Multiple testing for SNP-SNP interactions

Most genetic diseases are complex, i.e. associated to combinations of SNPs rather than individual SNPs. In the last few years, this topic has often been addressed in terms of SNP-SNP interaction patterns given as expressions linked by logical operators. Methods for multiple testing in high-dimensional settings can be applied when many SNPs are considered simultaneously. However, another less well-known multiple testing problem arises within a fixed subset of SNPs when the logic expression is chosen optimally. In this article, we propose a general asymptotic approach for deriving the distribution of the maximally selected chi-square statistic in various situations. We show how this result can be used for testing logic expressions - in particular SNP-SNP interaction patterns - while controlling for multiple comparisons. Simulations show that our method provides multiple testing adjustment when the logic expression is chosen such as to maximize the statistic. Its benefit is demonstrated through an application to a real dataset from a large population-based study considering allergy and asthma in KORA. An implementation of our method is available from the Comprehensive R Archive Network (CRAN) as R package 'SNPmaxsel'

Nuclear magnetic resonance measurements reveal the origin of the Debye process in monohydroxy alcohols

Monohydroxy alcohols show a structural relaxation and at longer time scales a Debye-type dielectric peak. From spin-lattice relaxation experiments using different nuclear probes an intermediate, slower-than-structural dynamics is identified for n-butanol. Based on these findings and on diffusion measurements, a model of self-restructuring, transient chains is proposed. The model is demonstrated to explain consistently the so far puzzling observations made for this class of hydrogen-bonded glass forming liquids.Comment: 4 pages, 4 figure

Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting diets (FDs) and ketogenic diets (KDs) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KDs and FDs on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate whether a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression. METHODS: This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing-remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions: a KD with a restricted carbohydrate intake of 20-40 g/day; a FD with a 7-day fast every 6 months and 14-h daily intermittent fasting in between; and a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed. DISCUSSION: Preclinical data suggest that a KD and a FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and a FD on disease progression of MS

Classical and Quantum Gravity in 1+1 Dimensions, Part I: A Unifying Approach

We provide a concise approach to generalized dilaton theories with and without torsion and coupling to Yang-Mills fields. Transformations on the space of fields are used to trivialize the field equations locally. In this way their solution becomes accessible within a few lines of calculation only. In this first of a series of papers we set the stage for a thorough global investigation of classical and quantum aspects of more or less all available 2D gravity-Yang-Mills models.Comment: 24 pages, no figures, some sign errors in Eqs. 52--59 have been corrected (according to the Erratum

Two-dimensional interactions between a BF-type theory and a collection of vector fields

Consistent interactions that can be added to a two-dimensional, free abelian gauge theory comprising a special class of BF-type models and a collection of vector fields are constructed from the deformation of the solution to the master equation based on specific cohomological techniques. The deformation procedure modifies the Lagrangian action, the gauge transformations, as well as the accompanying algebra of the interacting model.Comment: LaTeX 2e, 31 page

Subdiffusion and lateral diffusion coefficient of lipid atoms and molecules in phospholipid bilayers

We use a long, all-atom molecular dynamics (MD) simulation combined with theoretical modeling to investigate the dynamics of selected lipid atoms and lipid molecules in a hydrated diyristoyl-phosphatidylcholine (DMPC) lipid bilayer. From the analysis of a 0.1 $\mu$s MD trajectory we find that the time evolution of the mean square displacement, [\delta{r}(t)]^2, of lipid atoms and molecules exhibits three well separated dynamical regions: (i) ballistic, with [\delta{r}(t)]^2 ~ t^2 for t < 10 fs; (ii) subdiffusive, with [\delta{r}(t)]^2 ~ t^{\beta} with \beta<1, for 10 ps < t < 10 ns; and (iii) Fickian diffusion, with [\delta{r}(t)]^2 ~ t for t > 30 ns. We propose a memory function approach for calculating [\delta{r}(t)]^2 over the entire time range extending from the ballistic to the Fickian diffusion regimes. The results are in very good agreement with the ones from the MD simulations. We also examine the implications of the presence of the subdiffusive dynamics of lipids on the self-intermediate scattering function and the incoherent dynamics structure factor measured in neutron scattering experiments.Comment: Submitted to Phys. Rev.

On the Canonical Reduction of Spherically Symmetric Gravity

In a thorough paper Kuchar has examined the canonical reduction of the most general action functional describing the geometrodynamics of the maximally extended Schwarzschild geometry. This reduction yields the true degrees of freedom for (vacuum) spherically symmetric general relativity. The essential technical ingredient in Kuchar's analysis is a canonical transformation to a certain chart on the gravitational phase space which features the Schwarzschild mass parameter $M_{S}$, expressed in terms of what are essentially Arnowitt-Deser-Misner variables, as a canonical coordinate. In this paper we discuss the geometric interpretation of Kuchar's canonical transformation in terms of the theory of quasilocal energy-momentum in general relativity given by Brown and York. We find Kuchar's transformation to be a ``sphere-dependent boost to the rest frame," where the ``rest frame'' is defined by vanishing quasilocal momentum. Furthermore, our formalism is general enough to cover the case of (vacuum) two-dimensional dilaton gravity. Therefore, besides reviewing Kucha\v{r}'s original work for Schwarzschild black holes from the framework of hyperbolic geometry, we present new results concerning the canonical reduction of Witten-black-hole geometrodynamics.Comment: Revtex, 35 pages, no figure

Generalized 2d dilaton gravity with matter fields

We extend the classical integrability of the CGHS model of 2d dilaton gravity [1] to a larger class of models, allowing the gravitational part of the action to depend more generally on the dilaton field and, simultaneously, adding fermion- and U(1)-gauge-fields to the scalar matter. On the other hand we provide the complete solution of the most general dilaton-dependent 2d gravity action coupled to chiral fermions. The latter analysis is generalized to a chiral fermion multiplet with a non-abelian gauge symmetry as well as to the (anti-)self-dual sector df = *df (df = -*df) of a scalar field f.Comment: 37 pages, Latex; typos and Eqs. (44,45) corrected; paragraph on p. 26, referring to a work of S. Solodukhin, reformulated; references adde

Classical and Quantum Gravity in 1+1 Dimensions, Part III: Solutions of Arbitrary Topology

All global solutions of arbitrary topology of the most general 1+1 dimensional dilaton gravity models are obtained. We show that for a generic model there are globally smooth solutions on any non-compact 2-surface. The solution space is parametrized explicitly and the geometrical significance of continuous and discrete labels is elucidated. As a corollary we gain insight into the (in general non-trivial) topology of the reduced phase space. The classification covers basically all 2D metrics of Lorentzian signature with a (local) Killing symmetry.Comment: 39 pages, 22 figures, uses AMSTeX, extended version of former chapter 7 (Gravitational Kinks) now available as gr-qc/9707053, problem with figure 6 fixe

String-Inspired Gravity Coupled to Yang-Mills Fields

String-inspired 1+1-dimensional gravity is coupled to Yang-Mills fields in the Cangemi-Jackiw gauge-theoretical formulation, based on the extended Poincar\'e group. A family of couplings, which involves metrics obtainable from the physical metric with a conformal rescaling, is considered, and the resulting family of models is investigated both at the classical and the quantum level. In particular, also using a series of Kirillov-Kostant phases, the wave functionals that solve the constraints are identified.Comment: 15 pages, LaTex