374 research outputs found

    Route of entry-dependent blocks to retroviral replication.

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    Restriction factors are endogenous cellular proteins that block retroviral replication at specific points in the life cycle. Those identified so far include Fvl, Trim5a and TrimCyp. Their characterisation has extended knowledge of retroviral and cellular functions, and has added a new branch to innate immunity. Retroviral susceptibility to Fvl and Trim5a is determined by its capsid, and is manifested in a pre- (Trim5a, TrimCyp) or post- (Fvl) reverse transcription block to replication. Other blocks to replication have been postulated. For example, a novel anti-viral factor, Lv2, is thought to block replication of several primary isolates of HIV-2 in some cell lines. Knowledge of the early steps of virus replication, between entry and nuclear import, is critical to understanding restriction. The intention of the studies described in this thesis was to determine whether alternative routes of virus trafficking might affect susceptibility to Fvl and Trim5a, as well as to the putative Lv2. A system of two receptors was used, Tva800 and Tva950 both permit entry via ASLV envelope protein, but take the virus into the cell by two different endocytic mechanisms. The pathways traversed after binding to Tva800 and Tva950 were investigated and shown not to reroute virions around restriction mediated by Fvl and Trim5a. When virus titration curves were analysed, a distinctive pattern emerged suggesting that entry via Tva800, but not Tva950, requires engagement of more than one receptor- envelope pair. The block to replication caused by the putative factor Lv2 was also analysed. It was concluded that a combination of low surface CD4 expression and poor receptor engagement are the cause of low viral titres in some cell lines, rather than a cellular anti-viral factor per se

    What Happens When Insurers Make Insurance Laws? State Legislative Agendas and the Occupational Makeup of Government

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    Do the occupational backgrounds of politicians affect the government’s agenda? Businesses have long thought so. The first occupational data on state legislators were collected by the Insurance Information Institute, an interest group representing major insurance companies. In this paper, we test one potential motive for these kinds of efforts: the idea that the occupational makeup of governments affects the agendas they pursue, an argument that has been largely neglected in research on politicians’ occupational backgrounds. We focus here on the insurance industry. Using original data, we find that state legislatures with more former insurers consider fewer bills regulating insurance (negative agenda control), that former insurers play a disproportionate role in drafting the insurance bills that are introduced (positive agenda control), and that the bills former insurers introduce tend to be more favorable to the industry than those that their colleagues introduce (positive agenda control). The occupational makeup of legislatures may indeed affect their agendas, as industry groups have long suspected

    Stability Walls in Heterotic Theories

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    We study the sub-structure of the heterotic Kahler moduli space due to the presence of non-Abelian internal gauge fields from the perspective of the four-dimensional effective theory. Internal gauge fields can be supersymmetric in some regions of the Kahler moduli space but break supersymmetry in others. In the context of the four-dimensional theory, we investigate what happens when the Kahler moduli are changed from the supersymmetric to the non-supersymmetric region. Our results provide a low-energy description of supersymmetry breaking by internal gauge fields as well as a physical picture for the mathematical notion of bundle stability. Specifically, we find that at the transition between the two regions an additional anomalous U(1) symmetry appears under which some of the states in the low-energy theory acquire charges. We compute the associated D-term contribution to the four-dimensional potential which contains a Kahler-moduli dependent Fayet-Iliopoulos term and contributions from the charged states. We show that this D-term correctly reproduces the expected physics. Several mathematical conclusions concerning vector bundle stability are drawn from our arguments. We also discuss possible physical applications of our results to heterotic model building and moduli stabilization.Comment: 37 pages, 4 figure

    Response of an Excitatory-Inhibitory Neural Network to External Stimulation: An Application to Image Segmentation

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    Neural network models comprising elements which have exclusively excitatory or inhibitory synapses are capable of a wide range of dynamic behavior, including chaos. In this paper, a simple excitatory-inhibitory neural pair, which forms the building block of larger networks, is subjected to external stimulation. The response shows transition between various types of dynamics, depending upon the magnitude of the stimulus. Coupling such pairs over a local neighborhood in a two-dimensional plane, the resultant network can achieve a satisfactory segmentation of an image into ``object'' and ``background''. Results for synthetic and and ``real-life'' images are given.Comment: 8 pages, latex, 5 figure

    Effects of sleep deprivation on neural functioning: an integrative review

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    Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research
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