Showing papers by "Paul Sabatier University published in 2001"

The concentration of measure phenomenon

Abstract: Concentration functions and inequalities Isoperimetric and functional examples Concentration and geometry Concentration in product spaces Entropy and concentration Transportation cost inequalities Sharp bounds of Gaussian and empirical processes Selected applications References Index

Oxidation state and coordination of Fe in minerals: An Fe K-XANES spectroscopic study

Abstract: High-resolution Fe K-edge XANES spectra of a series of crystalline Fe 2+ - and Fe 3+ -bearing model compounds were measured in an effort to correlate characteristics of the pre-edge feature with oxidation state and local coordination environment of Fe atoms. The model compounds comprise 30 natural minerals and synthetic compounds, with Fe coordination environments ranging from 4 to 12 O atoms for Fe 2+ , including 5-coordinated trigonal bipyramidal Fe 2+ , and from 4 to 6 O atoms for Fe 3+ . Most pre-edge spectra show two components (due to crystal-field splitting) that are located just above the Fermi level. The most useful characteristics of the Fe-K pre-edge for determining Fe oxidation state and coordination number are the position of its centroid and its integrated intensity. The separation between the average pre-edge centroid positions for Fe 2+ and Fe 3+ is 1.4 ± 0.1 eV. Thus, the position of the pre-edge feature can be used as a measure of the average Fe-redox state, with the average pre-edge position for mixed Fe 2+ -Fe 3+ compounds occurring between positions for Fe 2+ and Fe 3+ . The lowest pre-edge normalized heights and integrated intensities are observed for the most centrosymmetric sites of Fe, in agreement with previous studies (see Waychunas et al. 1983). Examination of the pre-edge features of mechanical mixtures of phases containing different proportions of Fe 2+ and Fe 3+ suggests that the pre-edge position and intensity for these mixtures can vary quite non-linearly with the average redox state of Fe. However, distinctly different trends of pre-edge position vs. pre-edge intensity can be observed, depending on the coordination environment of Fe 2+ and Fe 3+ , with an accuracy in redox determination of ±10 mol% provided that the site geometry for each redox state is known. These methods have been used to estimate the Fe 3+ /Fe 2+ ratio in 12 minerals (magnetite, vesuvianite, franklinite, rhodonite, etc.) containing variable/unknown amounts of Fe 2+ /Fe 3+ .

Conformational change of proteins arising from normal mode calculations

Abstract: A normal mode analysis of 20 proteins in 'open' or 'closed' forms was performed using simple potential and protein models. The quality of the results was found to depend upon the form of the protein studied, normal modes obtained with the open form of a given protein comparing better with the conformational change than those obtained with the closed form. Moreover, when the motion of the protein is a highly collective one, then, in all cases considered, there is a single low-frequency normal mode whose direction compares well with the conformational change. When it is not, in most cases there is still a single low-frequency normal mode giving a good description of the pattern of the atomic displacements, as they are observed experimentally during the conformational change. Hence a lot of information on the nature of the conformational change of a protein is often found in a single low-frequency normal mode of its open form. Since this information can be obtained through the normal mode analysis of a model as simple as that used in the present study, it is likely that the property captured by such an analysis is for the most part a property of the shape of the protein itself. One of the points that has to be clarified now is whether or not amino acid sequences have been selected in order to allow proteins to follow a single normal mode direction, as least at the very beginning of their conformational change.

The Luminosity Function of Galaxies in SDSS Commissioning Data

Abstract: In the course of its commissioning observations, the Sloan Digital Sky Survey (SDSS) has produced one of the largest redshift samples of galaxies selected from CCD images. Using 11,275 galaxies complete to r* \ 17.6 over 140 deg2, we compute the luminosity function of galaxies in the r* band over a range (for h \ 1). The result is well-described by a Schechter function with parameters [23 \ M rp \ [16 h3 Mpc~3,

