844 research outputs found
BPS black holes, the Hesse potential, and the topological string
The Hesse potential is constructed for a class of four-dimensional N=2
supersymmetric effective actions with S- and T-duality by performing the
relevant Legendre transform by iteration. It is a function of fields that
transform under duality according to an arithmetic subgroup of the classical
dualities reflecting the monodromies of the underlying string compactification.
These transformations are not subject to corrections, unlike the
transformations of the fields that appear in the effective action which are
affected by the presence of higher-derivative couplings. The class of actions
that are considered includes those of the FHSV and the STU model. We also
consider heterotic N=4 supersymmetric compactifications. The Hesse potential,
which is equal to the free energy function for BPS black holes, is manifestly
duality invariant. Generically it can be expanded in terms of powers of the
modulus that represents the inverse topological string coupling constant,
, and its complex conjugate. The terms depending holomorphically on
are expected to correspond to the topological string partition function and
this expectation is explicitly verified in two cases. Terms proportional to
mixed powers of and are in principle present.Comment: 28 pages, LaTeX, added comment
A critical role for ATF2 transcription factor in the regulation of E-selectin expression in response to non-endotoxin components of Neisseria meningitidis
Vascular injury is a serious complication of sepsis due to the gram-negative bacterium Neisseria meningitidis. One of the critical early steps in initiating this injury is via the interaction of leucocytes, particularly neutrophils, with adhesion molecules expressed on inflamed endothelium. We have previously demonstrated that both lipopolysaccharide (LPS) and non-LPS components of meningococci can induce very high levels of expression of the vascular endothelial cell adhesion molecule E-selectin, which is critical for early tethering and capture of neutrophils onto endothelium under flow. Using an LPS-deficient strain of meningococcus, we showed that very high levels of expression can be induced in primary endothelial cells, even in the context of weak activation of the major host signal transduction factor [nuclear factor-κB (NF-κB)]. In this study, we show that the particular propensity for N. meningitidis to induce high levels of expression is regulated at a transcriptional level, and demonstrate a significant role for phosphorylation of the ATF2 transcription factor, likely via mitogen-activated protein (MAP) kinases, on the activity of the E-selectin promoter. Furthermore, inhibition of E-selectin expression in response to the lpxA- strain by a p38 inhibitor indicates a significant role of a p38-dependent MAPK signalling pathway in ATF2 activation. Collectively, these data highlight the role that LPS and other bacterial components have in modulating endothelial function and their involvement in the pathogenesis of meningococcal sepsis. Better understanding of these multiple mechanisms induced by complex stimuli such as bacteria, and the specific inflammatory pathways they activate, may lead to improved, focused interventions in both meningococcal and potentially bacterial sepsis more generally
Understanding elite rugby league players' experience of collision, effective contact coaching techniques, and player contact psychology: A focus group study
The current study performed a series of online focus groups to understand elite rugby league players’ experiences of collision. Eighteen rugby league players comprising different playing positions from four teams were recruited to participate in a series of online focus groups, via the Microsoft Team’s platform, facilitated by a moderator. Players were competing in Europe’s elite rugby league competition, the European Super League (ESL), during the 2021 season. All focus group data were transcribed, coded and analysed using reflexive thematic analysis guide to ensure robust exploring, interpreting and reporting through pattern-based analysis. The findings are split into five key themes: 1) the three-man tackle – the perceived optimal defensive strategy with simultaneous contact, 2) not all collisions are the same; matchplay events change the collision intensity, 3) bracing and blindsiding – two factors that influence experiences of collision and concussion, 4) coaching philosophies and orientations, 5) psychological readiness for collision. Collision sports have an inherent risk of injury; however, in some players’ subjective experiences, there are collision types that have a greater association with risk or intensity (blind-sided collisions or long closing distances). It is essential that future research comprehends the effects of these collision types and the further themes
Patterns of primary care and mortality among patients with schizophrenia or diabetes: a cluster analysis approach to the retrospective study of healthcare utilization
