168 research outputs found
To what degree have the non-police public services adopted the National Intelligence Model? : what benefits could the National Intelligence Model deliver?
It is claimed that the National Intelligence Model (NIM) consolidated intelligence-led policing principles in investigative practice and decision making in British policing. Subsequently, encouraged by the Home Office, the NIM was adopted by a number of other public services with an investigative capability. However, that transfer took place without a sufficiently rigorous evaluation of the modelâs value to the police service and without any meaningful analysis of its relevance to the investigative functions of other public sector agencies. This research examined the adoption of the NIM by three public sector bodies: The Department for Work and Pensions (DWP), The Identity and Passport Service (IPS) and the Driving Standards Agency (DSA). It drew on archival materials, associated literature and the analysis of semi-structured interviews with the personnel of these and associated agencies. Research respondents also assessed a simplified version of the NIM that was designed to remove many of the original modelâs inconsistencies and ambiguities. The research identified that the reviewed public services are not compliant with the NIM minimum standards and that the model has not delivered any meaningful improvement in the consistency of process, investigative efficiency, improved partnership working, or in fraud reduction in those agencies. The NIM failed because of perceived complexity, the language of the model and supplementary guidance; its exclusive âfitâ with the police; and a suspicion by the agenciesâ personnel that its adoption was intended as a performance management and governance tool. Moreover, the revised version of the NIMâs minimum standards did not improve comprehension or conformity, or resolve the modelâs perceived police bias. It was concluded that the model is not fit for purpose for the agencies studied and that an alternative model that is more finely tuned to the needs of those agencies is required.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Correlation between pathological findings and bacteriological culture on paratuberculous cattle.
ABSTRACT - Paratuberculosis (PTB) is a chronic enteritis determined by Mycobacterium avium subsp. paratuberculosis (Map) that affects ruminants. Three crossbred dairy cattle with clinical PTB were necropsied; tissue samples were collected and processed for histopathology and culture. Intestinal lesions were characterized in three levels of severity (mild, moderate and severe) by gross examination. Gross examination, microscopy and tissue culture were analyzed and compared. Mean tissue culture sensitivity was 66.6%. Map was recovered from 42.8% of intestinal mild lesions, 55.5% of intestinal moderate lesions, and 100% of severe intestine lesions. The results indicate a significant correlation between the level of lesions severity and the isolation of Map
Probing the high-redshift universe with SPICA: Toward the epoch of reionisation and beyond
With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (ÎŒ LIR > 1013 Lâ, where ÎŒ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICAâs far-infrared spectrometer SAFARI, which will probe a spectral range (35â230 ÎŒm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 â 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARIâs ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI
Polarity Changes in the Transmembrane Domain Core of HIV-1 Vpu Inhibits Its Anti-Tetherin Activity
Tetherin (BST-2/CD317) is an interferon-inducible antiviral protein that restricts the release of enveloped viruses from infected cells. The HIV-1 accessory protein Vpu can efficiently antagonize this restriction. In this study, we analyzed mutations of the transmembrane (TM) domain of Vpu, including deletions and substitutions, to delineate amino acids important for HIV-1 viral particle release and in interactions with tetherin. The mutants had similar subcellular localization patterns with that of wild-type Vpu and were functional with respect to CD4 downregulation. We showed that the hydrophobic binding surface for tetherin lies in the core of the Vpu TM domain. Three consecutive hydrophobic isoleucine residues in the middle region of the Vpu TM domain, I15, I16 and I17, were important for stabilizing the tetherin binding interface and determining its sensitivity to tetherin. Changing the polarity of the amino acids at these positions resulted in severe impairment of Vpu-induced tetherin targeting and antagonism. Taken together, these data reveal a model of specific hydrophobic interactions between Vpu and tetherin, which can be potentially targeted in the development of novel anti-HIV-1 drugs
The Structure of the Chemokine Receptor CXCR1 in Phospholipid Bilayers and Interactions with IL-8
