179 research outputs found
Holographic Kondo Model in Various Dimensions
We study the addition of localised impurities to U(N) Supersymmetric
Yang-Mills theories in (p+1)-dimensions by using the gauge/gravity
correspondence. From the gravity side, the impurities are introduced by
considering probe D(8-p)-branes extendingalong the time and radial directions
and wrapping an (7-p)-dimensional submanifold of the internal (8-p)-sphere, so
that the degrees of freedom are point-like from the gauge theory perspective.
We analyse both the configuration in which the branes generate straight flux
tubes -corresponding to actual single impurities - and the one in which
connected flux tubes are created- corresponding to dimers. We discuss the
thermodynamics of both the configurations and the related phase transition. In
particular, the specific heat of the straight flux-tube configuration is
negative for p<3, while it is never the case for the connected one. We study
the stability of the system by looking at the impurity fluctuations. Finally,
we characterise the theory by computing one- and two-point correlators of the
gauge theory operators dual to the impurity fluctuations. Because of the
underlying generalised conformal structure, such correlators can be expressed
in terms of an effective coupling constant (which runs because of its
dimensionality) and a generalised conformal dimension.Comment: 56 pages, 3 figures; v2: typos correcte
Holography for Einstein-Maxwell-dilaton theories from generalized dimensional reduction
We show that a class of Einstein-Maxwell-Dilaton (EMD) theories are related
to higher dimensional AdS-Maxwell gravity via a dimensional reduction over
compact Einstein spaces combined with continuation in the dimension of the
compact space to non-integral values (`generalized dimensional reduction').
This relates (fairly complicated) black hole solutions of EMD theories to
simple black hole/brane solutions of AdS-Maxwell gravity and explains their
properties. The generalized dimensional reduction is used to infer the
holographic dictionary and the hydrodynamic behavior for this class of theories
from those of AdS. As a specific example, we analyze the case of a black brane
carrying a wave whose universal sector is described by gravity coupled to a
Maxwell field and two neutral scalars. At thermal equilibrium and finite
chemical potential the two operators dual to the bulk scalar fields acquire
expectation values characterizing the breaking of conformal and generalized
conformal invariance. We compute holographically the first order transport
coefficients (conductivity, shear and bulk viscosity) for this system.Comment: v2, Important additions: (1) discussion of the entropy current, (2)
postulated zeta/eta bound is generically violated. Some comments and
references added, typos corrected. 50 page
Z-extremization and F-theorem in Chern-Simons matter theories
The three dimensional exact R symmetry of N=2 SCFTs extremizes the partition
function localized on a three sphere. Here we verify this statement at weak
coupling. We give a detailed analysis for two classes of models. The first one
is an SU(N)_k gauge theory at large k with both fundamental and adjoint matter
fields, while the second is a flavored version of the ABJ theory, where the CS
levels are large but they do not necessarily sum up to zero. We study in both
cases superpotential deformations and compute the R charges at different fixed
points. When these fixed points are connected by an RG flow we explicitly
verify that the free energy decreases at the endpoints of the flow between the
fixed points, corroborating the conjecture of an F-theorem in three dimensions.Comment: 28 pages, 3 figures, JHEP.cls, minor corrections, references adde
The use of a P. falciparum specific coiled-coil domain to construct a self-assembling protein nanoparticle vaccine to prevent malaria.
The parasitic disease malaria remains a major global public health concern and no truly effective vaccine exists. One approach to the development of a malaria vaccine is to target the asexual blood stage that results in clinical symptoms. Most attempts have failed. New antigens such as P27A and P27 have emerged as potential new vaccine candidates. Multiple studies have demonstrated that antigens are more immunogenic and are better correlated with protection when presented on particulate delivery systems. One such particulate delivery system is the self-assembling protein nanoparticle (SAPN) that relies on coiled-coil domains of proteins to form stable nanoparticles. In the past we have used de novo designed amino acid domains to drive the formation of the coiled-coil scaffolds which present the antigenic epitopes on the particle surface.
Here we use naturally occurring domains found in the tex1 protein to form the coiled-coil scaffolding of the nanoparticle. Thus, by engineering P27A and a new extended form of the coiled-coil domain P27 onto the N and C terminus of the SAPN protein monomer we have developed a particulate delivery system that effectively displays both antigens on a single particle that uses malaria tex1 sequences to form the nanoparticle scaffold. These particles are immunogenic in a murine model and induce immune responses similar to the ones observed in seropositive individuals in malaria endemic regions.
