Characterizing most irregular small-scale structures in turbulence using local Hölder exponents.

Two scalar fields characterizing respectively pseudo-Hölder exponents and local energy transfers are used to capture the topology and the dynamics of the velocity fields in areas of lesser regularity. The present analysis is conducted using velocity fields from two direct numerical simulations of the Navier-Stokes equations in a triply periodic domain. A typical irregular structure is obtained by averaging over the 213 most irregular events. Such structure is similar to a Burgers vortex, with nonaxisymmetric corrections. A possible explanation for such asymmetry is provided by a detailed time-resolved analysis of birth and death of the irregular structures, which shows that they are connected to vortex interactions, possibly vortex reconnection.

Local estimates of Hölder exponents in turbulent vector fields.

It is still not known whether solutions to the Navier-Stokes equation can develop singularities from regular initial conditions. In particular, a classical and unsolved problem is to prove that the velocity field is Hölder continuous with some exponent h<1 (i.e., not necessarily differentiable) at small scales. Different methods have already been proposed to explore the regularity properties of the velocity field and the estimate of its Hölder exponent h. A first method is to detect potential singularities via extrema of an "inertial" dissipation D*=lim_{ℓ→0}D_{ℓ}^{I} that is independent of viscosity [Duchon and Robert, Nonlinearity 13, 249 (2000)0951-771510.1088/0951-7715/13/1/312]. Another possibility is to use the concept of multifractal analysis that provides fractal dimensions of the subspace of exponents h. However, the multifractal analysis is a global statistical method that only provides global information about local Hölder exponents, via their probability of occurrence. In order to explore the local regularity properties of a velocity field, we have developed a local statistical analysis that estimates locally the Hölder continuity. We have compared outcomes of our analysis with results using the inertial energy dissipation D_{ℓ}^{I}. We observe that the dissipation term indeed gets bigger for velocity fields that are less regular according to our estimates. The exact spatial distribution of the local Hölder exponents however shows nontrivial behavior and does not exactly match the distribution of the inertial dissipation.

Attached flow structure and streamwise energy spectra in a turbulent boundary layer.

On the basis of (i) particle image velocimetry data of a turbulent boundary layer with large field of view and good spatial resolution and (ii) a mathematical relation between the energy spectrum and specifically modeled flow structures, we show that the scalings of the streamwise energy spectrum E_{11}(k_{x}) in a wave-number range directly affected by the wall are determined by wall-attached eddies but are not given by the Townsend-Perry attached eddy model's prediction of these spectra, at least at the Reynolds numbers Re_{τ} considered here which are between 10^{3} and 10^{4}. Instead, we find E_{11}(k_{x})∼k_{x}^{-1-p} where p varies smoothly with distance to the wall from negative values in the buffer layer to positive values in the inertial layer. The exponent p characterizes the turbulence levels inside wall-attached streaky structures conditional on the length of these structures. A particular consequence is that the skin friction velocity is not sufficient to scale E_{11}(k_{x}) for wave numbers directly affected by the wall.

CXCR1 Regulates Pulmonary Anti-Pseudomonas Host Defense.

Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-P. aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway P. aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against P. aeruginosa. Mechanistically, CXCR1 regulates anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with Toll-like receptor 5 expression. These studies define CXCR1 as a novel, noncanonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases.

The Emotional and Psychological Impact on Radiation Therapists of Treating Children.

PURPOSE: The aim of this study was to determine the psychological effects and difficulties that radiation therapists (RTs) experience while treating paediatric patients. This study is intended to provide some information to assist RTs in their occupation and to complement the literature on this topic. METHODS: A survey was conducted to capture data on the emotional effects and opinions of RTs at The Ottawa Hospital Regional Cancer Centre (TOHRCC) treating children with cancer. A questionnaire was created specifically for this study standardized to TOHRCC conditions and methods and inspired from the limited literature around this issue. The study converged on the reactions of RTs while children received radiation treatment at TOHRCC and the impact on their emotional state around this component of their practice. The questionnaire was distributed electronically via e-mail to all RTs within the Radiation Therapy Department at TOHRCC. RESULTS: This study involved 62 of 104 RTs employed at TOHRCC who completed the survey of 20 questions and submitted their responses. Due to the sample size, statistical correlations and links between variables were limited. The questionnaire was analysed based on the answers given by the RTs on the provided Likert scale for each question. The questionnaire showed that gender and age played no major role in the RTs' ability to cope mentally. Half of the RTs had children themselves; and of these, 66% indicated that having children made it somehow more difficult to cope emotionally with paediatric patients. Seventy-five percent of all RTs indicated that the emotional state of parents or care givers of the affected children played a key role in the anxiety they felt during a child's treatment. Eighty-one percent of RTs stated that treating children caused higher anxiety levels than treating adults. Finally, our survey suggests that time constraints play a large part in the RTs' stress level during treatments. CONCLUSION: Overall, treating children did not cause much more distress than treating adults. Results from this survey were used to create a new tool describing the cognitive stages in children to help RTs treat paediatric patients in the future.