CXCR1 is one of two high-affinity receptors for the CXC chemokine interleukin-8 (IL-8), a major mediator of immune and inflammatory responses implicated in many disorders, including tumor growth(1-3). IL-8, released in response to inflammatory stimuli, binds to the extracellular side of CXCR1. The ligand-activated intracellular signaling pathways result in neutrophil migration to the site of inflammation(2). CXCR1 is a class-A, rhodopsin-like G-protein-coupled receptor (GPCR), the largest class of integral membrane proteins responsible for cellular signal transduction and targeted as drug receptors(4-7). Despite its importance, its molecular mechanism is poorly understood due to the limited structural information available. Recently, structure determination of GPCRs has advanced by tailoring the receptors with stabilizing mutations, insertion of the protein T4 lysozyme and truncations of their amino acid sequences(8), as well as addition of stabilizing antibodies and small molecules(9) that facilitate crystallization in cubic phase monoolein mixtures(10). The intracellular loops of GPCRs are critical for G-protein interactions(11) and activation of CXCR1 involves both N-terminal residues and extracellular loops(2,12,13). Our previous NMR studies indicate that IL-8 binding to the N-terminal residues is mediated by the membrane, underscoring the importance of the phospholipid bilayer for physiological activity(14). Here we report the three-dimensional structure of human CXCR1 determined by NMR spectroscopy. The receptor is in liquid crystalline phospholipid bilayers, without modification of its amino acid sequence and under physiological conditions. Features important for intracellular G-protein activation and signal transduction are revealed
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The European Solar Telescope
The European Solar Telescope (EST) is a project aimed at studying the magnetic connectivity of the solar atmosphere, from the deep photosphere to the upper chromosphere. Its design combines the knowledge and expertise gathered by the European solar physics community during the construction and operation of state-of-the-art solar telescopes operating in visible and near-infrared wavelengths: the Swedish 1m Solar Telescope, the German Vacuum Tower Telescope and GREGOR, the French TĂ©lescope HĂ©liographique pour l'Ătude du MagnĂ©tisme et des InstabilitĂ©s Solaires, and the Dutch Open Telescope. With its 4.2 m primary mirror and an open configuration, EST will become the most powerful European ground-based facility to study the Sun in the coming decades in the visible and near-infrared bands. EST uses the most innovative technological advances: the first adaptive secondary mirror ever used in a solar telescope, a complex multi-conjugate adaptive optics with deformable mirrors that form part of the optical design in a natural way, a polarimetrically compensated telescope design that eliminates the complex temporal variation and wavelength dependence of the telescope Mueller matrix, and an instrument suite containing several (etalon-based) tunable imaging spectropolarimeters and several integral field unit spectropolarimeters. This publication summarises some fundamental science questions that can be addressed with the telescope, together with a complete description of its major subsystems
Viruses: incredible nanomachines. New advances with filamentous phages
During recent decades, bacteriophages have been at the cutting edge of new developments in molecular biology, biophysics, and, more recently, bionanotechnology. In particular filamentous viruses, for example bacteriophage M13, have a virion architecture that enables precision building of ordered and defect-free two and three-dimensional structures on a nanometre scale. This could not have been possible without detailed knowledge of coat protein structure and dynamics during the virus reproduction cycle. The results of the spectroscopic studies conducted in our group compellingly demonstrate a critical role of membrane embedment of the protein both during infectious entry of the virus into the host cell and during assembly of the new virion in the host membrane. The protein is effectively embedded in the membrane by a strong C-terminal interfacial anchor, which together with a simple tilt mechanism and a subtle structural adjustment of the extreme end of its N terminus provides favourable thermodynamical association of the protein in the lipid bilayer. This basic physicochemical rule cannot be violated and any new bionanotechnology that will emerge from bacteriophage M13 should take this into account
Orientation and dynamics of transmembrane peptides: the power of simple models
In this review we discuss recent insights obtained from well-characterized model systems into the factors that determine the orientation and tilt angles of transmembrane peptides in lipid bilayers. We will compare tilt angles of synthetic peptides with those of natural peptides and proteins, and we will discuss how tilt can be modulated by hydrophobic mismatch between the thickness of the bilayer and the length of the membrane spanning part of the peptide or protein. In particular, we will focus on results obtained on tryptophan-flanked model peptides (WALP peptides) as a case study to illustrate possible consequences of hydrophobic mismatch in molecular detail and to highlight the importance of peptide dynamics for the experimental determination of tilt angles. We will conclude with discussing some future prospects and challenges concerning the use of simple peptide/lipid model systems as a tool to understand membrane structure and function
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