High resolution >40 keV x-ray radiography using an edge-on micro-flag backlighter at NIF-ARC.

Radiography of low-contrast features in high-density materials evolving on a nanosecond timescale requires a bright photon source in the tens of keV range with high temporal and spatial resolution. One application for sources in this category is the study of dynamic material strength in samples compressed to Mbar pressures at the National Ignition Facility, high-resolution measurements of plastic deformation under conditions relevant to meteor impacts, geophysics, armor development, and inertial confinement fusion. We present radiographic data and the modulation transfer function (MTF) analysis of a multi-component test object probed at ∼100 keV effective backlighter energy using a 5 µm-thin dysprosium foil driven by the NIF Advanced Radiographic Capability (ARC) short-pulse laser (∼2 kJ, 10 ps). The thin edge of the foil acts as a bright line-projection source of hard x rays, which images the test object at 13.2× magnification into a filtered and shielded image plate detector stack. The system demonstrates a superior contrast of shallow (5 µm amplitude) sinusoidal ripples on gold samples up to 90 µm thick as well as enhanced spatial and temporal resolution using only a small fraction of the laser energy compared to an existing long-pulse-driven backlighter used routinely at the NIF for dynamic strength experiments.

Extreme Hardening of Pb at High Pressure and Strain Rate.

We study the high-pressure strength of Pb and Pb-4wt%Sb at the National Ignition Facility. We measure Rayleigh-Taylor growth of preformed ripples ramp compressed to ∼400 GPa peak pressure, among the highest-pressure strength measurements ever reported on any platform. We find agreement with 2D simulations using the Improved Steinberg-Guinan strength model for body-centered-cubic Pb; the Pb-4wt%Sb alloy behaves similarly within the error bars. The combination of high-rate, pressure-induced hardening and polymorphism yield an average inferred flow stress of ∼3.8 GPa at high pressure, a ∼250-fold increase, changing Pb from soft to extremely strong.

Retroviral antibody binding of the MHC class II molecule: a biochemical influence on CD4 T cell differentiation in HIV infection?

Retroviral antibody capable of binding to the major histocompatibility complex (MHC) Class II molecule has been documented in human immunodeficiency virus-1 (HIV-1)-infected patients. Interactions between the MHC Class II receptor and the T-cell receptor (TCR) are central to the immune response. Importantly, retroviral antibody possesses a much higher binding affinity for the MHC Class II receptor, when compared to the TCR. Experiments have manipulated a number of factors related to antigen-presenting cell (APC) interaction with differentiating T-cells. These studies have observed the effects of lowering antigen dose and reducing ligand density on precursor Th (T helper) cell differentiation. Studies have also examined the effect of downregulated MHC Class II receptors and co-stimulatory molecules on APC-Th cell interaction. In addition, the sequestration of antigens away from the Class II processing pathway has been studied. These investigations reveal a general trend that can determine whether a naive CD4 T-cell becomes a Th1 or Th2-like cell. If the experimental manipulation weakens the APC-Th cell interaction, a weak ligating TCR signal results. Consequently, a weak ligating TCR signal can influence precursor Th cells to become Th2-like cells. Retroviral antibody binding of MHC Class II receptors may mimic a number of experimental conditions responsible for creating a weak ligating TCR signal.

Evolutionary stable strategy: a test for theories of retroviral pathology which are based upon the concept of molecular mimicry.

The genetic makeup of animal and plant populations is determined by established principles and concepts. Ecology and evolution provide a basic theoretical framework for understanding how genetic changes occur in populations. Whether these rules can be applied to host retroviral populations is unknown. Individuals infected with the human immunodeficiency virus (HIV) contain within their bodies a viral population. This population is known as a viral quasispecies. Located in the transmembrane protein of HIV-1 is the viral sequence Gly-Thr-Asp-Arg-Val. Previous immunological studies have shown that viral antibody is produced in response to this five-amino-acid sequence. Antibody to this viral sequence also crossreacts and binds to a related peptide sequence found on certain immune cells. This related sequence, Gly-Thr-Glu-Arg-Val, is found on immune cells bearing a structure known as the major histocompatibility complex (MHC). The viral transmembrane sequence, Gly-Thr-Asp-Arg-Val, can be substituted with alanine residues utilizing site-directed mutagenesis. This creates a viral clone devoid of the genetic similarity with the MHC. Chimpanzees progressing to AIDS contain both sequences of interest. Suppression of the chimpanzee quasispecies utilizing anti-retroviral drugs is proposed. This action serves to suppress the presence of the viruses containing the sequence Gly-Thr-Asp-Arg-Val. When viral load has been reduced significantly, a drug resistant, alanine altered clone is to be introduced in large numbers. The concept of evolutionary stable strategy predicts that a viable HIV clone with alanine residues can genetically dominate the viral population. Immune system recognition of the alanine sequence is likely to result in renewed antibody production. Antibodies to the alanine containing viral sequence should not recognize or bind to the MHC. Immunological parameters can then be measured to determine the physiological impact of eliminating a sequence responsible for molecular mimicry between virus and host.

