Survey of Human Mitochondrial Diseases Using New Genomic/Proteomic Tools

BACKGROUND. We have constructed Bayesian prior-based, amino-acid sequence profiles for the complete yeast mitochondrial proteome and used them to develop methods for identifying and characterizing the context of protein mutations that give rise to human mitochondrial diseases. (Bayesian priors are conditional probabilities that allow the estimation of the likelihood of an event - such as an amino-acid substitution - on the basis of prior occurrences of similar events.) Because these profiles can assemble sets of taxonomically very diverse homologs, they enable identification of the structurally and/or functionally most critical sites in the proteins on the basis of the degree of sequence conservation. These profiles can also find distant homologs with determined three-dimensional structures that aid in the interpretation of effects of missense mutations. RESULTS. This survey reports such an analysis for 15 missense mutations one insertion and three deletions involved in Leber's hereditary optic neuropathy, Leigh syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Mohr-Tranebjaerg syndrome, iron-storage disorders related to Friedreich's ataxia, and hereditary spastic paraplegia. We present structural correlations for seven of the mutations. CONCLUSIONS. Of the 19 mutations analyzed, 14 involved changes in very highly conserved parts of the affected proteins. Five out of seven structural correlations provided reasonable explanations for the malfunctions. As additional genetic and structural data become available, this methodology can be extended. It has the potential for assisting in identifying new disease-related genes. Furthermore, profiles with structural homologs can generate mechanistic hypotheses concerning the underlying biochemical processes - and why they break down as a result of the mutations.United States Department of Energy (DE-FG02-98ER62558); National Science Foundation (DBI-9807993

Looking for a gift of Nature: Hadron loops and hybrid mixing

We investigate how coupling of valence q qbar to meson pairs can modify the properties of conventional q qbar and hybrid mesons. In a symmetry limit the mixing between hybrids and conventional q qbar with the same J^PC is shown to vanish. Flavor mixing between heavy and light q qbar due to meson loops is shown to be dual to the results of gluon mediated pQCD, and qualitatively different from mixing involving light flavors alone. The validity of the OZI rule for conventional q qbar and hybrid mesons is discussed.Comment: v2: added important references and discussion of previous literature; results and conclusions unchanged. 8 pages, 2 figure

Wear and Friction Modeling on Lifeboat Launch Systems

The RNLI provides search and rescue cover along the UK and RoI coast using a variety of lifeboats and launch techniques. In locations where there is no natural harbour it is necessary to use a slipway to launch the lifeboat into the sea. Lifeboat slipway stations consist of an initial section where the boat is held on rollers followed by an inclined keelway lined with low friction composite materials, the lifeboat is released from the top of the slipway and proceeds under its own weight into the water. The lifeboat is later recovered using a winch line. It is common to manually apply grease to the composite slipway lining before each launch and recovery in order to ensure sufficiently low friction for successful operation. With the introduction of the Tamar class lifeboat it is necessary to upgrade existing boathouses and standardise slipway operational procedures to ensure consistent operation. The higher contact pressures associated with the new lifeboat have led to issues of high friction and wear on the composite slipway linings and the manual application of grease to reduce friction is to be restricted due to environmental impact and cost factors. This paper presents a multidisciplinary approach to modelling slipway panel wear and friction using tribometer testing in conjunction with finite element analysis and slipway condition surveys to incorporate common real-world effects such as panel misalignments. Finally, it is shown that a freshwater lubrication system is effective, reducing cost and environmental impacts while maintaining good friction and wear performance

Isoprene Emission and Carbon Dioxide Protect Aspen Leaves from Heat Stress

High temperature, especially above 35oC, is known to reduce leaf photosynthetic rate in many tree species. This study investigated the effect of high temperature on isoprene-emitting (aspen) and non- emitting (birch) trees under ambient and elevated CO2 under open field conditions. Aspen trees tolerate heat better than birch trees and elevated CO2 protects both species against moderate heat stress. The increased thermotolerance in aspen trees compared to the birch trees may result from the aspen's ability to produce isoprene. Elevated CO2 increased carboxylation capacity, photosynthetic electron transport capacity and triose phosphate use in both birch and aspen trees. High temperature decreased all of these parameters in birch regardless of CO2 treatment but only photosynthetic electron transport and triose phosphate use at ambient CO2 were reduced in aspen. As temperature rises, non-isoprene-emitting trees will be at a disadvantage and biological diversity and species richness might be lost in some ecosystems. Our results indicate that isoprene emitting tree species will have an advantage over non-isoprene emitting ones under high temperatures

The Raman Spectrum of Boron Trifluoride Gas

The Raman spectrum of BF3 was photographed using a purified preparation obtained from the thermal decomposition of C6H5N2BF4. Of the lines observed, that with the frequency 888 cm^—1 is certainly, and the band at 439–513 cm^—1 is probably due to BF3. The Raman frequencies and the infra-red results of Bailey et al. are assigned to the fundamental modes of vibrations

