harlem Hospital Center, New York, NY); Arthur Ammann, M.D. (AmFAR, New York, NY); Martin Anderson, M.D., M.P.H. (University of California at Los Angeles, Los Angeles, CA); Lawrence Bernstein, M.D. (Albert Einstein College of Medicine, Bronx, NY); Carol Baker, M.D. (Baylor College of Medicine, Houston, TX); Michael Brady, M.D. (Columbus Children's Hospital, Columbus, OH); Kathleen Brooke (Family Representative); Carolyn Burr, Ph.D. (NPHRC, Newark, NJ); Sandra Burchett, M.D. (Children's Hospital, Boston, MA); Joseph Cervia, M.D. (Cornell Medical Center, New York, NY); Diana Clarke, Pharm.D. (Boston Medical Center, Boston, MA); Daniel Collado (Family Representative); Ellen Cooper, M.D. (Boston Medical Center, Boston, MA); Marilyn Crain, M.D., M.P.H. (University of Alabama at Birmingham, Birmingham, AL); Barry Dashefsky, M.D. (NPHRC and UMDNJ-New Jersey Medical School, Newark, NJ); Diane Donovan (Family Representative); Janet A. Englund, M.D. (Baylor College of Medicine, Houston, TX); Mary Glenn Fowler, M.D., M.P.H. (NIH, Rockville, MD); Lisa M. Frenkel, M.D. (University of Washington, Seattle, WA); Donna Futterman, M.D. (Montefiore Medical Center, New York, NY); Anne Gershon, M.D. (Columbia University, New York, NY); Samuel Grubman, M.D. (St. Vincent's Hospital and Medical Center of New York, New York, NY); Peter Havens, M.D. (Children's Hospital of Wisconsin, Milwaukee, WI); Karen Hench, M.S., (HRSA, Rockville, MD); Neal Hoffman, M.D. (Montefiore Medical Center, Bronx, NY); Walter Hughes, M.D. (St. Jude Children's Research Hospital, Memphis, TN); George Johnson, M.D. (Medical University of South Carolina, Charleston, SC); Rosemary Johnson (Family Representative); Michael Kaiser, M.D. (HRSA, Rockville, MD); Aaron Kaplan, M.D. (T...

.D. Food and Drug Administration Rockville, MD Mary Glenn Fowler, M.D. Centers for Disease Control and Prevention Atlanta, GA May 4, 2001 ii Federal Government Staff (Cont.): Eric Goosby, M.D. Office of HIV/AIDS Policy Washington, D.C. Karen Hench, R.N. Health Resources and Services Administration Rockville, MD Denise Jamieson, M.D. Centers for Disease Control and Prevention Atlanta, GA James McNamara, M.D. National Institutes of Health Rockville, MD Lynne Mofenson, M.D. (Executive Secretary) National Institutes of Health Rockville, MD Jose Morales, M.D. Health Resources and Services Administration Rockville, MD Deborah von Zinkernagel, R.N. Office of HIV/AIDS Policy Washington, D.C. D. Heather Watts, M.D. National Institutes of Health Rockville, MD Working Group Coordinating Center Staff: Carolyn Burr, Ed.D., R.N. National Pediatric and Family HIV Resource Center Newark, NJ Elaine Gross, R.N., M.S., C.N.S.-C. National Pediatric and F

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