663 research outputs found

    Results of the 1997 Illinois Deer Hunter Survey

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    Administrative ReportReport issued on: July 17, 200

    Modal Control of an Unstable Periodic Orbit

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    We apply Floquet theory to the problem of designing a control system for a satellite in an unstable periodic orbit. Expansion about a periodic orbit produces a time periodic linear system, which is augmented by a time periodic control term. We show that this can be done such that a) the application of control produces only inertial accelerations, b) positive real Poincare exponents are shifted into the left half-plane, and c) the shift of the exponent is linear with control gain. We apply these developments to an unstable orbit near the Earth-Moon L3 point perturbed by the Sun. Finally, we show that the control theory can be extended to include first order perturbations about the periodic orbit without increase in control cost

    The determination of photoneutron thresholds

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    Inspection Requirements for Adhesive Bonded Primary Structures

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    This paper is concerned with a program that\u27s being sponsored by the Air Force for the purpose of building an adhesive bonded structure. A discussion will be given on some of the problems that we are currently trying to address; what we are doing to solve these problems; and some of the road map programs that will support the Primary Adhesive Bonded Structure Techno logy (PABST) program. This program is under contract with t he McDonald-Douglas Corp., Long Beach. The objective of this program is to demonstrate and validate t hat by the use of adhesive bonding as the primary joining method that a structure can be fabricated that will be cheaper, lighter i n weight, and reliable. The approach is to review and analyze several design configurations and select a single design for fabrication. To support this decision testing will be accomplished on actual test components representative of the design selected, in addition to extensive coupon testing . After fabrication the structure will be subjected to several life cycle test s at the Air Force Flight Dynamics Laboratory, Wright-Patterson Air Force Base, Ohi

    Peripheral Taste System in Inbred Mouse Strains

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    Taster and non-taster mice strains have been used extensively in animal taste research. Inbred mouse strains C57 and FVB have been proposed to be tasters, where as strains 129 and Balb/C are classified as non-tasters. Therefore, evaluating the peripheral taste system in these mice is of great importance to determine if there are morphological differences that might explain the physiological classification. The purpose of the present study was to determine if inbred mice that have been shown to be tasters have a larger number of fungiform papillae, have larger fungiform papillae and have larger taste buds. My work in this study involved counting the number of fungiform papillae from male and female of each strain, utilizing green food dye under light microscopy. I also utilized a scanning electron microscope after tongues were dehydrated in alcohol and Hexamethyldisilazane (HMDS) and sputter coated with gold to evaluate size and shape of fungiform papillae. I used antibodies to troma-1, utilizing indirect immunohistochemistry on tissue sections to evaluate size and shape of taste buds within each strain. Unpaired t-test was used to analyze the results. There was a significant difference in the number of fungiform papillae as seen under light microscopy in the non-taster 129 strain compared to the other strains. Data generated by scanning electron microscope also suggest that the size of the fungiform papillae is significantly smaller in the non-taster Balb/C and 129 strains. Moreover, the 129 strain had the lowest number of fungiform papillae whereas Balb/C mice had the smallest fungiform surface area among the strains studied. We also evaluated whether multiplying fungiform papillae number by the papillary surface area might also be used as an indicator for the size of the receptor field in different mouse strains. Using this method, we showed that non-taster strains had a smaller receptor field area than taster strains. In summary, our study shows that the taster/non-taster phenotype is reflected in the tongue surface morphology among the strains studied

    Uncovering Intratumoral And Intertumoral Heterogeneity Among Single-Cell Cancer Specimens

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    While several tools have been developed to map axes of variation among individual cells, no analogous approaches exist for identifying axes of variation among multicellular biospecimens profiled at single-cell resolution. Developing such an approach is of great translational relevance and interest, as single-cell expression data are now often collected across numerous experimental conditions (e.g., representing different drug perturbation conditions, CRISPR knockdowns, or patients undergoing clinical trials) that need to be compared. In this work, “Phenotypic Earth Mover\u27s Distance” (PhEMD) is presented as a solution to this problem. PhEMD is a general method for embedding a “manifold of manifolds,” in which each datapoint in the higher-level manifold (of biospecimens) represents a collection of points that span a lower-level manifold (of cells). PhEMD is applied to a newly-generated, 300-biospecimen mass cytometry drug screen experiment to map small-molecule inhibitors based on their differing effects on breast cancer cells undergoing epithelial–mesenchymal transition (EMT). These experiments highlight EGFR and MEK1/2 inhibitors as strongly halting EMT at an early stage and PI3K/mTOR/Akt inhibitors as enriching for a drug-resistant mesenchymal cell subtype characterized by high expression of phospho-S6. More generally, these experiments reveal that the final mapping of perturbation conditions has low intrinsic dimension and that the network of drugs demonstrates manifold structure, providing insight into how these single-cell experiments should be computational modeled and visualized. In the presented drug-screen experiment, the full spectrum of perturbation effects could be learned by profiling just a small fraction (11%) of drugs. Moreover, PhEMD could be integrated with complementary datasets to infer the phenotypes of biospecimens not directly profiled with single-cell profiling. Together, these findings have major implications for conducting future drug-screen experiments, as they suggest that large-scale drug screens can be conducted by measuring only a small fraction of the drugs using the most expensive high-throughput single-cell technologies—the effects of other drugs may be inferred by mapping and extending the perturbation space. PhEMD is also applied to patient tumor biopsies to assess intertumoral heterogeneity. Applied to a melanoma dataset and a clear-cell renal cell carcinoma dataset (ccRCC), PhEMD maps tumors similarly to how it maps perturbation conditions as above in order to learn key axes along which tumors vary with respect to their tumor-infiltrating immune cells. In both of these datasets, PhEMD highlights a subset of tumors demonstrating a marked enrichment of exhausted CD8+ T-cells. The wide variability in tumor-infiltrating immune cell abundance and particularly prominent exhausted CD8+ T-cell subpopulation highlights the importance of careful patient stratification when assessing clinical response to T cell-directed immunotherapies. Altogether, this work highlights PhEMD’s potential to facilitate drug discovery and patient stratification efforts by uncovering the network geometry of a large collection of single-cell biospecimens. Our varied experiments demonstrate that PhEMD is highly scalable, compatible with leading batch effect correction techniques, and generalizable to multiple experimental designs, with clear applicability to modern precision oncology efforts
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