One explanation of Nef gene behavior.

The Nef (negative factor) gene of primate retroviruses may serve an important evolutionary function. Selection pressures in the natural world, may at times, demand that retroviral infection not cause disease in a newly entered host species. Genetic alterations in the Nef gene may function to permit retroviral speciation by lowering retroviral replication rate. Slow viral replication may allow small numbers of the newly infected host species to avoid the effects of retroviral pathology.

Can site-directed mutagenesis eliminate autoimmunity arising from molecular mimicry?

One proposed mechanism of pathogenic retroviral infection involves autoimmunity. Molecular mimicry may occur between viral and host proteins which share sequence homologies. Immune processing of antigenic peptides can result in the generation of cross-reactive antibodies capable of binding to host tissues. Thus, it appears the immune system can inadvertently initiate an attack upon the host due to genetic similarities between non-self and self. Site-directed mutagenesis is a tool of molecular biology often utilized to induce genetic changes in a microbe of interest. Since retroviral etiology may possess an autoimmune component, it seems plausible to utilize site-directed mutagenesis to genetically shape the retroviral genome. Retroviruses possess a DNA intermediate in their lifecycle, allowing the problem of retroviral infection to be addressed as a genetic disorder of the host. Detrimental autoimmune responses associated with retroviral pathology might be ameliorated by shaping the genetic source of their existence.

Can evolutionary principles help resolve the acquired immune deficiency syndrome crisis?

The population of retroviruses inside each infected host can quickly adapt its genes in response to survival threats. For this reason, therapeutics attempting to eliminate or inhibit the human immunodeficiency virus have been unsuccessful. However, it may be possible to apply evolutionary principles to the problem of human immunodeficiency virus infection/acquired immune deficiency syndrome. The rapid evolution capabilities of this pathogen might assist researchers in evolving human immunodeficiency virus toward the goal of virus-host coexistence. In this relationship, infecting viruses do not harm their host. Two different examples illustrate the theoretical application of evolutionary principles to this problem. First, by viewing the virus as a new gene of the immune system, it is possible to evolve this gene toward the goal of improving immune function. Second, the retroviral population of each host is maladapted for long-term survival. Retroviral genes could be evolved with respect to continued existence in the host.

Iron supplementation and running performance in female cross-country runners.

The purpose of this study was to determine the effects of two weeks of high dosage iron supplementation on various blood iron indices and metabolic parameters in non-anemic, iron-depleted competitive female cross-country runners. The subjects were highly trained members of the Colorado State University cross-country team and were completing 40 to 50 miles of training weekly. A pretest, post-test single-blind crossover design was employed. Upon collection of baseline exercise blood and metabolic data, five subjects were randomly assigned to iron supplementation (650 mg ferrous sulfate; 130 mg elemental iron) and five subjects to placebo treatment. At two weeks the treatments were reversed. Exercise blood and metabolic data were collected at two-week intervals. Dietary iron intake was assessed using a three-day dietary survey. Dietary analysis revealed deficiencies in vitamin B-6, iron, magnesium, and zinc according to USRDA standards. Baseline blood samples revealed no deficiencies in iron storage or transport proteins. Two weeks of iron supplementation resulted in no significant increases in blood iron indices. Metabolic parameters related to running performance were also unchanged after iron supplementation. High dosage, short-term iron supplementation appears to have no effect on blood or metabolic parameters in iron-depleted but non-anemic female cross-country runners.