7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes

Abstract: The transcription of eukaryotic protein-coding genes involves complex regulation of RNA polymerase (Pol) II activity in response to physiological conditions and developmental cues. One element of this regulation involves phosphorylation of the carboxy-terminal domain (CTD) of the largest polymerase subunit by a transcription elongation factor, P-TEFb, which comprises the kinase CDK9 and cyclin T1 or T2 (ref. 1). Here we report that in human HeLa cells more than half of the P-TEFb is sequestered in larger complexes that also contain 7SK RNA, an abundant, small nuclear RNA (snRNA) of hitherto unknown function2,3. P-TEFb and 7SK associate in a specific and reversible manner. In contrast to the smaller P-TEFb complexes, which have a high kinase activity, the larger 7SK/P-TEFb complexes show very weak kinase activity. Inhibition of cellular transcription by chemical agents or ultraviolet irradiation trigger the complete disruption of the P-TEFb/7SK complex, and enhance CDK9 activity. The transcription-dependent interaction of P-TEFb with 7SK may therefore contribute to an important feedback loop modulating the activity of RNA Pol II.

An rpsL Cassette, Janus, for Gene Replacement through Negative Selection in Streptococcus pneumoniae

Abstract: Natural genetic transformation offers a direct route by which synthetic gene constructs can be placed into the single circular chromosome of Streptococcus pneumoniae. However, the lack of a general negative-selection marker has hampered the introduction of constructs that do not confer a selectable phenotype. A 1.3-kb cassette was constructed comprising a kanamycin (Kn) resistance marker (kan) and a counterselectable rpsL(+) marker. The cassette conferred dominant streptomycin (Sm) sensitivity in an Sm-resistant background in S. pneumoniae. It was demonstrated that it could be used in a two-step transformation procedure to place DNA of arbitrary sequence at a chosen target site. The first transformation into an Sm-resistant strain used the cassette to tag a target gene on the chromosome by homologous recombination while conferring Kn resistance but Sm sensitivity on the recombinant. Replacement of the cassette by an arbitrary segment of DNA during a second transformation restored Sm resistance (and Kn sensitivity), allowing construction of silent mutations and deletions or other gene replacements which lack a selectable phenotype. It was also shown that gene conversion occurred between the two rpsL alleles in a process that depended on recA and that was susceptible to correction by mismatch repair.

On the breakdown of boundary layer streaks

Abstract: A scenario of transition to turbulence likely to occur during the development of natural disturbances in a flat-plate boundary layer is studied. The perturbations at the leading edge of the flat plate that show the highest potential for transient energy amplication consist of streamwise aligned vortices. Due to the lift-up mechanism these optimal disturbances lead to elongated streamwise streaks downstream, with signicant spanwise modulation. Direct numerical simulations are used to follow the nonlinear evolution of these streaks and to verify secondary instability calculations. The theory is based on a linear Floquet expansion and focuses on the temporal, inviscid instability of these flow structures. The procedure requires integration in the complex plane, in the coordinate direction normal to the wall, to properly identify neutral modes belonging to the discrete spectrum. The streak critical amplitude, beyond which streamwise travelling waves are excited, is about 26% of the free-stream velocity. The sinuous instability mode (either the fundamental or the subharmonic, depending on the streak amplitude) represents the most dangerous disturbance. Varicose waves are more stable, and are characterized by a critical amplitude of about 37%. Stability calculations of streamwise streaks employing the shape assumption, carried out in a parallel investigation, are compared to the results obtained here using the nonlinearly modied mean elds; the need to consider a base flow which includes mean flow modication and harmonics of the fundamental streak is clearly demonstrated.

Possibility Theory, Probability Theory and Multiple-Valued Logics: A Clarification

Abstract: There has been a long-lasting misunderstanding in the literature of artificial intelligence and uncertainty modeling, regarding the role of fuzzy set theory and many-valued logics. The recurring question is that of the mathematical and pragmatic meaningfulness of a compositional calculus and the validity of the excluded middle law. This confusion pervades the early developments of probabilistic logic, despite early warnings of some philosophers of probability. This paper tries to clarify this situation. It emphasizes three main points. First, it suggests that the root of the controversies lies in the unfortunate confusion between degrees of belief and what logicians call “degrees of truth”. The latter are usually compositional, while the former cannot be so. This claim is first illustrated by laying bare the non-compositional belief representation embedded in the standard propositional calculus. It turns out to be an all-or-nothing version of possibility theory. This framework is then extended to discuss the case of fuzzy logic versus graded possibility theory. Next, it is demonstrated that any belief representation where compositionality is taken for granted is bound to at worst collapse to a Boolean truth assignment and at best to a poorly expressive tool. Lastly, some claims pertaining to an alleged compositionality of possibility theory are refuted, thus clarifying a pervasive confusion between possibility theory axioms and fuzzy set basic connectives.

