HLA and HIV Infection Progression: Application of the Minimum Description Length Principle to Statistical Genetics

The minimum description length (MDL) principle states that the best model to account for some data minimizes the sum of the lengths, in bits, of the descriptions of the model and the residual error. The description length is thus a criterion for model selection. Description-length analysis of HLA alleles from the Chicago MACS cohort enables classification of alleles associated with plasma HIV RNA, an indicator of infection progression. Progression variation is most strongly associated with HLA-B. Individuals without B58s supertype alleles average viral RNA levels 3.6-fold greater than individuals with them.Comment: 17 pages, 1 figur

Decaying Dark Matter from Dark Instantons

We construct an explicit, TeV-scale model of decaying dark matter in which the approximate stability of the dark matter candidate is a consequence of a global symmetry that is broken only by instanton-induced operators generated by a non-Abelian dark gauge group. The dominant dark matter decay channels are to standard model leptons. Annihilation of the dark matter to standard model states occurs primarily through the Higgs portal. We show that the mass and lifetime of the dark matter candidate in this model can be chosen to be consistent with the values favored by fits to data from the PAMELA and Fermi LAT experiments.Comment: 19 pages LaTeX, 3 eps figures. v2,v3: references adde

Towards improved management of coastal submersion crises - CRISMA-WAVE solution as an example of CRISMA Framework application

Coping with various types of natural or man-made hazards the FP7 SECURITY CRISMA project (http://www.crisrnaprojecteu) has designed and developed an experimental software framework allowing building crisis management simulation application. One of the five pilot applications of CRISMA dealing with preparedness to the coastal submersions was developed and implemented using return of experience of the reference Xynthia storm surge event in the Charente Maritime County in France. The paper addresses the generic CRISMA Framework applicability to simulate mitigation effects of a coastal submersion through CRISMA-Wave implementation of a full modelling cycle. The CRISMA-Wave paradigm reflects user needs for simulation of "what-if" scenarios for short and long-term actions and the paper describes in particular its different components : *Simulation of submersion effects at a range of temporal and spatial scales, *Preparedness Planning, *Assessment of impacts depending on scenarios based on options for managing the inundation risks, *Cascading effects and *Evaluation of damages with comparison of submersion defence scenarios based on cost-benefit and multi criteria analysis

Tests of Universality of Baryon Form Factors in Holographic QCD

We describe a new exact relation for large $N_c$ QCD for the long-distance behavior of baryon form factors in the chiral limit, satisfied by all 4D semi-classical chiral soliton models. We use this relation to test the consistency of the structure of two different holographic models of baryons.Comment: 4 pages. Talk presented by MN at Light Cone 2009: Relativistic Hadronic and Particle Physics, 8-13 Jul 2009, Sao Jose dos Campos, Brazi

High resolution HLA analysis reveals independent class I haplotypes and amino-acid motifs protective for multiple sclerosis.

We investigated association between HLA class I and class II alleles and haplotypes, and KIR loci and their HLA class I ligands, with multiple sclerosis (MS) in 412 European American MS patients and 419 ethnically matched controls, using next-generation sequencing. The DRB1*15:01~DQB1*06:02 haplotype was highly predisposing (odds ratio (OR) = 3.98; 95% confidence interval (CI) = 3-5.31; p-value (p) = 2.22E-16), as was DRB1*03:01~DQB1*02:01 (OR = 1.63; CI = 1.19-2.24; p = 1.41E-03). Hardy-Weinberg (HW) analysis in MS patients revealed a significant DRB1*03:01~DQB1*02:01 homozyote excess (15 observed; 8.6 expected; p = 0.016). The OR for this genotype (5.27; CI = 1.47-28.52; p = 0.0036) suggests a recessive MS risk model. Controls displayed no HW deviations. The C*03:04~B*40:01 haplotype (OR = 0.27; CI = 0.14-0.51; p = 6.76E-06) was highly protective for MS, especially in haplotypes with A*02:01 (OR = 0.15; CI = 0.04-0.45; p = 6.51E-05). By itself, A*02:01 is moderately protective, (OR = 0.69; CI = 0.54-0.87; p = 1.46E-03), and haplotypes of A*02:01 with the HLA-B Thr80 Bw4 variant (Bw4T) more so (OR = 0.53; CI = 0.35-0.78; p = 7.55E-04). Protective associations with the Bw4 KIR ligand resulted from linkage disequilibrium (LD) with DRB1*15:01, but the Bw4T variant was protective (OR = 0.64; CI = 0.49-0.82; p = 3.37-04) independent of LD with DRB1*15:01. The Bw4I variant was not associated with MS. Overall, we find specific class I HLA polymorphisms to be protective for MS, independent of the strong predisposition conferred by DRB1*15:01

