Large-scale albuminuria screen for nephropathy models in chemically induced mouse mutants

Background/Aim: Phenotype-driven screening of a great pool of randomly mutant mice and subsequent selection of animals showing symptoms equivalent to human kidney diseases may result in the generation of novel suitable models for the study of the pathomechanisms and the identification of genes involved in kidney dysfunction. Methods: We carried out a large-scale analysis of ethylnitrosourea (ENU)-induced mouse mutants for albuminuria by using qualitative SDS-polyacrylamide gel electrophoresis. Results: The primary albuminuria screen preceded the comprehensive phenotypic mutation analysis in a part of the mice of the Munich ENU project to avoid loss of mutant animals as a consequence of prolonged suffering from severe nephropathy. The primary screen detected six confirmed phenotypic variants in 2,011 G1 animals screened for dominant mutations and no variant in 48 G3 pedigrees screened for recessive mutations. Further breeding experiments resulted in two lines showing a low phenotypic penetrance of albuminuria. The secondary albuminuria screen was carried out in mutant lines which were established in the Munich ENU project without preceding primary albuminuria analysis. Two lines showing increased plasma urea levels were chosen to clarify if severe kidney lesions are involved in the abnormal phenotype. This analysis revealed severe albuminuria in mice which are affected by a recessive mutation leading to increased plasma urea and cholesterol levels. Conclusion: Thus, the phenotypic selection of ENU-induced mutants according to the parameter proteinuria in principle demonstrates the feasibility to identify nephropathy phenotypes in ENU-mutagenized mice. Copyright (C) 2005 S. Karger AG, Basel

Disorder Potentials near Lithographically Fabricated Atom Chips

We show that previously observed large disorder potentials in magnetic microtraps for neutral atoms are reduced by about two orders of magnitude when using atom chips with lithographically fabricated high quality gold layers. Using one dimensional Bose-Einstein condensates, we probe the remaining magnetic field variations at surface distances down to a few microns. Measurements on a 100 um wide wire imply that residual variations of the current flow result from local properties of the wire.Comment: submitted on September 24th, 200

volumetric characterisation and correlation to established classification systems

Objective and sensitive assessment of cartilage repair outcomes lacks suitable methods. This study investigated the feasibility of 3D ultrasound biomicroscopy (UBM) to quantify cartilage repair outcomes volumetrically and their correlation with established classification systems. 32 sheep underwent bilateral treatment of a focal cartilage defect. One or two years post- operatively the repair outcomes were assessed and scored macroscopically (Outerbridge, ICRS-CRA), by magnetic resonance imaging (MRI, MOCART), and histopathology (O'Driscoll, ICRS-I and ICRS-II). The UBM data were acquired after MRI and used to reconstruct the shape of the initial cartilage layer, enabling the estimation of the initial cartilage thickness and defect volume as well as volumetric parameters for defect filling, repair tissue, bone loss and bone overgrowth. The quantification of the repair outcomes revealed high variations in the initial thickness of the cartilage layer, indicating the need for cartilage thickness estimation before creating a defect. Furthermore, highly significant correlations were found for the defect filling estimated from UBM to the established classification systems. 3D visualisation of the repair regions showed highly variable morphology within single samples. This raises the question as to whether macroscopic, MRI and histopathological scoring provide sufficient reliability. The biases of the individual methods will be discussed within this context. UBM was shown to be a feasible tool to evaluate cartilage repair outcomes, whereby the most important objective parameter is the defect filling. Translation of UBM into arthroscopic or transcutaneous ultrasound examinations would allow non-destructive and objective follow-up of individual patients and better comparison between the results of clinical trials

Cluster density functional theory for lattice models based on the theory of Mobius functions

Rosenfeld's fundamental measure theory for lattice models is given a rigorous formulation in terms of the theory of Mobius functions of partially ordered sets. The free-energy density functional is expressed as an expansion in a finite set of lattice clusters. This set is endowed a partial order, so that the coefficients of the cluster expansion are connected to its Mobius function. Because of this, it is rigorously proven that a unique such expansion exists for any lattice model. The low-density analysis of the free-energy functional motivates a redefinition of the basic clusters (zero-dimensional cavities) which guarantees a correct zero-density limit of the pair and triplet direct correlation functions. This new definition extends Rosenfeld's theory to lattice model with any kind of short-range interaction (repulsive or attractive, hard or soft, one- or multi-component...). Finally, a proof is given that these functionals have a consistent dimensional reduction, i.e. the functional for dimension d' can be obtained from that for dimension d (d'<d) if the latter is evaluated at a density profile confined to a d'-dimensional subset.Comment: 21 pages, 2 figures, uses iopart.cls, as well as diagrams.sty (included

Quantum Hall transitions: An exact theory based on conformal restriction

We revisit the problem of the plateau transition in the integer quantum Hall effect. Here we develop an analytical approach for this transition, based on the theory of conformal restriction. This is a mathematical theory that was recently developed within the context of the Schramm-Loewner evolution which describes the stochastic geometry of fractal curves and other stochastic geometrical fractal objects in 2D space. Observables elucidating the connection with the plateau transition include the so-called point-contact conductances (PCCs) between points on the boundary of the sample, described within the language of the Chalker-Coddington network model. We show that the disorder-averaged PCCs are characterized by classical probabilities for certain geometric objects in the plane (pictures), occurring with positive statistical weights, that satisfy the crucial restriction property with respect to changes in the shape of the sample with absorbing boundaries. Upon combining this restriction property with the expected conformal invariance at the transition point, we employ the mathematical theory of conformal restriction measures to relate the disorder-averaged PCCs to correlation functions of primary operators in a conformal field theory (of central charge $c=0$). We show how this can be used to calculate these functions in a number of geometries with various boundary conditions. Since our results employ only the conformal restriction property, they are equally applicable to a number of other critical disordered electronic systems in 2D. For most of these systems, we also predict exact values of critical exponents related to the spatial behavior of various disorder-averaged PCCs.Comment: Published versio

