Book Review of Clovis E. Semmes, Racism, Health, and Post-Industrialism: A Theory of African-American Health

Review of Clovis E. Semmes, Racism, Health, and Post-Industrialism: A Theory of African-American Health (Praeger Publishers 1996). About the author, acknowledgements, index, introduction, selected bibliography. LC-95-34440; ISBN 0-275-95428-5 [178 pp. Cloth $59.95, paper$18.95. 88 Post Road West, Westport CT 06881.

Comparison of continuous and discontinuous collisional bumpers: Dimensionally scaled impact experiments into single wire meshes

An experimental inquiry into the utility of discontinuous bumpers was conducted to investigate the collisional outcomes of impacts into single grid-like targets and to compare the results with more traditional bumper designs that employ continuous sheet stock. We performed some 35 experiments using 6.3 and 3.2 mm diameter spherical soda-lime glass projectiles at low velocities (less than 2.5 km/s) and 13 at velocities between 5 and 6 km/s, using 3.2 mm spheres only. The thrust of the experiments related to the characterization of collisional fragments as a function of target thickness or areal shield mass of both bumper designs. The primary product of these experiments was witness plates that record the resulting population of collisional fragments. Substantial interpretive and predictive insights into bumper performance were obtained. All qualitative observations (on the witness plates) and detailed measurements of displaced masses seem simply and consistently related only to bumper mass available for interaction with the impactor. This renders the grid bumper into the superior shield design. These findings present evidence that discontinuous bumpers are a viable concept for collisional shields, possibly superior to continuous geometries

Impact experiments into multiple-mesh targets: Concept development of a lightweight collisional bumper

The utility of multiple-mesh targets as potential lightweight shields to protect spacecraft in low-Earth orbit against collisional damage is explored. Earlier studies revealed that single meshes comminute hypervelocity impactors with efficiencies comparable to contiguous targets. Multiple interaction of projectile fragments with any number of meshes should lead to increased comminution, deceleration, and dispersion of the projectile, such that all debris exiting the mesh stack possesses low specific energies (ergs/sq cm) that would readily be tolerated by many flight systems. The study is conceptually exploring the sensitivity of major variables such as impact velocity, the specific areal mass (g/sq cm) of the total mesh stack (SM), and the separation distance (S) between individual meshes. Most experiments employed five or ten meshes with total SM typically less than 0.5 the specific mass of the impactor, and silicate glass impactors rather than metal projectiles. While projectile comminution increases with increasing impact velocity due to progressively higher shock stresses, encounters with multiple-meshes at low velocity (1-2 km/s) already lead to significant disruption of the glass impactors, with the resulting fragments being additionally decelerated and dispersed by subsequent meshes, and, unlike most contiguous single-plate bumpers, leading to respectable performance at low velocity. Total specific bumper mass must be the subject of careful trade-off studies; relatively massive bumpers will generate too much debris being dislodged from the bumper itself, while exceptionally lightweight designs will not cause sufficient comminution, deceleration, or dispersion of the impactor. Separation distance was found to be a crucial design parameter, as it controls the dispersion of the fragment cloud. Substantial mass savings could result if maximum separation distances were employed. The total mass of debris dislodged by multiple-mesh stacks is modestly smaller than that of single, contiguous-membrane shields. The cumulative surface area of all penetration holes in multiple mesh stacks is an order of magnitude smaller than that in analog multiple-foil shields, suggesting good long-term performance of the mesh designs. Due to different experimental conditions, direct and quantitative comparison with other lightweight shields is not possible at present

Cratering and penetration experiments in teflon targets at velocities from 1 to 7 km/s