Assumptions that imply quantum dynamics is linear

A basic linearity of quantum dynamics, that density matrices are mapped linearly to density matrices, is proved very simply for a system that does not interact with anything else. It is assumed that at each time the physical quantities and states are described by the usual linear structures of quantum mechanics. Beyond that, the proof assumes only that the dynamics does not depend on anything outside the system but must allow the system to be described as part of a larger system. The basic linearity is linked with previously established results to complete a simple derivation of the linear Schrodinger equation. For this it is assumed that density matrices are mapped one-to-one onto density matrices. An alternative is to assume that pure states are mapped one-to-one onto pure states and that entropy does not decrease.Comment: 10 pages. Added references. Improved discussion of equations of motion for mean values. Expanded Introductio

Dark Matter Annihilation Signatures from Electroweak Bremsstrahlung

We examine observational signatures of dark matter annihilation in the Milky Way arising from electroweak bremsstrahlung contributions to the annihilation cross section. It has been known for some time that photon bremsstrahlung may significantly boost DM annihilation yields. Recently, we have shown that electroweak bremsstrahlung of W and Z gauge bosons can be the dominant annihilation channel in some popular models with helicity-suppressed 2 --> 2 annihilation. W/Z-bremsstrahlung is particularly interesting because the gauge bosons produced via annihilation subsequently decay to produce large correlated fluxes of electrons, positrons, neutrinos, hadrons (including antiprotons) and gamma rays, which are all of importance in indirect dark matter searches. Here we calculate the spectra of stable annihilation products produced via gamma/W/Z-bremsstrahlung. After modifying the fluxes to account for the propagation through the Galaxy, we set upper bounds on the annihilation cross section via a comparison with observational data. We show that stringent cosmic ray antiproton limits preclude a sizable dark matter contribution to observed cosmic ray positron fluxes in the class of models for which the bremsstrahlung processes dominate.Comment: 11 pages, 6 figures. Updated to match PRD versio

The long-term outcome of treated high-risk nonmuscle-invasive bladder cancer

This article is available open access through the publisher’s website from the link below. Copyright © 2012 American Cancer Society.BACKGROUND: The treatment of high-risk nonmuscle-invasive bladder cancer (NMIBC) is difficult given its unpredictable natural history and patient comorbidities. Because current case series are mostly limited in size, the authors report the outcomes from a large, single-center series. METHODS: The authors reviewed all patients with primary, high-risk NMIBC at their institution from 1994 to 2010. Outcomes were matched with clinicopathologic data. Patients who had muscle invasion within 6 months or had insufficient follow-up (<6 months) were excluded. Correlations were analyzed using multivariable Cox regression and log-rank analysis (2-sided; P < .05). RESULTS: In total, 712 patients (median age, 73.7 years) were included. Progression to muscle invasion occurred in 110 patients (15.8%; 95% confidence interval [CI], 13%-18.3%) at a median of 17.2 months (interquartile range, 8.9-35.8 months), including 26.5% (95% CI, 22.2%-31.3%) of the 366 patients who had >5 years follow-up. Progression was associated with age (hazard ratio [HR], 1.04; P = .007), dysplastic urothelium (HR, 1.6; P = .003), urothelial cell carcinoma variants (HR, 3.2; P = .001), and recurrence (HR, 18.3; P .6). CONCLUSIONS: Within a program of conservative treatment, progression of high-risk NMIBC was associated with a poor prognosis. Surveillance and bacillus Calmette-Guerin were ineffective in altering the natural history of this disease. The authors concluded that the time has come to rethink the paradigm of management of this disease.GlaxoSmithKline, Yorkshire Cancer Research, Sheffield Hospitals Charitable Trust, Astellas Educational Foundation, and the European Union

Extreme Ultraviolet Emission in the Fornax Cluster of Galaxies

We present studies of the Extreme Ultraviolet (EUV) emission in the Fornax cluster of galaxies; a relatively nearby well-studied cluster with X-ray emitting cluster gas and a very large radio source. We examine both the large-scale (~size of the X-ray emitting cluster gas), and the small-scale (<arcmin) emission. We find that this cluster has large-scale diffuse EUV emission. However, at the sensitivity level of the existing EUVE data, this emission is due entirely to the low energy tail of the X-ray emitting gas. We have also examined small-scale structures in raw EUVE images of this cluster. We find that small-scale irregularities are present in all raw Deep Survey images as a result of small-scale detector effects. These effects can be removed by appropriate flat-fielding. After flat-fielding, the Fornax cluster still shows a few significant regions of small-scale EUV enhancement. We find that these are emission from stars and galaxies in the field. We find that at existing levels of sensitivity, there is no excess EUV emission in the cluster on either large or small scales.Comment: 6 pages, 3 eps figures, aastex5, Accepted to ApJ