8,498 research outputs found

    HLA-B*57:01 Allele Prevalence in HIV-infected North American Subjects and the Impact of Allele Testing on the Incidence of Abacavir-associated Hypersensitivity Reaction in HLA-B*57:01-negative Subjects

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    BACKGROUND: The presence of the HLA-B*57:01 allele in HIV-infected subjects is associated with a higher risk of abacavir-associated hypersensitivity reaction (ABC HSR). HLA-B*57:01 allele prevalence varies in different populations, but HLA-B*57:01 testing with immunological confirmation has had a negative predictive value for ABC HSR between 97 and 100%. METHODS: In the ASSURE study (EPZ113734), the HLA-B*57:01 prevalence in virologically suppressed, antiretroviral treatment-experienced, HIV-infected subjects from the United States, including Puerto Rico, was assessed. RESULTS: Three hundred eighty-five subjects were screened; 13 were HLA-B*57:01 positive and 372 were negative. Only HLA-B*57:01-negative, abacavir-naive subjects were eligible to enroll into the ASSURE trial. Eleven of the 13 subjects who possessed the HLA-B*57:01 allele were white, the other 2 were African-American. There was no geographic clustering of HLA-B*57:01-positive subjects, and the incidence correlated roughly with those states with the greatest numbers of subjects screened. Similarly, there was no statistically significant correlation between subjects who possessed or lacked the allele and age, gender, ethnicity or CD4+ T-cell numbers. The incidence of ABC HSR following abacavir initiation was also evaluated. Only 1 of 199 HLA-B*57:01-negative subjects (an African-American male) randomized to receive abacavir-containing treatment developed symptoms consistent with suspected ABC HSR; ABC HSR was not immunologically confirmed. CONCLUSIONS: These findings confirm the utility of HLA-B*57:01 allele testing to reduce the frequency of ABC HSR. The prevalence of HLA-B*57:01 positivity was higher in white than in African-American subjects. In HLA-B*57:01-negative subjects, suspected ABC HSR is very rare, but should lead to discontinuation of abacavir when ABC HSR cannot be definitively excluded from the differential diagnosis. TRIAL REGISTRATION: The ASSURE (EPZ113734) study was registered on ClinicalTrials.gov registration on April 8th 2010 and the registration number is NCT01102972

    Time transfer between the Goddard Optical Research Facility and the U.S. Naval Observatory using 100 picosecond laser pulses

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    A horizontal two-way time comparison link in air between the University of Maryland laser ranging and time transfer equipment at the Goddard Optical Research Facility (GORF) 1.2 m telescope and the Time Services Division of the U.S. Naval Observatory (USNO) was established. Flat mirrors of 25 cm and 30 cm diameter respectively were placed on top of the Washington Cathedral and on a water tower at the Beltsville Agricultural Research Center. Two optical corner reflectors at the USNO reflect the laser pulses back to the GORF. Light pulses of 100 ps duration and an energy of several hundred microjoules are sent at the rate of 10 pulses per second. The detection at the USNO is by means of an RCA C30902E avalanche photodiode and the timing is accomplished by an HP 5370A computing counter and an HP 1000 computer with respect to a 10 pps pulse train from the Master Clock

    Embryonic Pattern Scaling Achieved by Oppositely Directed Morphogen Gradients

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    Morphogens are proteins, often produced in a localised region, whose concentrations spatially demarcate regions of differing gene expression in developing embryos. The boundaries of expression must be set accurately and in proportion to the size of the one-dimensional developing field; this cannot be accomplished by a single gradient. Here, we show how a pair of morphogens produced at opposite ends of a developing field can solve the pattern-scaling problem. In the most promising scenario, the morphogens effectively interact according to the annihilation reaction A+Bβ†’βˆ…A+B\to\emptyset and the switch occurs according to the absolute concentration of AA or BB. In this case embryonic markers across the entire developing field scale approximately with system size; this cannot be achieved with a pair of non-interacting gradients that combinatorially regulate downstream genes. This scaling occurs in a window of developing-field sizes centred at a few times the morphogen decay length.Comment: 24 pages; 11 figures; uses iopar

