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

Trying to define Free Will : a cognitive and fonctional model proposal

The debate about Free Will has been in the human mind for centuries, but has become even more intense with the recent scientific findings adding new lights on the problem. This interdisciplinary explosion of interest for the topic has brought many insightful knowledge, but also a great deal of epistemological problems. We think that those epistemological problems are deeply related to the very definition of Free Will and how this definition interacts with the interpretations of experimental results. We will thus outline a few of these problems and then propose a definition of Free Will which takes into account those epistemological pitfalls

QED self-energy contribution to highly-excited atomic states

We present numerical values for the self-energy shifts predicted by QED (Quantum Electrodynamics) for hydrogenlike ions (nuclear charge $60 \le Z \le 110$) with an electron in an $n=3$, 4 or 5 level with high angular momentum ($5/2\le j \le 9/2$). Applications include predictions of precision transition energies and studies of the outer-shell structure of atoms and ions.Comment: 20 pages, 5 figure

Lamb Shift of 3P and 4P states and the determination of α\alpha

The fine structure interval of P states in hydrogenlike systems can be determined theoretically with high precision, because the energy levels of P states are only slightly influenced by the structure of the nucleus. Therefore a measurement of the fine structure may serve as an excellent test of QED in bound systems or alternatively as a means of determining the fine structure constant $\alpha$ with very high precision. In this paper an improved analytic calculation of higher-order binding corrections to the one-loop self energy of 3P and 4P states in hydrogen-like systems with low nuclear charge number $Z$ is presented. A comparison of the analytic results to the extrapolated numerical data for high $Z$ ions serves as an independent test of the analytic evaluation. New theoretical values for the Lamb shift of the P states and for the fine structure splittings are given.Comment: 33 pages, LaTeX, 4 tables, 4 figure

Benchmark on neutron capture extracted from (d,p)(d,p) reactions

Direct neutron capture reactions play an important role in nuclear astrophysics and applied physics. Since for most unstable short-lived nuclei it is not possible to measure the $(n, \gamma)$ cross sections, $(d,p)$ reactions have been used as an alternative indirect tool. We analyze simultaneously $^{48}{\rm Ca}(d,p)^{49}{\rm Ca}$ at deuteron energies $2, 13, 19$ and 56 MeV and the thermal $(n,\gamma)$ reaction at 25 meV. We include results for the ground state and the first excited state of $^{49}$Ca. From the low-energy $(d,p)$ reaction, the neutron asymptotic normalization coefficient (ANC) is determined. Using this ANC, we extract the spectroscopic factor (SF) from the higher energy $(d,p)$ data and the $(n, \gamma)$ data. The SF obtained through the 56 MeV $(d,p)$ data are less accurate but consistent with those from the thermal capture. We show that to have a similar dependence on the single particle parameters as in the $(n, \gamma)$, the (d,p) reaction should be measured at 30 MeV.Comment: 5 pg, 4 figs, Phys. Rev. C (rapid) in pres

Dust absorption and scattering in the silicon K-edge

The composition and properties of interstellar silicate dust are not well understood. In X-rays, interstellar dust can be studied in detail by making use of the fine structure features in the Si K-edge. The features in the Si K-edge offer a range of possibilities to study silicon-bearing dust, such as investigating the crystallinity, abundance, and the chemical composition along a given line of sight. We present newly acquired laboratory measurements of the silicon K-edge of several silicate-compounds that complement our measurements from our earlier pilot study. The resulting dust extinction profiles serve as templates for the interstellar extinction that we observe. The extinction profiles were used to model the interstellar dust in the dense environments of the Galaxy. The laboratory measurements, taken at the Soleil synchrotron facility in Paris, were adapted for astrophysical data analysis and implemented in the SPEX spectral fitting program. The models were used to fit the spectra of nine low-mass X-ray binaries located in the Galactic center neighborhood in order to determine the dust properties along those lines of sight. Most lines of sight can be fit well by amorphous olivine. We also established upper limits on the amount of crystalline material that the modeling allows. We obtained values of the total silicon abundance, silicon dust abundance, and depletion along each of the sightlines. We find a possible gradient of $0.06\pm0.02$ dex/kpc for the total silicon abundance versus the Galactocentric distance. We do not find a relation between the depletion and the extinction along the line of sight.Comment: 18 pages, 16 figures. Accepted for publication in Astronomy and Astrophysic

Outer Regions of the Cluster Gaseous Atmospheres

We present a systematic study of the hot gas distribution in the outer regions of regular clusters using ROSAT PSPC data. Outside the cooling flow region, the beta-model describes the observed surface brightness closely, but not precisely. Between 0.3 and 1 virial radii, the profiles are characterized by a power law with slope, expressed in terms of the beta parameter, in the range beta=0.65 to 0.85. The values of beta in this range of radii are typically larger by ~0.05 than those derived from the global fit. There is a mild trend for the slope to increase with temperature, from ~0.68 for 3 keV clusters to ~0.8 for 10 keV clusters; however, even at high temperatures there are clusters with flat gas profiles, 0.7. Our values of beta at large radius are systematically higher, and the trend of beta with temperature is weaker than was previously found; the most likely explanation is that earlier studies were affected by an incomplete exclusion of the central cooling flow regions. For our regular clusters, the gas distribution at large radii is quite close to spherically symmetric and this is shown not to be an artifact of the sample selection. The gas density profiles are very similar when compared in the units of cluster virial radius. The radius of fixed mean gas overdensity 1000 (corresponding to the dark matter overdensity 200 for Omega=0.2) shows a tight correlation with temperature, R~T**0.5, as expected from the virial theorem for clusters with the universal gas fraction. At a given temperature, the rms scatter of the gas overdensity radius is only ~7% which translates into a 20% scatter of the gas mass fraction, including statistical scatter due to measurement uncertainties.Comment: ApJ in press, submitted 11/30/9

Analogies between the crossing number and the tangle crossing number

Tanglegrams are special graphs that consist of a pair of rooted binary trees with the same number of leaves, and a perfect matching between the two leaf-sets. These objects are of use in phylogenetics and are represented with straightline drawings where the leaves of the two plane binary trees are on two parallel lines and only the matching edges can cross. The tangle crossing number of a tanglegram is the minimum crossing number over all such drawings and is related to biologically relevant quantities, such as the number of times a parasite switched hosts. Our main results for tanglegrams which parallel known theorems for crossing numbers are as follows. The removal of a single matching edge in a tanglegram with $n$ leaves decreases the tangle crossing number by at most $n-3$, and this is sharp. Additionally, if $\gamma(n)$ is the maximum tangle crossing number of a tanglegram with $n$ leaves, we prove $\frac{1}{2}\binom{n}{2}(1-o(1))\le\gamma(n)<\frac{1}{2}\binom{n}{2}$. Further, we provide an algorithm for computing non-trivial lower bounds on the tangle crossing number in $O(n^4)$ time. This lower bound may be tight, even for tanglegrams with tangle crossing number $\Theta(n^2)$.Comment: 13 pages, 6 figure