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'

Ispitivanja statičke kompresije i rezonantne vibracije celularnih materijala dobivenih gravitacijskim sinterovanjem šupljih brončanih kugli

The cylindrical and rod-shaped specimens were prepared by gravity sintering from Cu-Sn hollow spheres. On these samples, both static compression tests and measurements of resonance frequencies were performed. The compressive stress-strain curves revealed the features characteristic for a closed-cell ductile cellular solid. The removal of in general open porosity among loosely packed closed metallic hollow spheres was recognized as the principal mode of plastic deformation. The approximative effective moduli of elasticity were determined for cellular materials under consideration by means of the measurements of resonance frequencies on rod-shaped specimens.Cilindrični i šipkasti uzorci su pripremljeni gravitacionim sinterovanjem šupljih Cu-Sn kugli. Na tim uzorcima su provedena ispitivanja statičke kompresije i mjerenja rezonantnih frekvencija. Krivulja naprezanje-rastezanje nam pokazuje svojstva karakteristična za plastične celularne krute materijale sa zatvorenim ćelijama. Uklanjanje uglavnom otvorene povezanosti među labavo povezanim šupljim metalnim kuglama prepoznajemo kao glavni način plastične deformacije. Za celularne materijale koji se razmatraju određeni su približno učinkoviti moduli elastičnosti mjerenjem frekvencija rezonancije na šipkasto oblikovanim uzorcima

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.

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

Auswirkungen von Wärmebehandlungen von Mangan-Aluminium-Bronzen auf Gefüge und Korrosionsverhalten

Due to a much lower nickel content, manganese aluminum bronzes (MAB) are a cost-effective alternative to nickel aluminum bronzes (NAB). When the material is processed, different microstructures are observable in the material which have an impact on the corrosion resistance of MAB alloys. MAB samples were annealed at 900 °C and quenched in water. After that, annealing treatments at 600, 500, 400 and 300 °C for up to 24 h were performed and the samples were again quenched in water. Metallographic sections were prepared from all samples and potentiostatic corrosion tests at different potentials were performed in synthetic seawater. It was found that the sample annealed at 900 °C and quenched in water as well as those samples which underwent a second annealing treatment at low temperatures for shorter times exhibited a greater corrosion tendency than those undergoing a second annealing treatment at higher temperatures. X-ray diffraction measurements revealed that phase transformations and changes in grain size occurred during the annealing treatments. The increase in corrosion resistance as a result of annealing at higher temperatures is probably due to the strong intergrowth of the phases that are formed.Mangan-Aluminium-Bronze (MAB) ist aufgrund des viel geringeren Nickelgehalts eine kostengünstigere Alternative zu Nickel-Aluminium-Bronze (NAB). Bei der Werkstoffverarbeitung treten unterschiedliche Gefüge im Werkstoff auf, welche die Korrosionsbeständigkeit von MAB-Legierungen beeinflussen. MAB-Proben wurden bei 900 °C geglüht und in Wasser abgeschreckt. Danach wurden Glühungen bei 600, 500, 400 und 300 °C für bis zu 24 h durchgeführt und abermals in Wasser abgeschreckt. Von allen Proben wurden metallographische Schliffe angefertigt und potentiostatische Korrosionstests bei unterschiedlichen Potentialen, in künstlichem Meerwasser durchgeführt. Es wurde festgestellt, dass bei der bei 900 °C geglühten und abgeschreckten Probe, sowie jenen Proben die bei niedrigen Temperaturen und kürzeren Zeiten nachgeglüht wurden, eine stärkere Korrosionsneigung besteht, als bei den bei höheren Temperaturen nachgeglühten Proben. Röntgenbeugung-Messungen haben ergeben, dass es während der Temperungen zur Umwandlung von Phasen kommt und dabei auch die Korngrößen verändert werden. Die Erhöhung der Korrosionsbeständigkeit durch Tempern bei höheren Temperaturen ist vermutlich auf die starke Verwachsung der gebildeten Phasen zurückzuführen

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

Operando neutron imaging study of a commercial Li-ion battery at variable charge-discharge current densities

publishedVersio

The Feature Importance Ranking Measure

Most accurate predictions are typically obtained by learning machines with complex feature spaces (as e.g. induced by kernels). Unfortunately, such decision rules are hardly accessible to humans and cannot easily be used to gain insights about the application domain. Therefore, one often resorts to linear models in combination with variable selection, thereby sacrificing some predictive power for presumptive interpretability. Here, we introduce the Feature Importance Ranking Measure (FIRM), which by retrospective analysis of arbitrary learning machines allows to achieve both excellent predictive performance and superior interpretation. In contrast to standard raw feature weighting, FIRM takes the underlying correlation structure of the features into account. Thereby, it is able to discover the most relevant features, even if their appearance in the training data is entirely prevented by noise. The desirable properties of FIRM are investigated analytically and illustrated in simulations.Comment: 15 pages, 3 figures. to appear in the Proceedings of the European Conference on Machine Learning and Principles and Practice of Knowledge Discovery in Databases (ECML/PKDD), 200

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