Browsing by Author "Mueller, Peter"

We consider the Anderson model on the multi-dimensional cubic lattice and prove a positive lower bound on the density of states under certain conditions. For example, if the random variables are independently and identically distributed and the probability measure has a bounded Lebesgue density with compact support, and if this density is essentially bounded away from zero on its support, then we prove that the density of states is strictly positive for Lebesgue-almost every energy in the deterministic spectrum.

Glutamate is the major donor of nitrogen for anabolic reactions. The Gram-positive soil bacterium Bacillus subtilis either utilizes exogenously provided glutamate or synthesizes it using the gltAB-encoded glutamate synthase (GOGAT). In the absence of glutamate, the transcription factor GltC activates expression of the GOGAT genes for glutamate production. Consequently, a gltC mutant strain is auxotrophic for glutamate. Using a genetic selection and screening system, we could isolate and differentiate between gltC suppressor mutants in one step. All mutants had acquired the ability to synthesize glutamate, independent of GltC. We identified (i) gain-of-function mutations in the gltR gene, encoding the transcription factor GltR, (ii) mutations in the promoter of the gltAB operon and (iii) massive amplification of the genomic locus containing the gltAB operon. The mutants belonging to the first two classes constitutively expressed the gltAB genes and produced sufficient glutamate for growth. By contrast, mutants that belong to the third class appeared most frequently and solved glutamate limitation by increasing the copy number of the poorly expressed gltAB genes. Thus, glutamate auxotrophy of a B. subtilis gltC mutant can be relieved in multiple ways. Moreover, recombination-dependent amplification of the gltAB genes is the predominant mutational event indicating a hierarchy of mutations.

Objective The reduction of the frequency of rehospitalisation is important for improving the outcomes for patients with schizophrenia. Methods This study compares the rate of rehospitalisation between patients with antipsychotics in depot-from (n=77) and oral second-generation antipsychotics (SGA) (n=156). Results Patients with antipsychotics in depot-form had lower risk of rehospitalisation than with SGAs in oral-form after 24 months (p = 0.027) and 36 months (p = 0.018) (Kaplan-Meyer survival analysis, Log-Rank). Long intervals between two hospitalisations were found for flupentixol depot and clozapine. Conclusions Antipsychotics in depot-form require and active and close outpatient treatment, which may account for long intervals between hospitalisation improved outcomes for patients with schizophrenia.

We show persistence of both Anderson and dynamical localization in Schrodinger operators with non-positive (attractive) random decaying potential. We consider an Anderson-type Schrodinger operator with a non-positive ergodic random potential, and multiply the random potential by a decaying envelope function. If the envelope function decays slower than vertical bar x vertical bar(-2) at infinity, we prove that the operator has infinitely many eigenvalues below zero. For envelopes decaying as vertical bar x vertical bar(-alpha) at infinity, we determine the number of bound states below a given energy E<0, asymptotically as alpha down arrow 0. To show that bound states located at the bottom of the spectrum are related to the phenomenon of Anderson localization in the corresponding ergodic model, we prove: (a) these states are exponentially localized with a localization length that is uniform in the decay exponent alpha; (b) dynamical localization holds uniformly in alpha.

We investigate Laplacians on supercritical bond-percolation graphs with different boundary conditions at cluster borders. The integrated density of states of the Dirichlet Laplacian is found to exhibit a Lifshits tail at the lower spectral edge, while that of the Neumann Laplacian shows a van Hove asymptotics, which results from the percolating cluster. At the upper spectral edge, the behaviour is reversed. (C) 2007 Elsevier Inc. All rights reserved.

We study the ac-conductivity in linear response theory for the Anderson tight-binding model. We define the electrical ac-conductivity and calculate the linear-response current at zero temperature for arbitrary Fermi energy. In particular. the Fermi energy may, lie in a spectral region where extended states are believed to exist.

