1,762 research outputs found

    Activity-Dependent β-Adrenergic Modulation of Low Frequency Stimulation Induced LTP in the Hippocampal CA1 Region

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    Abstractβ-Adrenergic receptor activation has a central role in the enhancement of memory formation that occurs during heightened states of emotional arousal. Although β-adrenergic receptor activation may enhance memory formation by modulating long-term potentiation (LTP), a candidate synaptic mechanism involved in memory formation, the cellular basis of this modulation is not fully understood. Here, we report that, in the CA1 region of the hippocampus, β-adrenergic receptor activation selectively enables the induction of LTP during long trains of 5 Hz synaptic stimulation. Protein phosphatase inhibitors mimic the effects of β-adrenergic receptor activation on 5 Hz stimulation–induced LTP, suggesting that activation of noradrenergic systems during emotional arousal may enhance memory formation by inhibiting protein phosphatases that normally oppose the induction of LTP

    Framework programmable platform for the advanced software development workstation. Integration mechanism design document

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    The Framework Programmable Software Development Platform (FPP) is a project aimed at combining effective tool and data integration mechanisms with a model of the software development process in an intelligent integrated software development environment. Guided by this model, this system development framework will take advantage of an integrated operating environment to automate effectively the management of the software development process so that costly mistakes during the development phase can be eliminated

    Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

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    Background: There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods: Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with primary isolates of HIV-1. Results: This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody response. However, the antibodies did not neutralise primary isolates of HIV-1 or the V3-sensitive isolate SF162 using the TZM-bl b-galactosidase assay. Conclusions: MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due to their excellent safety profile for use in humans. This study shows this novel prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques

    Forecasting Evaluation of WindSat in the Coastal Environment

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    WindSat has demonstrated that measurements from polarimetric space-based microwave radiometers can be used to retrieve global ocean surface vector winds. Since the date of launch in 2003, substantial incremental improvements have been made to WindSat data processing, calibration, and retrieval algorithms. The retrievals now have higher resolution, improved wind vector ambiguity removal, and enhanced capability to represent high winds. Utilization of WindSat retrievals (wind vectors, total precipitable water, rainrate and sea surface temperature) will be demonstrated in the context of operational weather forecasting applications, especially the monitoring of topographically-forced winds. Examples will be presented from various parts of the world, including inland seas, midlatitude oceans, the tropics, and the United States. We will illustrate retrievals in extreme high- and extreme low-wind regimes, both of which can be problematic. Rain contamination will be addressed. We will include a comparison of WindSat vector maps to corresponding maps from the QuikScat scatterometer. We will discuss how near-realtime data from WindSat is being transitioned to specific offices within the National Weather Service

    Recent trends in UK insects that inhabit early successional stages of ecosystems

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    Improved recording of less popular groups, combined with new statistical approaches that compensate for datasets that were hitherto too patchy for quantitative analysis, now make it possible to compare recent trends in the status of UK invertebrates other than butterflies. Using BRC datasets, we analysed changes in status between 1992 and 2012 for those invertebrates whose young stages exploit early seral stages within woodland, lowland heath and semi-natural grassland ecosystems, a habitat type that had declined during the 3 decades previous to 1990 alongside a disproportionally high number of Red Data Book species that were dependent on it. Two clear patterns emerged from a meta-analysis involving 299 classifiable species belonging to ten invertebrate taxa: (i) during the past 2 decades, most early seral species that are living near their northern climatic limits in the UK have increased relative to the more widespread members of these guilds whose distributions were not governed by a need for a warm micro-climate; and (ii) independent of climatic constraints, species that are restricted to the early stages of woodland regeneration have fared considerably less well than those breeding in the early seral stages of grasslands or, especially, heathland. The first trend is consistent with predicted benefits for northern edge-of-range species as a result of climate warming in recent decades. The second is consistent with our new assessment of the availability of early successional stages in these three ecosystems since c. 1990. Whereas the proportion and continuity of early seral patches has greatly increased within most semi-natural grasslands and lowland heaths, thanks respectively to agri-environmental schemes and conservation management, the representation of fresh clearings has continued to dwindle within UK woodlands, whose floors are increasingly shaded and ill-suited for this important guild of invertebrates
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