370 research outputs found

    Doctor of Philosophy

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    dissertationUpon infecting a host, viruses immediately face restriction by the host immune system, including innate and adaptive responses. To mediate efficient replication, viruses have evolved a number of mechanisms to subvert and bypass the host immune responses. Among the earliest immune protections encountered by viruses are a group of cellintrinsic immunity proteins called "restriction factors." Restriction factors have been identified that, if not counteracted, are capable of inhibiting viral replication throughout the viral life cycle. One of the primary mechanisms utilized to counteract these restrictions is the manipulation of the cellular ubiquitin ligase system to induce the directed and specific degradation of these cellular factors. In the case of primate lentiviruses (HIVs and SIVs), four proteins (Vif, Vpu, Vpr, and Vpx) have been shown to alter the specificity of this cellular degradation machinery to target restriction factors. In this study, we explore the molecular interaction between the paralogous proteins Vpr (encoded by all primate lentiviruses) and Vpx (encoded by HIV-2 and some SIVs), the cellular ubiquitin ligase composed of Cul4-Roc1-DDB1- DCAF1 and the restriction factors they target for degradation (Mus81 in the case of Vpr and SAMHD1 in the case of Vpx). Through mutation of DCAF1, the substrate specificity factor for the ubiquitin ligase complex, to which Vpr and Vpx are known to directly interact, we show that although they share a high degree of homology, Vpr and Vpx interact with DCAF1 differently. In addition, through the generation of chimeric Vpriv Vpx proteins, we explore the molecular determinants of Vpr and Vpx substrate specificity. To this end, we demonstrate that manipulation of Cul4-DCAF1 substrate specificity by Vpr and Vpx is mediated by nonlinear determinants within the respective proteins, in contrast to previously proposed models. Finally, we demonstrate that Vpr induces the degradation of Mus81 in a manner independent of the induction of G2 arrest, in contrast to recent reports

    RACE pulls for shared control

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    Maintaining and supporting an aircraft fleet, in a climate of reduced manpower and financial resources, dictates effective utilization of robotics and automation technologies. To help develop a winning robotics and automation program the Air Force Logistics Command created the Robotics and Automation Center of Excellence (RACE). RACE is a command wide focal point. Race is an organic source of expertise to assist the Air Logistic Center (ALC) product directorates in improving process productivity through the judicious insertion of robotics and automation technologies. RACE is a champion for pulling emerging technologies into the aircraft logistic centers. One of those technology pulls is shared control. Small batch sizes, feature uncertainty, and varying work load conspire to make classic industrial robotic solutions impractical. One can view ALC process problems in the context of space robotics without the time delay. The ALC's will benefit greatly from the implementation of a common architecture that supports a range of control actions from fully autonomous to teleoperated. Working with national laboratories and private industry, we hope to transition shared control technology to the depot floor. This paper provides an overview of the RACE internal initiatives and customer support, with particular emphasis on production processes that will benefit from shared control technology

    On Representations of Semigroups Having Hypercube-like Cayley Graphs

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    The $n-dimensional hypercube, or n-cube, is the Cayley graph of the Abelian group Z2n. A number of combinatorially-interesting groups and semigroups arise from modified hypercubes. The inherent combinatorial properties of these groups and semigroups make them useful in a number of contexts, including coding theory, graph theory, stochastic processes, and even quantum mechanics. In this paper, particular groups and semigroups whose Cayley graphs are generalizations of hypercubes are described, and their irreducible representations are characterized. Constructions of faithful representations are also presented for each semigroup. The associated semigroup algebras are realized within the context of Clifford algebras

    Evidence for 10^18-eV neutral particles from the direction of Cygnus X-3

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    Journal ArticleAnalysis of the cumulative Fly's Eye data reveals an excess of air showers from the direction of Cygnus X-3 at energies above 0.5 x 10^18 eV. No point source has previously been identified at such high energies. The probability of this excess arising as a chance clustering of isotropic cosmic rays is 6 . 5 x 10^-4 . The inferred signal flux is (2.0 ± 0.6) x 10&-17 particles/cm2 s. The Cygnus X-3 4.8-h periodicity is weakly present in the data

    Southern Hemisphere Observations of a 101810^{18}eV Cosmic Ray Source Near the Direction of the Galactic Centre

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    We report on an analysis of data from the southern hemisphere SUGAR cosmic ray detector. We confirm the existence of an excess of 101810^{18}eV cosmic rays from a direction close to the Galactic Centre, first reported by the AGASA group. We find that the signal is consistent with that from a point source, and we find no evidence for an excess of cosmic rays coming from the direction of the Galactic Centre itself.Comment: 14 pages including 5 postscript figures, corrected the title (replaced "Cosmic Ray Source" instead of "Cosmic Ray"

    The non-linearity between <ln A> and <Xmax> induced by the acceptance of fluorescence telescopes

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    The measurement of the average depth of the shower maximum is the most commonly used observable for the possible inference of the primary cosmic-ray mass composition. Currently, different experimental Collaborations process and present their data not in the same way, leading to problems in the comparability and interpretation of the results. Whereas is expected to be proportional to in ideal conditions, we demonstrate that the finite field-of-view of fluorescence telescopes plus the attenuation in the atmosphere can introduce a non-linearity into this relation, which is specific for each particular detector setup

    Methods of Sewage Disposal for Country Homes.

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    Particle astrophysics

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    The following scientific areas are reviewed: (1) cosmology and particle physics (particle physics and the early universe, dark matter, and other relics); (2) stellar physics and particles (solar neutrinos, supernovae, and unconventional particle physics); (3) high energy gamma ray and neutrino astronomy; (4) cosmic rays (space and ground observations). Highest scientific priorities for the next decade include implementation of the current program, new initiatives, and longer-term programs. Essential technological developments, such as cryogenic detectors of particles, new solar neutrino techniques, and new extensive air shower detectors, are discussed. Also a certain number of institutional issues (the funding of particle astrophysics, recommended funding mechanisms, recommended facilities, international collaborations, and education and technology) which will become critical in the coming decade are presented

    Proton-air inelastic cross section at S(1/2) = 30 TeV

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    The distribution of the maxima of high energy cosmic ray induced extensive air showers in the atmosphere was measured as a function of atmospheric depth. From the exponential tail of this distribution, it was determined that the proton-air inelastic cross section at 30 TeV center-of-mass energy to be 540 + or - 40mb
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