Abstract Background Patients with schizophrenia have difficulty managing their medical healthcare needs, possibly resulting in delayed treatment and poor outcomes. We analyzed whether patients reduced primary care use over time, differentially by diagnosis with schizophrenia, diabetes, or both schizophrenia and diabetes. We also assessed whether such patterns of primary care use were a significant predictor of mortality over a 4-year period. Methods The Veterans Healthcare Administration (VA) is the largest integrated healthcare system in the United States. Administrative extracts of the VA's all-electronic medical records were studied. Patients over age 50 and diagnosed with schizophrenia in 2002 were age-matched 1:4 to diabetes patients. All patients were followed through 2005. Cluster analysis explored trajectories of primary care use. Proportional hazards regression modelled the impact of these primary care utilization trajectories on survival, controlling for demographic and clinical covariates. Results Patients comprised three diagnostic groups: diabetes only (n = 188,332), schizophrenia only (n = 40,109), and schizophrenia with diabetes (Scz-DM, n = 13,025). Cluster analysis revealed four distinct trajectories of primary care use: consistent over time, increasing over time, high and decreasing, low and decreasing. Patients with schizophrenia only were likely to have low-decreasing use (73% schizophrenia-only vs 54% Scz-DM vs 52% diabetes). Increasing use was least common among schizophrenia patients (4% vs 8% Scz-DM vs 7% diabetes) and was associated with improved survival. Low-decreasing primary care, compared to consistent use, was associated with shorter survival controlling for demographics and case-mix. The observational study was limited by reliance on administrative data. Conclusion Regular primary care and high levels of primary care were associated with better survival for patients with chronic illness, whether psychiatric or medical. For schizophrenia patients, with or without comorbid diabetes, primary care offers a survival benefit, suggesting that innovations in treatment retention targeting at-risk groups can offer significant promise of improving outcomes.http://deepblue.lib.umich.edu/bitstream/2027.42/78274/1/1472-6963-9-127.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78274/2/1472-6963-9-127.pdfPeer Reviewe
The effect of systematic pediatric care on neonatal mortality and hospitalizations of infants born with oral clefts
<p>Abstract</p> <p>Background</p> <p>Cleft lip and/or palate (CL/P) increase mortality and morbidity risks for affected infants especially in less developed countries. This study aimed at assessing the effects of systematic pediatric care on neonatal mortality and hospitalizations of infants with cleft lip and/or palate (CL/P) in South America.</p> <p>Methods</p> <p>The intervention group included live-born infants with isolated or associated CL/P in 47 hospitals between 2003 and 2005. The control group included live-born infants with CL/P between 2001 and 2002 in the same hospitals. The intervention group received systematic pediatric care between the 7<sup>th </sup>and 28<sup>th </sup>day of life. The primary outcomes were mortality between the 7<sup>th </sup>and 28<sup>th </sup>day of life and hospitalization days in this period among survivors adjusted for relevant baseline covariates.</p> <p>Results</p> <p>There were no significant mortality differences between the intervention and control groups. However, surviving infants with associated CL/P in the intervention group had fewer hospitalization days by about six days compared to the associated control group.</p> <p>Conclusions</p> <p>Early systematic pediatric care may significantly reduce neonatal hospitalizations of infants with CL/P and additional birth defects in South America. Given the large healthcare and financial burden of CL/P on affected families and the relatively low cost of systematic pediatric care, improving access to such care may be a cost-effective public policy intervention.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00097149">NCT00097149</a></p
Vector boson pair production at the LHC
We present phenomenological results for vector boson pair production at the
LHC, obtained using the parton-level next-to-leading order program MCFM. We
include the implementation of a new process in the code, pp -> \gamma\gamma,
and important updates to existing processes. We incorporate fragmentation
contributions in order to allow for the experimental isolation of photons in
\gamma\gamma, W\gamma, and Z\gamma production and also account for gluon-gluon
initial state contributions for all relevant processes. We present results for
a variety of phenomenological scenarios, at the current operating energy of
\sqrt{s} = 7 TeV and for the ultimate machine goal, \sqrt{s} = 14 TeV. We
investigate the impact of our predictions on several important distributions
that enter into searches for new physics at the LHC.Comment: 35 pages, 14 figure
The transcriptional repressor protein NsrR senses nitric oxide directly via a [2Fe-2S] cluster
