Proteomics of Cytochrome c Oxidase-Negative versus -Positive Muscle Fiber Sections in Mitochondrial Myopathy

The mosaic distribution of cytochrome c oxidase(+) (COX+) and COX - muscle fibers in mitochondrial disorders allows the sampling of fibers with compensated and decompensated mitochondrial function from the same individual. We apply laser capture microdissection to excise individual COX+ and COX- fibers from the biopsies of mitochondrial myopathy patients. Using mass spectrometry-based proteomics, we quantify >4,000 proteins per patient. While COX+ fibers show a higher expression of respiratory chain components, COX- fibers display protean adaptive responses, including upregulation of mitochondrial ribosomes, translation proteins, and chaperones. Upregulated proteins include C1QBP, required for mitoribosome formation and protein synthesis, and STOML2, which organizes cardiolipin-enriched microdomains and the assembly of respiratory supercomplexes. Factoring in fast/slow fiber type, COX (-) slow fibers show a compensatory upregulation of beta-oxidation, the AAA(+) protease AFG3L1, and the OPA1-dependent cristae remodeling program. These findings reveal compensatory mechanisms in muscle fibers struggling with energy shortage and metabolic stress

Strengths and Weaknesses of Parallel Tempering

Parallel tempering, also known as replica exchange Monte Carlo, is studied in the context of two simple free energy landscapes. The first is a double well potential defined by two macrostates separated by a barrier. The second is a `golf course' potential defined by microstates having two possible energies with exponentially more high energy states than low energy states. The equilibration time for replica exchange is analyzed for both systems. For the double well system, parallel tempering with a number of replicas that scales as the square root of the barrier height yields exponential speedup of the equilibration time. On the other hand, replica exchange yields only marginal speed-up for the golf course system. For the double well system, the free energy difference between the two wells has a large effect on the equilibration time. Nearly degenerate wells equilibrate much more slowly than strongly asymmetric wells. It is proposed that this difference in equilibration time may lead to a bias in measuring overlaps in spin glasses. These examples illustrate the strengths and weaknesses of replica exchange and may serve as a guide for understanding and improving the method in various applications.Comment: 18 pages, 4 figures. v2: typos fixed and wording changes to improve clarit

Oxidation and crystallization of an amorphous Zr60Al15Ni25 alloy

The amorphous ternary metallic alloy Zr60Al15Ni25 was oxidized in dry oxygen in the temperature range 310 ±C to 410 ±C. Rutherford backscattering (RBS) and cross-sectional transmission electron microscopy (TEM) studies suggest that during this treatment an amorphous layer of zirconium-aluminum-oxide is formed at the surface. Nickel was depleted in the oxide and enriched in the amorphous alloy near the interface. The oxide layer thickness grows parabolically with annealing duration, with a transport constant of 2.8 x 10^-5 m^2/s x exp(-1.7 eV/kT). The oxidation rate may be controlled by the diffusion of Ni in the amorphous alloy. At later stages of the oxidation process, precipitates of nanocrystalline ZrO2 appear in the oxide near the interface. Finally, two intermetallic phases nucleate and grow simultaneously in the alloy, one at the interface and one within the alloy. An explanation involving preferential oxidation is proposed

Superfield extended BRST quantization in general coordinates

We propose a superfield formalism of Lagrangian BRST-antiBRST quantization of arbitrary gauge theories in general coordinates with the base manifold of fields and antifields desribed in terms of both bosonic and fermionic variables.Comment: LaTex, 10 page

Quantum properties of general gauge theories with composite and external fields

The generating functionals of Green's functions with composite and external fields are considered in the framework of BV and BLT quantization methods for general gauge theories. The corresponding Ward identities are derived and the gauge dependence is investigatedComment: 24 pages, LATEX, slightly changed to clarify the essential new aspect concerning composite fields depending on external ones; added formulas showing lack of (generalized) nilpotence of operators appearing in the Ward identitie

Hail potential in Europe based on a regional climate model hindcast

comprehensive, reliable, and consistent information about hail frequency and intensity in Europe is not available. To overcome this constraint, we developed a logistic hail model that quantifies the potential of the atmosphere to form hailstorms. The model is based on a combination of appropriate hail-relevant meteorological parameters. This paper presents the application of an adjusted version of the logistic model with the objective being to estimate the hail potential across Europe based on dynamically downscaled National Centers for Environmental Prediction/National Center for Atmospheric Research1 reanalysis over a long-term period of 60 years (1951–2010). The model output, in terms of the potential hail index (PHI), identified several hot spots that are well known from other observational studies. Time series of the PHI over the 60 year period show a high correlation at different sites across Europe and high annual and multiannual variability, but no overall trend

Dynamical stabilization of classical multi electron targets against autoionization

We demonstrate that a recently published quasiclassical M\oller type approach [Geyer and Rost 2002, J. Phys. B 35 1479] can be used to overcome the problem of autoionization, which arises in classical trajectory calculations for many electron targets. In this method the target is stabilized dynamically by a backward--forward propagation scheme. We illustrate this refocusing and present total cross sections for single and double ionization of helium by electron impact.Comment: LaTeX, 6 pages, 2 figures; submitted to J. Phys.

Biophysically motivated efficient estimation of the spatially isotropic R*2 component from a single gradient‐recalled echo measurement

Purpose To propose and validate an efficient method, based on a biophysically motivated signal model, for removing the orientation‐dependent part of R*2 using a single gradient‐recalled echo (GRE) measurement. Methods The proposed method utilized a temporal second‐order approximation of the hollow‐cylinder‐fiber model, in which the parameter describing the linear signal decay corresponded to the orientation‐independent part of R*2. The estimated parameters were compared to the classical, mono‐exponential decay model for R*2 in a sample of an ex vivo human optic chiasm (OC). The OC was measured at 16 distinct orientations relative to the external magnetic field using GRE at 7T. To show that the proposed signal model can remove the orientation dependence of R*2, it was compared to the established phenomenological method for separating R*2 into orientation‐dependent and ‐independent parts. Results Using the phenomenological method on the classical signal model, the well‐known separation of R*2 into orientation‐dependent and ‐independent parts was verified. For the proposed model, no significant orientation dependence in the linear signal decay parameter was observed. Conclusions Since the proposed second‐order model features orientation‐dependent and ‐independent components at distinct temporal orders, it can be used to remove the orientation dependence of R*2 using only a single GRE measurement