On the Evaluation of Gluon Condensate Effects in the Holographic Approach to QCD

In holographic QCD the effects of gluonic condensate can be encoded in a suitable deformation of the 5D metric. We develop two different methods for the evaluation of first order perturbative corrections to masses and decay constants of vector resonances in 5D Hard-Wall models of QCD due to small deformations of the metric. They are extracted either from a novel compact form for the first order correction to the vector two-point function, or from perturbation theory for vector bound-state eigenfunctions: the equivalence of the two methods is shown. Our procedures are then applied to flat and to AdS 5D Hard-Wall models; we complement results of existing literature evaluating the corrections to vector decay constant and to two-pion-one-vector couplings: this is particularly relevant to satisfy the sum rules. We concentrate our attention on the effects for the Gasser-Leutwyler coefficients; we show that, as in the Chiral Quark model, the addition of the gluonic condensate improves the consistency, the understanding and the agreement with phenomenology of the holographic model.Comment: 23 pages, three figures, sign error in pion wave function fixed, numerical analysis extended, general conclusions unchange

Massive Pions, Anomalies and Baryons in Holographic QCD

We consider a holographic model of QCD, obtained by a very simple modification of the original construction, which describes at the same time the pion mass, the QCD anomalies and the baryons as topological solitons. We study in detail its phenomenological implications in both the mesonic and baryonic sectors and compare with the observations.Comment: 31 pages, 2 figures; v2: Version published in Nucl. Phys.

Black Diamonds at Brane Junctions

We discuss the properties of black holes in brane-world scenarios where our universe is viewed as a four-dimensional sub-manifold of some higher-dimensional spacetime. We consider in detail such a model where four-dimensional spacetime lies at the junction of several domain walls in a higher dimensional anti-de Sitter spacetime. In this model there may be any number p of infinitely large extra dimensions transverse to the brane-world. We present an exact solution describing a black p-brane which will induce on the brane-world the Schwarzschild solution. This exact solution is unstable to the Gregory-Laflamme instability, whereby long-wavelength perturbations cause the extended horizon to fragment. We therefore argue that at late times a non-rotating uncharged black hole in the brane-world is described by a deformed event horizon in p+4 dimensions which will induce, to good approximation, the Schwarzschild solution in the four-dimensional brane world. When p=2, this deformed horizon resembles a black diamond and more generally for p>2, a polyhedron.Comment: 13 pages, 1 figure, latex, JHEP.cl

Clustering and Alignment of Polymorphic Sequences for HLA-DRB1 Genotyping

Located on Chromosome 6p21, classical human leukocyte antigen genes are highly polymorphic. HLA alleles associate with a variety of phenotypes, such as narcolepsy, autoimmunity, as well as immunologic response to infectious disease. Moreover, high resolution genotyping of these loci is critical to achieving long-term survival of allogeneic transplants. Development of methods to obtain high resolution analysis of HLA genotypes will lead to improved understanding of how select alleles contribute to human health and disease risk. Genomic DNAs were obtained from a cohort of n = 383 subjects recruited as part of an Ulcerative Colitis study and analyzed for HLA-DRB1. HLA genotypes were determined using sequence specific oligonucleotide probes and by next-generation sequencing using the Roche/454 GSFLX instrument. The Clustering and Alignment of Polymorphic Sequences (CAPSeq) software application was developed to analyze next-generation sequencing data. The application generates HLA sequence specific 6-digit genotype information from next-generation sequencing data using MUMmer to align sequences and the R package diffusionMap to classify sequences into their respective allelic groups. The incorporation of Bootstrap Aggregating, Bagging to aid in sorting of sequences into allele classes resulted in improved genotyping accuracy. Using Bagging iterations equal to 60, the genotyping results obtained using CAPSeq when compared with sequence specific oligonucleotide probe characterized 4-digit genotypes exhibited high rates of concordance, matching at 759 out of 766 (99.1%) alleles. © 2013 Ringquist et al