Mutation spectrum and splicing variants in the OPA1 gene.

Abstract: Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic neuropathy that features low visual acuity leading in many cases to legal blindness. We have recently shown, with others, that mutations in the OPA1 gene encoding a dynamin-related mitochondrial protein, underlie the dominant form of optic atrophy. Here we report that OPA1 has eight mRNA isoforms as a result of the alternative splicing of exon 4 and two novel exons named 4b and 5b. In addition, we screened a cohort of 19 unrelated patients with dominant optic atrophy by direct sequencing of the 30 OPA1 exons (including exons 4b and 5b) and found mutations in 17 (89%) of them of which 8 were novel. A majority of these mutations were truncative (65%) and located in exons 8 to 28, but a number of them were amino acid changes predominantly found in the GTPase domain (exons 8 to 15). We hypothesize that at least two modifications of OPA1 may lead to dominant optic atrophy, that is alteration in GTPase activity and loss of the last seven C-terminal amino acids that putatively interact with other proteins.

RNomics: an experimental approach that identifies 201 candidates for novel, small, non-messenger RNAs in mouse

Abstract: In mouse brain cDNA libraries generated from small RNA molecules we have identified a total of 201 different expressed RNA sequences potentially encoding novel small non-messenger RNA species (snmRNAs). Based on sequence and structural motifs, 113 of these RNAs can be assigned to the C/D box or H/ACA box subclass of small nucleolar RNAs (snoRNAs), known as guide RNAs for rRNA. While 30 RNAs represent mouse homologues of previously identified human C/D or H/ACA snoRNAs, 83 correspond to entirely novel snoRNAs. Among these, for the first time, we identified four C/D box snoRNAs and four H/ACA box snoRNAs predicted to direct modifications within U2, U4 or U6 small nuclear RNAs (snRNAs). Furthermore, 25 snoRNAs from either class lacked antisense elements for rRNAs or snRNAs. Therefore, additional snoRNA targets have to be considered. Surprisingly, six C/D box snoRNAs and one H/ACA box snoRNA were expressed exclusively in brain. Of the 88 RNAs not belonging to either snoRNA subclass, at least 26 are probably derived from truncated heterogeneous nuclear RNAs (hnRNAs) or mRNAs. Short interspersed repetitive elements (SINEs) are located on five RNA sequences and may represent rare examples of transcribed SINEs. The remaining RNA species could not as yet be assigned either to any snmRNA class or to a part of a larger hnRNA/mRNA. It is likely that at least some of the latter will represent novel, unclassified snmRNAs.

Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial

Abstract: Objective To evaluate the ability of diacerein, an interleukin-1β inhibitor, to slow the progressive decrease in joint space width observed in patients with hip osteoarthritis (OA). Methods In this randomized, double-blind, placebo-controlled 3-year study, 507 patients with primary OA of the hip (by the American College of Rheumatology criteria) received diacerein (50 mg twice a day) or placebo. The minimal hip joint space width was measured by a central reader on yearly pelvic radiographs, using a 0.1-mm–graduated magnifying glass. Results Baseline characteristics were comparable in the 2 treatment groups (255 patients receiving diacerein, 252 receiving placebo); 238 patients (47%) discontinued the study, mainly because of adverse events in the diacerein group (25% versus 12% with placebo) and because of inefficacy in the placebo group (14% versus 7% with diacerein). The percentage of patients with radiographic progression, defined by a joint space loss of at least 0.5 mm, was significantly lower in patients receiving diacerein than in patients receiving placebo, both in the intent-to-treat analysis and in the completer analysis (50.7% versus 60.4% [P = 0.036] and 47.3% versus 62.3% [P = 0.007], respectively). In those patients who completed 3 years of treatment, the rate of joint space narrowing was significantly lower with diacerein (mean ± SD 0.18 ± 0.25 mm/year versus 0.23 ± 0.23 mm/year with placebo; P = 0.042). Diacerein had no evident effect on the symptoms of OA in this study. However, a post hoc covariate analysis that took into account the use of analgesics and antiinflammatory drugs showed an effect of diacerein on the Lequesne functional index. Diacerein was well tolerated during the 3-year study. The most frequent adverse events were transient changes in bowel habits. Conclusion This study confirms previous clinical findings indicating that the demonstration of a structure-modifying effect in hip OA is feasible, and shows, for the first time, that treatment with diacerein for 3 years has a significant structure-modifying effect as compared with placebo, coupled with a good safety profile. The clinical relevance of these findings requires further investigation.

Seeking Categories in the Brain

Abstract: Categorizing the objects that we see is a fundamental property of our brain and the brains of other mammals In their enlightening Perspective, Thorpe and Fabre-Thorpe discuss exciting new findings in monkeys ( Freedman et al) that identify neurons in the prefrontal cortex that are primarily responsible for categorizing objects

Eyes first! Eye processing develops before face processing in children.

Abstract: Faces and eyes are critical social stimuli which adults process with ease, but how this expertise develops is not yet understood. Neural changes associated with face and eye processing were investigated developmentally using ERPs (N170), in 128 subjects (4-15 year olds and adults). Stimuli included upright faces to assess configural processing, eyes and inverted faces to assess feature-based processing. N170 was present in the youngest children with similar patterns of face sensitivity seen in adults. Development of N170 to upright faces continued until adulthood, suggesting slow maturation of configural processing. In contrast, N170 was shorter latency and much larger to eyes than faces in children and was mature by 11 years, suggesting the early presence of an eye detector, with a rapid maturational course.

Mechanisms controlling the transition from glow silent discharge to streamer discharge in nitrogen

Abstract: Low-energy dielectric-barrier controlled discharges in nitrogen are studied by undertaking electrical measurements to determine mechanisms controlling the transition from glow to streamer-like discharge. The highest and the lowest values of the frequency and the amplitude of power supply voltage leading to a glow discharge have been found dependent on the gas flow and the nature of the surface in contact with the discharge. These boundary values have been related to the criteria necessary for initiating a Townsend breakdown rather than a streamer breakdown commonly observed under such conditions. This implies: (1) that the seed electron density just before the breakdown is high enough to allow the development of numerous small avalanches under a low field avoiding the formation of only one large avalanche mechanism at the origin of the streamer formation; and (2) to let the time for ions issued from the first avalanches to reach the cathode before the electrical field becomes large enough to induce the formation of large avalanches. Practically, the transition from a Townsend breakdown to a streamer breakdown is analyzed from electrical measurements data coupled to the visual aspect of the discharge. Without any gas flow, the obtaining of an atmospheric pressure glow discharge (APGD) is mainly limited by the species etched from the surface in contact with the gas. Indeed, these species can be quenchers of the nitrogen metastable molecules, which are the species at the origin of the formation of seed electrons via the Penning effect. This limitation can be overcome by the use of a laminar gas flow. However, this type of gas flow through the discharge induces a depletion of N/sub 2/ metastables and, consequently, influences the electron density at the entrance of the discharge, leading to a tendency on this part of the discharge to transit to a streamer-like one.

Galosian Obstructions to Integrability of Hamiltonian Systems II

Abstract: An inconvenience of all the known galoisian formulations of Ziglin's non-integrability theory is the Fhchsian condition at the singular points of the variational equations. We avoid this restriction. Moreover we prove that a necessary condition for meromorphic complete integrability (in Liouville sense) is that the identity component of the Galois group of the variational equation (in the complex domain) must be abelian. We test the efficacy of these new approaches on some examples. We will give some non academic applications in two following papers