Influence of the Si cap layer on the SiGe islands morphology.

Transmission electron microscopy (TEM), atomic force microscopy (AFM), and EDX methods were used to study morphology and chemical composition of SiGe/Si(001) islands grown at 700 degrees C and covered at 550 degrees C and 700 degrees C by Si layers of different thickness. The samples were grown in ultra high vacuum chemical vapor deposition process (UHVCVD) controlled with in situ reflection of high-energy electron diffraction (RHEED). The islands transformed from initial pyramid and dome shapes to lens shape for 1.4 nm and 3.7 nm cap layer thickness at 550 degrees C and 700 degrees C, respectively. An increase of lateral to vertical ratio was observed during the transformation. For the higher depositing temperature the ratio was bigger and was increasing continuously with cap layer thickness. Also, with increasing Si cap layer thickness, the Ge concentration was decreasing, which was more observable for higher capping temperature.

Subcritical dynamo bifurcation in the Taylor-Green flow.

We report direct numerical simulations of dynamo generation for flow generated using a Taylor-Green forcing. We find that the bifurcation is subcritical and show its bifurcation diagram. We connect the associated hysteretic behavior with hydrodynamics changes induced by the action of the Lorentz force. We show the geometry of the dynamo magnetic field and discuss how the dynamo transition can be induced when an external field is applied to the flow.

Influence of turbulence on the dynamo threshold.

We use direct and stochastic numerical simulations of the magnetohydrodynamic equations to explore the influence of turbulence on the dynamo threshold. In the spirit of the Kraichnan-Kazantsev model, we model the turbulence by a noise, with given amplitude, injection scale, and correlation time. The addition of a stochastic noise to the mean velocity significantly alters the dynamo threshold and increases it for any noise at large scale. For small-scale noise, the result depends on its correlation time and on the magnetic Prandtl number.

Study of the localization of iron, ferritin, and hemosiderin in Alzheimer's disease hippocampus by analytical microscopy at the subcellular level.

Previous studies of the structure of core nanocrystals of ferritin (Ft) in the brains of patients with Alzheimer's disease (AD) have shown differences in the mineral compound in comparison with physiological Ft. Both Ft cores have a polyphasic composition but whereas the major phase in physiological Ft is hexagonal ferric iron oxide (ferrihydrite), the major phases in brain AD Ft are two cubic mixed ferric-ferrous iron oxides (magnetite and wüstite). One of these (wüstite) is similar to what is detected in hemosiderin (Hm) cores in primary hemochromatosis (Quintana, C., Cowley, J.M, Marhic, C., 2004. Electron nanodiffraction and high resolution electron microscopy studies of the structure and composition of physiological and pathological ferritin. J. Struct. Biol. 147, 166-178). We have studied, herein, the distribution of iron, Ft, and Hm in sections of AD hippocampus using analytical microscopy. Iron present in Ft cores was directly mapped in a nanoSIMS microscope and the iron distribution has been correlated with the constituent elements N, P, and S. Ft and Hm cores were visualized at an ultrastructural level in an analytical transmission electron microscope. In senile plaques, Ft was observed in the coronal region associated with a non-beta-amyloid component and in the periphery of plaques, together with Hm, in sulfur-rich dense bodies of dystrophic neurites. Hm was also found in lysosomes and siderosomes of glial cells. Ft was observed in the cytoplasm and nucleus of oligodendrocytes. Ft was particularly abundant in myelinated axons in association with oligodendrocyte processes. These findings provide new arguments to support the hypothesis of a dysfunction of Ft (with eventual degradation to Hm) in AD resulting in an increase of toxic brain ferrous ions that may contribute to the production of free radicals that induce both cellular oxidative stress and aged-related myelin breakdown associated with cognitive decline and AD (Bartzokis, G., 2004. Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer's disease. Neurobiol. Aging 25, 5-18).

Nitric oxide voltammetric measurements in the rat brain after gamma irradiation.