Radiofrequency antenna concepts for human cardiac MR at 14.0 T

OBJECTIVE: To examine the feasibility of human cardiac MR (CMR) at 14.0 T using high-density radiofrequency (RF) dipole transceiver arrays in conjunction with static and dynamic parallel transmission (pTx). MATERIALS AND METHODS: RF arrays comprised of self-grounded bow-tie (SGBT) antennas, bow-tie (BT) antennas, or fractionated dipole (FD) antennas were used in this simulation study. Static and dynamic pTx were applied to enhance transmission field (B(1)(+)) uniformity and efficiency in the heart of the human voxel model. B(1)(+) distribution and maximum specific absorption rate averaged over 10 g tissue (SAR(10g)) were examined at 7.0 T and 14.0 T. RESULTS: At 14.0 T static pTx revealed a minimum B(1)(+)(ROI) efficiency of 0.91 μT/√kW (SGBT), 0.73 μT/√kW (BT), and 0.56 μT/√kW (FD) and maximum SAR(10g) of 4.24 W/kg, 1.45 W/kg, and 2.04 W/kg. Dynamic pTx with 8 kT points indicate a balance between B(1)(+)(ROI) homogeneity (coefficient of variation  1.11 µT/√kW) at 14.0 T with a maximum SAR(10g) < 5.25 W/kg. DISCUSSION: MRI of the human heart at 14.0 T is feasible from an electrodynamic and theoretical standpoint, provided that multi-channel high-density antennas are arranged accordingly. These findings provide a technical foundation for further explorations into CMR at 14.0 T

Future directions for the management of pain in osteoarthritis.

Osteoarthritis (OA) is the predominant form of arthritis worldwide, resulting in a high degree of functional impairment and reduced quality of life owing to chronic pain. To date, there are no treatments that are known to modify disease progression of OA in the long term. Current treatments are largely based on the modulation of pain, including NSAIDs, opiates and, more recently, centrally acting pharmacotherapies to avert pain. This review will focus on the rationale for new avenues in pain modulation, including inhibition with anti-NGF antibodies and centrally acting analgesics. The authors also consider the potential for structure modification in cartilage/bone using growth factors and stem cell therapies. The possible mismatch between structural change and pain perception will also be discussed, introducing recent techniques that may assist in improved patient phenotyping of pain subsets in OA. Such developments could help further stratify subgroups and treatments for people with OA in future

Cumulants and the moment algebra: tools for analysing weak measurements

Recently it has been shown that cumulants significantly simplify the analysis of multipartite weak measurements. Here we consider the mathematical structure that underlies this, and find that it can be formulated in terms of what we call the moment algebra. Apart from resulting in simpler proofs, the flexibility of this structure allows generalizations of the original results to a number of weak measurement scenarios, including one where the weakly interacting pointers reach thermal equilibrium with the probed system.Comment: Journal reference added, minor correction

Fast Evaluation of Interlace Polynomials on Graphs of Bounded Treewidth

We consider the multivariate interlace polynomial introduced by Courcelle (2008), which generalizes several interlace polynomials defined by Arratia, Bollobas, and Sorkin (2004) and by Aigner and van der Holst (2004). We present an algorithm to evaluate the multivariate interlace polynomial of a graph with n vertices given a tree decomposition of the graph of width k. The best previously known result (Courcelle 2008) employs a general logical framework and leads to an algorithm with running time f(k)*n, where f(k) is doubly exponential in k. Analyzing the GF(2)-rank of adjacency matrices in the context of tree decompositions, we give a faster and more direct algorithm. Our algorithm uses 2^{3k^2+O(k)}*n arithmetic operations and can be efficiently implemented in parallel.Comment: v4: Minor error in Lemma 5.5 fixed, Section 6.6 added, minor improvements. 44 pages, 14 figure

Searching for network modules

When analyzing complex networks a key target is to uncover their modular structure, which means searching for a family of modules, namely node subsets spanning each a subnetwork more densely connected than the average. This work proposes a novel type of objective function for graph clustering, in the form of a multilinear polynomial whose coefficients are determined by network topology. It may be thought of as a potential function, to be maximized, taking its values on fuzzy clusterings or families of fuzzy subsets of nodes over which every node distributes a unit membership. When suitably parametrized, this potential is shown to attain its maximum when every node concentrates its all unit membership on some module. The output thus is a partition, while the original discrete optimization problem is turned into a continuous version allowing to conceive alternative search strategies. The instance of the problem being a pseudo-Boolean function assigning real-valued cluster scores to node subsets, modularity maximization is employed to exemplify a so-called quadratic form, in that the scores of singletons and pairs also fully determine the scores of larger clusters, while the resulting multilinear polynomial potential function has degree 2. After considering further quadratic instances, different from modularity and obtained by interpreting network topology in alternative manners, a greedy local-search strategy for the continuous framework is analytically compared with an existing greedy agglomerative procedure for the discrete case. Overlapping is finally discussed in terms of multiple runs, i.e. several local searches with different initializations.Comment: 10 page