    Elastic energy of polyhedral bilayer vesicles

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    In recent experiments [M. Dubois, B. Dem\'e, T. Gulik-Krzywicki, J.-C. Dedieu, C. Vautrin, S. D\'esert, E. Perez, and T. Zemb, Nature (London) Vol. 411, 672 (2001)] the spontaneous formation of hollow bilayer vesicles with polyhedral symmetry has been observed. On the basis of the experimental phenomenology it was suggested [M. Dubois, V. Lizunov, A. Meister, T. Gulik-Krzywicki, J. M. Verbavatz, E. Perez, J. Zimmerberg, and T. Zemb, Proc. Natl. Acad. Sci. U.S.A. Vol. 101, 15082 (2004)] that the mechanism for the formation of bilayer polyhedra is minimization of elastic bending energy. Motivated by these experiments, we study the elastic bending energy of polyhedral bilayer vesicles. In agreement with experiments, and provided that excess amphiphiles exhibiting spontaneous curvature are present in sufficient quantity, we find that polyhedral bilayer vesicles can indeed be energetically favorable compared to spherical bilayer vesicles. Consistent with experimental observations we also find that the bending energy associated with the vertices of bilayer polyhedra can be locally reduced through the formation of pores. However, the stabilization of polyhedral bilayer vesicles over spherical bilayer vesicles relies crucially on molecular segregation of excess amphiphiles along the ridges rather than the vertices of bilayer polyhedra. Furthermore, our analysis implies that, contrary to what has been suggested on the basis of experiments, the icosahedron does not minimize elastic bending energy among arbitrary polyhedral shapes and sizes. Instead, we find that, for large polyhedron sizes, the snub dodecahedron and the snub cube both have lower total bending energies than the icosahedron

    Heat to Electricity Conversion by a Graphene Stripe with Heavy Chiral Fermions

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    A conversion of thermal energy into electricity is considered in the electrically polarized graphene stripes with zigzag edges where the heavy chiral fermion (HCF) states are formed. The stripes are characterized by a high electric conductance Ge and by a significant Seebeck coefficient S. The electric current in the stripes is induced due to a non-equilibrium thermal injection of "hot" electrons. This thermoelectric generation process might be utilized for building of thermoelectric generators with an exceptionally high figure of merit Z{\delta}T \simeq 100 >> 1 and with an appreciable electric power densities \sim 1 MW/cm2.Comment: 8 pages, 3 figure

    Penaeid Shrimp in Chesapeake Bay: Population Growth and Black Gill Disease Syndrome

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    Since 1991, the number of penaeid shrimp occurring in Virginia waters of Chesapeake Bay has steadily increased, prompting an interest in developing a fishery. Although development of a shrimp fishery in the Chesapeake Bay region could bring economic benefits, the fishery may be hampered by the presence of a disease syndrome known as shrimp black gill (sBG). The objectives of our study were to (1) describe the spatial distribution and abundance patterns of shrimp in Chesapeake Bay, (2) relate relative abundance of shrimp to habitat characteristics, and (3) determine the presence and seasonality of sBG to better understand disease dynamics in the region. Subadult penaeid shrimp were collected monthly from Virginia waters by trawl from 1991 to 2017, and individuals were identified to species and counted. White shrimp Litopenaeus setiferus were the most numerous species captured, followed by brown shrimp Farfantepenaeus aztecus and pink shrimp F. duorarum. Shrimp were captured primarily from July to December. White shrimp were the only species that exhibited visible signs of sBG, which was first observed in October 2016 (13.4% prevalence); the condition continued into November and recurred the following year. Shrimp with visible signs of gill disease were examined by microscopy, histology, and PCR assay and were diagnosed with infections of a histophagous apostome ciliate, presumably Hyalophysa lynni. Any impacts of sBG on shrimp survival or marketability should be considered in fishery management plans to ensure sustainability of the resource

    The S. pombe translation initiation factor eIF4G is sumoylated and associates with the SUMO protease Ulp2

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    SUMO is a small post-translational modifier, that is attached to lysine residues in target proteins. It acts by altering proteinprotein interactions, protein localisation and protein activity. SUMO chains can also act as substrates for ubiquitination, resulting in proteasome-mediated degradation of the target protein. SUMO is removed from target proteins by one of a number of specific proteases. The processes of sumoylation and desumoylation have well documented roles in DNA metabolism and in the maintenance of chromatin structure. To further analyse the role of this modification, we have purified protein complexes containing the S. pombe SUMO protease, Ulp2. These complexes contain proteins required for ribosome biogenesis, RNA stability and protein synthesis. Here we have focussed on two translation initiation factors that we identified as co-purifying with Ulp2, eIF4G and eIF3h. We demonstrate that eIF4G, but not eIF3h, is sumoylated. This modification is increased under conditions that produce cytoplasmic stress granules. Consistent with this we observe partial co-localisation of eIF4G and SUMO in stressed cells. Using HeLa cells, we demonstrate that human eIF4GI is also sumoylated; in vitro studies indicate that human eIF4GI is modified on K1368 and K1588, that are located in the C-terminal eIF4A- and Mnk-binding sites respectively
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