The iromycins A-D are members of a new family of rare alpha-pyridone metabolites. The isolation and structure elucidation of these microbial secondary metabolites from Streptomyces sp. Dra 17 revealed a N-heterocyclic core structure with two unusual side chains. Iromycins act as inhibitors of nitric oxide synthases (NOS), a protein family, which produces the crucial second messenger nitric oxide (NO). Importantly, these compounds inhibit selectively endothelial NOS rather than neuronal NOS and thus set prospects for both medical therapy and basic research. Feeding experiments with C-13- and N-15 -labeled precursors indicated an uncommon type of polyketide biosynthesis and clearly ruled out an isoprenoid origin. A detoxification pathway of a particular secondary metabolite in the host strain is a rare observation and here we demonstrate it with the iromycin family.

The threonine dehydratase IlvA is part of the isoleucine biosynthesis pathway in the Gram-positive model bacterium Bacillus subtilis. Consequently, deletion of ilvA causes isoleucine auxotrophy. It has been reported that ilvA pseudo-revertants having a derepressed hom-thrCB operon appear in the presence of threonine. Here we have characterized two classes of ilvA pseudo-revertants. In the first class the hom-thrCB operon was derepressed unmasking the threonine dehydratase activity of the threonine synthase ThrC. In the second class of mutants, threonine biosynthesis was more broadly affected. The first class of ilvA pseudo-revertants had a mutation in the P-hom promoter (P (hom)), resulting in constitutive expression of the hom-thrCB operon. In the second class of ilvA pseudo-revertants, the thrR gene encoding a putative DNA-binding protein was inactivated, also resulting in constitutive expression of the hom-thrCB operon. Here we demonstrate that ThrR is indeed a DNA-binding transcription factor that regulates the hom-thrCB operon and the thrD aspartokinase gene. DNA binding assays uncovered the DNA-binding site of ThrR and revealed that the repressor competes with the RNA polymerase for DNA binding. This study also revealed that ThrR orthologs are ubiquitous in genomes from the Gram-positive phylum Firmicutes and in some Gram-negative bacteria.

We provide an ergodic theorem for certain Banach-space valued functions on structures over Z(d), which allow for existence of frequencies of finite patterns. As an application we obtain existence of the integrated density of states for associated discrete finite-range operators in the sense of convergence of the distributions with respect to the supremum norm. These results apply to various examples including periodic operators, percolation models and nearest-neighbour hopping on the set of visible points. Our method gives explicit bounds on the speed of convergence in terms of the speed of convergence of the underlying frequencies. It uses neither von Neumann algebras nor a framework of random operators on a probability space.

Metals have vital roles in both the mechanism and architecture of biological macromolecules. Yet structures of metal-containing macromolecules in which metals are misidentified and/or suboptimally modeled are abundant in the Protein Data Bank (PDB). This shows the need for a diagnostic tool to identify and correct such modeling problems with metal-binding environments. The CheckMyMetal (CMM) web server (http://csgid.org/csgid/metal_sites/)is a sophisticated, user-friendly web-based method to evaluate metal-binding sites in macromolecular structures using parameters derived from 7,350 metal-binding sites observed in a benchmark data set of 2,304 high-resolution crystal structures. The protocol outlines how the CMM server can be used to detect geometric and other irregularities in the structures of metal-binding sites, as well as how it can alert researchers to potential errors in metal assignment. The protocol also gives practical guidelines for correcting problematic sites by modifying the metal-binding environment and/or redefining metal identity in the PDB file. Several examples where this has led to meaningful results are described in the ANTICIPATED RESULTS section. CMM was designed for a broad audience-biomedical researchers studying metal-containing proteins and nucleic acids-but it is equally well suited for structural biologists validating new structures during modeling or refinement. The CMM server takes the coordinates of a metal-containing macromolecule structure in the PDB format as input and responds within a few seconds for a typical protein structure with 2-5 metal sites and a few hundred amino acids.