126 research outputs found
Small eigenvalues of the SU(3) Dirac operator on the lattice and in Random Matrix Theory
We have calculated complete spectra of the staggered Dirac operator on the
lattice in quenched SU(3) gauge theory for \beta = 5.4 and various lattice
sizes. The microscopic spectral density, the distribution of the smallest
eigenvalue, and the two-point spectral correlation function are analyzed. We
find the expected agreement of the lattice data with universal predictions of
the chiral unitary ensemble of random matrix theory up to a certain energy
scale, the Thouless energy. The deviations from the universal predictions are
determined using the disconnected scalar susceptibility. We find that the
Thouless energy scales with the lattice size as expected from theoretical
arguments making use of the Gell-Mann--Oakes--Renner relation.Comment: REVTeX, 5 pages, 4 figure
Statistical analysis and the equivalent of a Thouless energy in lattice QCD Dirac spectra
Random Matrix Theory (RMT) is a powerful statistical tool to model spectral
fluctuations. This approach has also found fruitful application in Quantum
Chromodynamics (QCD). Importantly, RMT provides very efficient means to
separate different scales in the spectral fluctuations. We try to identify the
equivalent of a Thouless energy in complete spectra of the QCD Dirac operator
for staggered fermions from SU(2) lattice gauge theory for different lattice
size and gauge couplings. In disordered systems, the Thouless energy sets the
universal scale for which RMT applies. This relates to recent theoretical
studies which suggest a strong analogy between QCD and disordered systems. The
wealth of data allows us to analyze several statistical measures in the bulk of
the spectrum with high quality. We find deviations which allows us to give an
estimate for this universal scale. Other deviations than these are seen whose
possible origin is discussed. Moreover, we work out higher order correlators as
well, in particular three--point correlation functions.Comment: 24 pages, 24 figures, all included except one figure, missing eps
file available at http://pluto.mpi-hd.mpg.de/~wilke/diff3.eps.gz, revised
version, to appear in PRD, minor modifications and corrected typos, Fig.4
revise
Predicting evolution and visualizing high-dimensional fitness landscapes
The tempo and mode of an adaptive process is strongly determined by the
structure of the fitness landscape that underlies it. In order to be able to
predict evolutionary outcomes (even on the short term), we must know more about
the nature of realistic fitness landscapes than we do today. For example, in
order to know whether evolution is predominantly taking paths that move upwards
in fitness and along neutral ridges, or else entails a significant number of
valley crossings, we need to be able to visualize these landscapes: we must
determine whether there are peaks in the landscape, where these peaks are
located with respect to one another, and whether evolutionary paths can connect
them. This is a difficult task because genetic fitness landscapes (as opposed
to those based on traits) are high-dimensional, and tools for visualizing such
landscapes are lacking. In this contribution, we focus on the predictability of
evolution on rugged genetic fitness landscapes, and determine that peaks in
such landscapes are highly clustered: high peaks are predominantly close to
other high peaks. As a consequence, the valleys separating such peaks are
shallow and narrow, such that evolutionary trajectories towards the highest
peak in the landscape can be achieved via a series of valley crossingsComment: 12 pages, 7 figures. To appear in "Recent Advances in the Theory and
Application of Fitness Landscapes" (A. Engelbrecht and H. Richter, eds.).
Springer Series in Emergence, Complexity, and Computation, 201
Ab initio Quantum and ab initio Molecular Dynamics of the Dissociative Adsorption of Hydrogen on Pd(100)
The dissociative adsorption of hydrogen on Pd(100) has been studied by ab
initio quantum dynamics and ab initio molecular dynamics calculations. Treating
all hydrogen degrees of freedom as dynamical coordinates implies a high
dimensionality and requires statistical averages over thousands of
trajectories. An efficient and accurate treatment of such extensive statistics
is achieved in two steps: In a first step we evaluate the ab initio potential
energy surface (PES) and determine an analytical representation. Then, in an
independent second step dynamical calculations are performed on the analytical
representation of the PES. Thus the dissociation dynamics is investigated
without any crucial assumption except for the Born-Oppenheimer approximation
which is anyhow employed when density-functional theory calculations are
performed. The ab initio molecular dynamics is compared to detailed quantum
dynamical calculations on exactly the same ab initio PES. The occurence of
quantum oscillations in the sticking probability as a function of kinetic
energy is addressed. They turn out to be very sensitive to the symmetry of the
initial conditions. At low kinetic energies sticking is dominated by the
steering effect which is illustrated using classical trajectories. The steering
effects depends on the kinetic energy, but not on the mass of the molecules.
Zero-point effects lead to strong differences between quantum and classical
calculations of the sticking probability. The dependence of the sticking
probability on the angle of incidence is analysed; it is found to be in good
agreement with experimental data. The results show that the determination of
the potential energy surface combined with high-dimensional dynamical
calculations, in which all relevant degrees of freedon are taken into account,
leads to a detailed understanding of the dissociation dynamics of hydrogen at a
transition metal surface.Comment: 15 pages, 9 figures, subm. to Phys. Rev.
Meta-analysis of type 2 Diabetes in African Americans Consortium
Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR) = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe
Heterogeneous clinical phenotypes and cerebral malformations reflected by rotatin cellular dynamics
Recessive mutations in RTTN, encoding the protein rotatin, were originally identified as cause of polymicrogyria, a cortical malformation. With time, a wide variety of other brain malformations has been ascribed to RTTN mutations, including primary microcephaly. Rotatin is a centrosomal protein possibly involved in centriolar elongation and ciliogenesis. However, the function of rotatin in brain development is largely unknown and the molecular disease mechanism underlying cortical malformations has not yet been elucidated. We performed both clinical and cell biological studies, aimed at clarifying rotatin function and pathogenesis. Review of the 23 published and five unpublished clinical cases and genomic mutations, including the effect of novel deep intronic pathogenic mutations on RTTN transcripts, allowed us to extrapolate the core phenotype, consisting of intellectual disability, short stature, microcephaly, lissencephaly, periventricular heterotopia, polymicrogyria and other malformations. We show that the severity of the phenotype is related to residual function of the protein, not only the level of mRNA expression. Skin fibroblasts from eight affected individuals were studied by high resolution immunomicroscopy and flow cytometry, in parallel with in vitro expression of RTTN in HEK293T cells. We demonstrate that rotatin regulates different phases of the cell cycle and is mislocalized in affected individuals. Mutant cells showed consistent and severe mitotic failure with centrosome amplification and multipolar spindle formation, leading to aneuploidy and apoptosis, which could relate to depletion of neuronal progenitors often observed in microcephaly. We confirmed the role of rotatin in functional and structural maintenance of primary cilia and determined that the protein localized not only to the basal body, but also to the axoneme, proving the functional interconnectivity between ciliogenesis and cell cycle progression. Proteomics analysis of both native and exogenous rotatin uncovered that rotatin interacts with the neuronal (non-muscle) myosin heavy chain subunits, motors of nucleokinesis during neuronal migration, and in human induced pluripotent stem cell-derived bipolar mature neurons rotatin localizes at the centrosome in the leading edge. This illustrates the role of rotatin in neuronal migration. These different functions of rotatin explain why RTTN mutations can lead to heterogeneous cerebral malformations, both related to proliferation and migration defects.Genetics of disease, diagnosis and treatmen
- …