Approximately 20 sq m of protective thermal blankets, largely composed of Teflon, were retrieved from the Long Duration Exposure Facility after the spacecraft spent approximately 5.7 years in space. Examination of these blankets revealed that they contained thousands of hypervelocity impact features ranging from micron-sized craters to penetration holes several millimeters in diameter. We conducted impact experiments to reproduce such features and to understand the relationships between projectile size and the resulting crater or penetration hole diameter over a wide range of impact velocities. Such relationships are needed to derive the size and mass frequency distribution and flux of natural and man-made particles in low-earth orbit. Powder propellant and light-gas guns were used to launch soda-lime glass spheres into pure Teflon targets at velocities ranging from 1 to 7 km/s. Target thickness varied over more than three orders of magnitude from finite halfspace targets to very thin films. Cratering and penetration of massive Teflon targets is dominated by brittle failure and the development of extensive spall zones at the target's front and, if penetrated, the target's rear side. Mass removal by spallation at the back side of Teflon targets may be so severe that the absolute penetration hole diameter can become larger than that of a standard crater. The crater diameter in infinite halfspace Teflon targets increases, at otherwise constant impact conditions, with encounter velocity by a factor of V (exp 0.44). In contrast, the penetration hole size in very thin foils is essentially unaffected by impact velocity. Penetrations at target thicknesses intermediate to these extremes will scale with variable exponents of V. Our experimental matrix is sufficiently systematic and complete, up to 7 km/s, to make reasonable recommendations for velocity-scaling of Teflon craters and penetrations. We specifically suggest that cratering behavior and associated equations apply to all impacts in which the shock-pulse duration of the projectile is shorter than that assigned a unique projectile size, provided an impact velocity is known or assumed. This calibration seems superior to the traditional ballistic-limit approach

Penetration experiments in aluminum 1100 targets using soda-lime glass projectiles

The cratering and penetration behavior of annealed aluminum 1100 targets, with thickness varied from several centimeters to ultra-thin foils less than 1 micrometer thick, were experimentally investigated using 3.2 mm diameter spherical soda-lime glass projectiles at velocities from 1 to 7 km/s. The objective was to establish quantitative, dimensional relationships between initial impact conditions (impact velocity, projectile diameter, and target thickness) and the diameter of the resulting crater or penetration hole. Such dimensional relationships and calibration experiments are needed to extract the diameters and fluxes of hypervelocity particles from space-exposed surfaces and to predict the performance of certain collisional shields. The cratering behavior of aluminum 1100 is fairly well predicted. However, crater depth is modestly deeper for our silicate impactors than the canonical value based on aluminum projectiles and aluminum 6061-T6 targets. The ballistic-limit thickness was also different. These differences attest to the great sensitivity of detailed crater geometry and penetration behavior on the physical properties of both the target and impactor. Each penetration experiment was equipped with a witness plate to monitor the nature of the debris plume emanating from the rear of the target. This plume consists of both projectile fragments and target debris. Both penetration hole and witness-plate spray patterns systematically evolve in response to projectile diameter/target thickness. The relative dimensions of the projectile and target totally dominate the experimental products documented in this report; impact velocity is an important contributor as well to the evolution of penetration holes, but is of subordinate significance for the witness-plate spray patterns

STAT4 deficiency reduces obesity-induced insulin resistance and adipose tissue inflammation

Signal transducer and activator of transcription (STAT) 4 is one of the seven members of the STAT family. STAT4 has a prominent role in mediating interleukin-12-induced T-helper cell type 1 lineage differentiation. T cells are key players in the maintenance of adipose tissue (AT) inflammation. The role of STAT4 in obesity and AT inflammation is unknown. We sought to determine the role of STAT4 in AT inflammation in obesity-induced insulin resistance. We studied STAT4-null mice on the C57Bl6/J background. We have found that STAT4(-/-)C57Bl6/J mice develop high-fat diet-induced obesity (DIO) similar to wild-type controls, but that they have significantly improved insulin sensitivity and better glucose tolerance. Using flow cytometry and real-time PCR, we show that STAT4(-/-) mice with DIO produce significantly reduced numbers of inflammatory cytokines and chemokines in adipocytes, have reduced numbers of CD8(+) cells, and display increased alternative (M2) macrophage polarization. CD8(+) cells, but not CD4(+) cells, from STAT4(-/-) mice displayed reduced in vitro migration. Also, we found that adipocyte inflammation is reduced and insulin signaling is improved in STAT4(-/-) mice with DIO. We have identified STAT4 as a key contributor to insulin resistance and AT inflammation in DIO. Targeting STAT4 activation could be a novel approach to reducing AT inflammation and insulin resistance in obesity

Cultivating Agricultural Literacy: Challenge for the Liberal Arts

A review and analysis of 11 pacesetting experiments funded by the W. K. Kellogg Foundation to generate greater awareness among liberal arts students and faculty about the role and importance ofthe agriculture enterprise to the nation

A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A

Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Δ32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Δ32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this populatio

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival