1,654 research outputs found

    Investigating the sustainability of careers in academic primary care: a UK survey.

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    This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.The UK National Health Service (NHS) is undergoing institutional reorganisation due to the Health and Social Care Act-2012 with a continued restriction on funding within the NHS and clinically focused academic institutions. The UK Society for Academic Primary Care (SAPC) is examining the sustainability of academic primary care careers within this climate and preliminary qualitative work has highlighted individual and organisational barriers. This study seeks to quantify the current situation for academics within primary care.UK Society for Academic Primary CareNIHR SPCR Fellowshi

    Intersecting Flavor Branes

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    We consider an instance of the AdS/CFT duality where the bulk theory contains an open string tachyon, and study the instability from the viewpoint of the boundary field theory. We focus on the specific example of the AdS_5 X S^5 background with two probe D7 branes intersecting at general angles. For generic angles supersymmetry is completely broken and there is an open string tachyon between the branes. The field theory action for this system is obtained by coupling to N =4 super Yang-Mills two N =2 hyper multiplets in the fundamental representation of the SU(N) gauge group, but with different choices of embedding of the two N=2 subalgebras into N=4. On the field theory side we find a one-loop Coleman-Weinberg instability in the effective potential for the fundamental scalars. We identify a mesonic operator as the dual of the open string tachyon. By AdS/CFT, we predict the tachyon mass for small 't Hooft coupling (large bulk curvature) and confirm that it violates the AdS stability bound.Comment: 36 page

    Metabolomics demonstrates divergent responses of two Eucalyptus species to water stress

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    Past studies of water stress in Eucalyptus spp. generally highlighted the role of fewer than five “important” metabolites, whereas recent metabolomic studies on other genera have shown tens of compounds are affected. There are currently no metabolite profiling data for responses of stress-tolerant species to water stress. We used GC–MS metabolite profiling to examine the response of leaf metabolites to a long (2 month) and severe (Ψpredawn < −2 MPa) water stress in two species of the perennial tree genus Eucalyptus (the mesic Eucalyptus pauciflora and the semi-arid Eucalyptus dumosa). Polar metabolites in leaves were analysed by GC–MS and inorganic ions by capillary electrophoresis. Pressure–volume curves and metabolite measurements showed that water stress led to more negative osmotic potential and increased total osmotically active solutes in leaves of both species. Water stress affected around 30–40% of measured metabolites in E. dumosa and 10–15% in E. pauciflora. There were many metabolites that were affected in E. dumosa but not E. pauciflora, and some that had opposite responses in the two species. For example, in E. dumosa there were increases in five acyclic sugar alcohols and four low-abundance carbohydrates that were unaffected by water stress in E. pauciflora. Re-watering increased osmotic potential and decreased total osmotically active solutes in E. pauciflora, whereas in E. dumosa re-watering led to further decreases in osmotic potential and increases in total osmotically active solutes. This experiment has added several extra dimensions to previous targeted analyses of water stress responses in Eucalyptus, and highlights that even species that are closely related (e.g. congeners) may respond differently to water stress and re-waterin

    Characterization of four subtypes in morphologically normal tissue excised proximal and distal to breast cancer

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    Widespread mammographic screening programs and improved self-monitoring allow for breast cancer to be detected earlier than ever before. Breast-conserving surgery is a successful treatment for select women. However, up to 40% of women develop local recurrence after surgery despite apparently tumor-free margins. This suggests that morphologically normal breast may harbor early alterations that contribute to increased risk of cancer recurrence. We conducted a comprehensive transcriptomic and proteomic analysis to characterize 57 fresh-frozen tissues from breast cancers and matched histologically normal tissues resected proximal to (<2 cm) and distant from (5–10 cm) the primary tumor, using tissues from cosmetic reduction mammoplasties as baseline. Four distinct transcriptomic subtypes are identified within matched normal tissues: metabolic; immune; matrisome/epithelial–mesenchymal transition, and non-coding enriched. Key components of the subtypes are supported by proteomic and tissue composition analyses. We find that the metabolic subtype is associated with poor prognosis (p < 0.001, HR6.1). Examination of genes representing the metabolic signature identifies several genes able to prognosticate outcome from histologically normal tissues. A subset of these have been reported for their predictive ability in cancer but, to the best of our knowledge, these have not been reported altered in matched normal tissues. This study takes an important first step toward characterizing matched normal tissues resected at pre-defined margins from the primary tumor. Unlocking the predictive potential of unexcised tissue could prove key to driving the realization of personalized medicine for breast cancer patients, allowing for more biologically-driven analyses of tissue margins than morphology alone

    Thermodynamics of Holographic Defects

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    Using the AdS/CFT correspondence, we study the thermodynamic properties and the phase diagram of matter fields on (2+1)-dimensional defects coupled to a (3+1)-dimensional N=4 SYM "heat bath". Considering a background magnetic field, (net) quark density, defect "magnitude" δNc\delta N_c and the mass of the matter, we study the defect contribution to the thermodynamic potentials and their first and second derivatives to map the phases and study their physical properties. We find some features that are qualitatively similar to other systems e.g. in (3+1) dimensions and a number of features that are particular to the defect nature, such as its magnetic properties, unexpected properties at T->0 and finite density; and the finite δNc\delta N_c effects, e.g. a diverging susceptibility and vanishing density of states at small temperatures, a physically consistent negative heat capacity and new types of consistent phases.Comment: 33 pages, 16 figures (jpg and pdf), typos fixed and references added, final version published in JHE

    Escherichia coli induces apoptosis and proliferation of mammary cells

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    Mammary cell apoptosis and proliferation were assessed after injection of Escherichia coli into the left mammary quarters of six cows. Bacteriological analysis of foremilk samples revealed coliform infection in the injected quarters of four cows. Milk somatic cell counts increased in these quarters and peaked at 24 h after bacterial injection. Body temperature also increased, peaking at 12 h postinjection, The number of apoptotic cells was significantly higher in the mastitic tissue than in the uninfected control. Expression of Bax and interleukin-1 beta converting enzyme increased in the mastitic tissue at 24 h and 72 h postinfection, whereas Bcl-2 expression decreased at 24 h but did not differ significantly from the control at 72 h postinfection, Induction of matrix metalloproteinase-g, stromelysin-1 and urokinase-type plasminogen activator was also observed in the mastitic tissue. Moreover, cell proliferation increased in the infected tissue, These results demonstrate that Escherichia coli-induced mastitis promotes apoptosis and cell proliferation

    A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

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    Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

    Lectin-like bacteriocins from pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor

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    Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide that is predominantly a homopolymer of d-rhamnose. Structural and biophysical analyses show that recognition of CPA occurs through the C-terminal carbohydrate-binding domain of pyocin L1 and that this interaction is a prerequisite for bactericidal activity. Further to this, we show that the previously described lectin-like bacteriocin putidacin L1 shows a similar carbohydrate-binding specificity, indicating that oligosaccharides containing d-rhamnose and not d-mannose, as was previously thought, are the physiologically relevant ligands for this group of bacteriocins. The widespread inclusion of d-rhamnose in the lipopolysaccharide of members of the genus Pseudomonas explains the unusual genus-specific activity of the lectin-like bacteriocins
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