229 research outputs found

    Different Modes of Retrovirus Restriction by Human APOBEC3A and APOBEC3G In Vivo

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    The apolipoprotein B editing complex 3 (A3) cytidine deaminases are among the most highly evolutionarily selected retroviral restriction factors, both in terms of gene copy number and sequence diversity. Primate genomes encode seven A3 genes, and while A3F and 3G are widely recognized as important in the restriction of HIV, the role of the other genes, particularly A3A, is not as clear. Indeed, since human cells can express multiple A3 genes, and because of the lack of an experimentally tractable model, it is difficult to dissect the individual contribution of each gene to virus restriction in vivo. To overcome this problem, we generated human A3A and A3G transgenic mice on a mouse A3 knockout background. Using these mice, we demonstrate that both A3A and A3G restrict infection by murine retroviruses but by different mechanisms: A3G was packaged into virions and caused extensive deamination of the retrovirus genomes while A3A was not packaged and instead restricted infection when expressed in target cells. Additionally, we show that a murine leukemia virus engineered to express HIV Vif overcame the A3G-mediated restriction, thereby creating a novel model for studying the interaction between these proteins. We have thus developed an in vivo system for understanding how human A3 proteins use different modes of restriction, as well as a means for testing therapies that disrupt HIV Vif-A3G interactions

    Accessing elite nurses for research: reflections on the theoretical and practical issues of telephone interviewing

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    Elite groups are interesting as they frequently are powerful (in terms of position, knowledge and influence) and enjoy considerable authority. It is important, therefore, to involve them in research concerned with understanding social contexts and processes. This is particularly pertinent in healthcare, where considerable strategic development and change are features of everyday practice that may be guided or perceived as being guided, by elites. This paper evolved from a study investigating the availability and role of nurses whose remit involved leading nursing research and development within acute NHS Trusts in two health regions in Southern England. The study design included telephone interviews with Directors of Nursing Services during which time the researchers engaged in a reflective analysis of their experiences of conducting research with an `elite' group. Important issues identified were the role of gatekeepers, engagement with elites and the use of the telephone interview method in this context. The paper examines these issues and makes a case for involving executive nurses in further research. The paper also offers strategies to help researchers design and implement telephone interview studies successfully to maximise access to the views and experiences of `hard to reach groups', such as elites, while minimising the associated disruption

    Coexistence of 'alpha+ 208Pb' cluster structures and single-particle excitations in 212Po

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    Excited states in 212Po have been populated by alpha transfer using the 208Pb(18O,14C) reaction at 85MeV beam energy and studied with the EUROBALL IV gamma multidetector array. The level scheme has been extended up to ~ 3.2 MeV excitation energy from the triple gamma coincidence data. Spin and parity values of most of the observed states have been assigned from the gamma angular distributions and gamma -gamma angular correlations. Several gamma lines with E(gamma) < 1 MeV have been found to be shifted by the Doppler effect, allowing for the measurements of the associated lifetimes by the DSAM method. The values, found in the range [0.1-0.6] ps, lead to very enhanced E1 transitions. All the emitting states, which have non-natural parity values, are discussed in terms of alpha-208Pb structure. They are in the same excitation-energy range as the states issued from shell-model configurations.Comment: 21 pages, 19 figures, corrected typos, revised arguments in Sect. III

    Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

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    We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

    Dynamic analysis of repetitive decision-free discreteevent processes: The algebra of timed marked graphs and algorithmic issues

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    A model to analyze certain classes of discrete event dynamic systems is presented. Previous research on timed marked graphs is reviewed and extended. This model is useful to analyze asynchronous and repetitive production processes. In particular, applications to certain classes of flexible manufacturing systems are provided in a companion paper. Here, an algebraic representation of timed marked graphs in terms of reccurrence equations is provided. These equations are linear in a nonconventional algebra, that is described. Also, an algorithm to properly characterize the periodic behavior of repetitive production processes is descrbed. This model extends the concepts from PERT/CPM analysis to repetitive production processes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44155/1/10479_2005_Article_BF02248590.pd
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