The regulatory protein NsrR, a member of the Rrf2 family of transcription repressors, is specifically dedicated to sensing nitric oxide (NO) in a variety of pathogenic and non-pathogenic bacteria. It has been proposed that NO directly modulates NsrR activity by interacting with a predicted [Fe-S] cluster in the NsrR protein, but no experimental evidence has been published to support this hypothesis. Here we report the purification of NsrR from the obligate aerobe Streptomyces coelicolor. We demonstrate using UV-visible, near UV CD and EPR spectroscopy that the protein contains an NO-sensitive [2Fe-2S] cluster when purified from E. coli. Upon exposure of NsrR to NO, the cluster is nitrosylated, which results in the loss of DNA binding activity as detected by bandshift assays. Removal of the [2Fe-2S] cluster to generate apo-NsrR also resulted in loss of DNA binding activity. This is the first demonstration that NsrR contains an NO-sensitive [2Fe-2S] cluster that is required for DNA binding activity
GLP-1 receptor signalling promotes β-cell glucose metabolism via mTOR-dependent HIF-1α activation
Glucagon-like peptide-1 (GLP-1) promotes insulin secretion from pancreatic ß-cells in a glucose dependent manner. Several pathways mediate this action by rapid, kinase phosphorylation-dependent, but gene expression-independent mechanisms. Since GLP-1-induced insulin secretion requires glucose metabolism, we aimed to address the hypothesis that GLP-1 receptor (GLP-1R) signalling can modulate glucose uptake and utilization in ß-cells. We have assessed various metabolic parameters after short and long exposure of clonal BRIN-BD11 ß-cells and rodent islets to the GLP-1R agonist Exendin-4 (50 nM). Here we report for the first time that prolonged stimulation of the GLP-1R for 18 hours promotes metabolic reprogramming of ß-cells. This is evidenced by up-regulation of glycolytic enzyme expression, increased rates of glucose uptake and consumption, as well as augmented ATP content, insulin secretion and glycolytic flux after removal of Exendin-4. In our model, depletion of Hypoxia-Inducible Factor 1 alpha (HIF-1a) impaired the effects of Exendin-4 on glucose metabolism, while pharmacological inhibition of Phosphoinositide 3-kinase (PI3K) or mTOR completely abolished such effects. Considering the central role of glucose catabolism for stimulus-secretion coupling in ß-cells, our findings suggest that chronic GLP-1 actions on insulin secretion include elevated ß-cell glucose metabolism. Moreover, our data reveal novel aspects of GLP-1 stimulated insulin secretion involving de novo gene expression
Robotic milking technologies and renegotiating situated ethical relationships on UK dairy farms
Robotic or automatic milking systems (AMS) are novel technologies that take over the labor of dairy farming and reduce the need for human-animal interactions. Because robotic milking involves the replacement of 'conventional' twice-a-day milking managed by people with a system that supposedly allows cows the freedom to be milked automatically whenever they choose, some claim robotic milking has health and welfare benefits for cows, increases productivity, and has lifestyle advantages for dairy farmers. This paper examines how established ethical relations on dairy farms are unsettled by the intervention of a radically different technology such as AMS. The renegotiation of ethical relationships is thus an important dimension of how the actors involved are re-assembled around a new technology. The paper draws on in-depth research on UK dairy farms comparing those using conventional milking technologies with those using AMS. We explore the situated ethical relations that are negotiated in practice, focusing on the contingent and complex nature of human-animal-technology interactions. We show that ethical relations are situated and emergent, and that as the identities, roles, and subjectivities of humans and animals are unsettled through the intervention of a new technology, the ethical relations also shift. © 2013 Springer Science+Business Media Dordrecht
A Twist in the Dyon Partition Function
In four dimensional string theories with N=4 and N=8 supersymmetries one can
often define twisted index in a subspace of the moduli space which captures
additional information on the partition function than the ones contained in the
usual helicity trace index. We compute several such indices in type IIB string
theory on K3 x T^2 and T^6, and find that they share many properties with the
usual helicity trace index that captures the spectrum of quarter BPS states in
N=4 supersymmetric string theories. In particular the partition function is a
modular form of a subgroup of Sp(2,Z) and the jumps across the walls of
marginal stability are controlled by the residues at the poles of the partition
function. However for large charges the logarithm of this index grows as 1/n
times the entropy of a black hole carrying the same charges where n is the
order of the symmetry generator that is used to define the twisted index. We
provide a macroscopic explanation of this phenomenon using quantum entropy
function formalism. The leading saddle point corresponding to the attractor
geometry fails to contribute to the twisted index, but a Z_n orbifold of the
attractor geometry produces the desired contribution.Comment: LaTeX file, 35 pages; v2: references adde
- …