We demonstrate that our P27/P27A-SAPNs induce an immune response akin to the one in seropositive individuals in Burkina Faso. Since P27 is highly conserved among different Plasmodium species, these novel SAPNs may even provide cross-protection between Plasmodium falciparum and Plasmodium vivax the two major human malaria pathogens. As the SAPNs are also easy to manufacture and store they can be delivered to the population in need without complication thus providing a low cost malaria vaccine
The Nuclear Transcription Factor PKNOX2 Is a Candidate Gene for Substance Dependence in European-Origin Women
Substance dependence or addiction is a complex environmental and genetic disorder that results in serious health and socio-economic consequences. Multiple substance dependence categories together, rather than any one individual addiction outcome, may explain the genetic variability of such disorder. In our study, we defined a composite substance dependence phenotype derived from six individual diagnoses: addiction to nicotine, alcohol, marijuana, cocaine, opiates or other drugs as a whole. Using data from several genomewide case-control studies, we identified a strong (Odds ratio = 1.77) and significant (p-value = 7E-8) association signal with a novel gene, PBX/knotted 1 homeobox 2 (PKNOX2), on chromosome 11 with the composite phenotype in European-origin women. The association signal is not as significant when individual outcomes for addiction are considered, or in males or African-origin population. Our findings underscore the importance of considering multiple addiction types and the importance of considering population and gender stratification when analyzing data with heterogeneous population
Discrepant comorbidity between minority and white suicides: a national multiple cause-of-death analysis
Abstract
Background
Clinician training deficits and a low and declining autopsy rate adversely impact the quality of death certificates in the United States. Self-report and records data for the general population indicate that proximate mental and physical health of minority suicides was at least as poor as that of white suicides.
Methods
This cross-sectional mortality study uses data from Multiple Cause-of-Death (MCOD) public use files for 1999–2003 to describe and evaluate comorbidity among black, Hispanic, and white suicides. Unintentional injury decedents are the referent for multivariate analyses.
Results
One or more mentions of comorbid psychopathology are documented on the death certificates of 8% of white male suicides compared to 4% and 3% of black and Hispanic counterparts, respectively. Corresponding female figures are 10%, 8%, and 6%. Racial-ethnic discrepancies in the prevalence of comorbid physical disease are more attenuated. Cross-validation with National Violent Death Reporting System data reveals high relative underenumeration of comorbid depression/mood disorders and high relative overenumeration of schizophrenia on the death certificates of both minorities. In all three racial-ethnic groups, suicide is positively associated with depression/mood disorders [whites: adjusted odds ratio (AOR) = 31.9, 95% CI = 29.80–34.13; blacks: AOR = 60.9, 95% CI = 42.80–86.63; Hispanics: AOR = 34.7, 95% CI = 23.36–51.62] and schizophrenia [whites: AOR = 2.4, 95% CI = 2.07–2.86; blacks: AOR = 4.2, 95% CI = 2.73–6.37; Hispanics: AOR = 4.1, 95% CI = 2.01–8.22]. Suicide is positively associated with cancer in whites [AOR = 1.8, 95% CI = 1.69–1.93] and blacks [AOR = 1.8, 95% CI = 1.36–2.48], but not with HIV or alcohol and other substance use disorders in any group under review.
Conclusion
The multivariate analyses indicate high consistency in predicting suicide-associated comorbidities across racial-ethnic groups using MCOD data. However, low prevalence of documented comorbid psychopathology in suicides, and concomitant racial-ethnic discrepancies underscore the need for training in death certification, and routinization and standardization of timely psychological autopsies in all cases of suicide, suspected suicide, and other traumatic deaths of equivocal cause
The multiplicity of malaria transmission: a review of entomological inoculation rate measurements and methods across sub-Saharan Africa
Plasmodium falciparum malaria is a serious tropical disease that causes more than one million deaths each year, most of them in Africa. It is transmitted by a range of Anopheles mosquitoes and the risk of disease varies greatly across the continent. The "entomological inoculation rate" is the commonly-used measure of the intensity of malaria transmission, yet the methods used are currently not standardized, nor do they take the ecological, demographic, and socioeconomic differences across populations into account. To better understand the multiplicity of malaria transmission, this study examines the distribution of transmission intensity across sub-Saharan Africa, reviews the range of methods used, and explores ecological parameters in selected locations. It builds on an extensive geo-referenced database and uses geographical information systems to highlight transmission patterns, knowledge gaps, trends and changes in methodologies over time, and key differences between land use, population density, climate, and the main mosquito species. The aim is to improve the methods of measuring malaria transmission, to help develop the way forward so that we can better assess the impact of the large-scale intervention programmes, and rapid demographic and environmental change taking place across Africa
Genome sequence analyses of two isolates from the recent Escherichia coli outbreak in Germany reveal the emergence of a new pathotype: Entero-Aggregative-Haemorrhagic Escherichia coli (EAHEC)
The genome sequences of two Escherichia coli O104:H4 strains derived from two different patients of the 2011 German E. coli outbreak were determined. The two analyzed strains were designated E. coli GOS1 and GOS2 (German outbreak strain). Both isolates comprise one chromosome of approximately 5.31 Mbp and two putative plasmids. Comparisons of the 5,217 (GOS1) and 5,224 (GOS2) predicted protein-encoding genes with various E. coli strains, and a multilocus sequence typing analysis revealed that the isolates were most similar to the entero-aggregative E. coli (EAEC) strain 55989. In addition, one of the putative plasmids of the outbreak strain is similar to pAA-type plasmids of EAEC strains, which contain aggregative adhesion fimbrial operons. The second putative plasmid harbors genes for extended-spectrum β-lactamases. This type of plasmid is widely distributed in pathogenic E. coli strains. A significant difference of the E. coli GOS1 and GOS2 genomes to those of EAEC strains is the presence of a prophage encoding the Shiga toxin, which is characteristic for enterohemorrhagic E. coli (EHEC) strains. The unique combination of genomic features of the German outbreak strain, containing characteristics from pathotypes EAEC and EHEC, suggested that it represents a new pathotype Entero-Aggregative-Haemorrhagic Escherichiacoli (EAHEC)
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