The effects of a lethal gamma irradiation were investigated on cerebral NO-ergic system by using a voltammetric method in freely moving rats. It is reported that the cortical NO concentration increases right from the end of the radiation exposure (15 Gy) and reaches a maximal magnitude (+120%) 24 h later. A dose-effect relationship from 2 to 15 Gy for gamma-ray exposure has also been observed. The effects, obtained with either an NO synthase inhibitor nonselective for the different NO synthase isoforms or an NO synthase inhibitor selective for the constitutive isoform, suggest that the radiation-induced increase in NO is likely to be dependent on the inducible NO synthase isoform. Moreover, experiments performed under ex vivo conditions showed that the cortical mRNA level for Ca(++)-independent NO synthase, the brain NOS activity, and urinary nitrites/nitrates increased significantly 24 h after gamma-ray exposure. These results demonstrate that a supralethal whole-body irradiation alters the NO-ergic pathways. The increase in NO obtained under such conditions might constitute a good index of central nervous system radiosensitivity during the acute phase of the radiation syndrome.

Forced stratified turbulence: successive transitions with Reynolds number.

Numerical simulations are made for forced turbulence at a sequence of increasing values of Reynolds number Re keeping fixed a strongly stable, volume-mean density stratification. At smaller values of Re, the turbulent velocity is mainly horizontal, and the momentum balance is approximately cyclostrophic and hydrostatic. This is a regime dominated by so-called pancake vortices, with only a weak excitation of internal gravity waves and large values of the local Richardson number Ri everywhere. At higher values of Re there are successive transitions to (a) overturning motions with local reversals in the density stratification and small or negative values of Ri; (b) growth of a horizontally uniform vertical shear flow component; and (c) growth of a large-scale vertical flow component. Throughout these transitions, pancake vortices continue to dominate the large-scale part of the turbulence, and the gravity wave component remains weak except at small scales.

Nanometric scale investigation of local strain in GaInAs islands by high resolution and analytical TEM.

The continuous displacement field within elastically relaxed GaInAs islands was calculated from digitized HREM images of [110] cross sections of In0.35Ga0.65As layers grown on GaAs by molecular beam epitaxy. Experimental maps of the deformations parallel to the interface (epsilonx) and along the growth direction (epsilonz) were drawn and compared with the ones calculated via the finite element method. It was found that epsilonx exp was systematically higher than epsilonx calc and the significant maximum observed for epsilonz exp within the island could not be found for epsilonz calc. These discrepancies were attributed to a variation of the chemical composition in the island. The maps showing the indium concentration gradient drawn from HREM and FE calculations were compared to quantitative profiles for indium concentration obtained by nanometric X-ray microanalysis in TEM. The measured gradient within the island backs our assumption.

Frequencies and relative levels of clustered damages in DNA exposed to gamma rays in radioquenching vs. nonradioquenching conditions.

Clustered damage induced by ionizing radiation--two or more oxidized bases, abasic sites, or strand breaks within a few DNA helical turns--have been postulated to be major lethal and/or mutagenic sites. Although they have recently been shown to be induced in genomic DNAs by ionizing photons and particles, little is known of the factors that affect their yields or the relative levels of the classes of clusters. Toward this aim we have investigated the effect of DNA milieu, specifically, a nonradioquenching (phosphate) or radioquenching (Tris) solution, upon the generation of clustered lesions in a well-defined molecule, T7 bacteriophage DNA. Irradiation of DNA in Tris reduces the yields of all clustered damages to 1-3% of the levels formed in phosphate. Further, although the percentage of the total clusters in oxidized purine clusters is largely unchanged, and the level of abasic clusters decreases, the frequencies of double-strand breaks and oxidized pyrimidine clusters increase in the radioquenching solution. The ratio of the level of oxidized pyrimidine clusters to double-strand breaks in a DNA in radioquenching solution is similar to that obtained in DNA in human cells, also a radioquenching environment.

Characterization of thermal stability of the Escherichia coli Fapy-DNA glycosylase.

Thermal stability of Escherichia coli Fpg protein was studied using far-UV circular dichroism and intrinsic fluorescence. Experimental data indicate that Fpg irreversibly aggregates under heating above 35 degrees C. Heat aggregation is preceded by tertiary conformational changes of Fpg. However, the secondary structure of the fraction that does not aggregate remains unchanged up to approximately 60 degrees C. The kinetics of heat aggregation occurs with an activation enthalpy of approximately 21 kcal/mol. The fraction of monomers forming aggregates decreases with increasing urea concentration, with essentially no aggregation observed above approximately 3 M urea, suggesting that heat aggregation results from hydrophobic association of partially unfolded proteins. With increasing urea concentration, Fpg unfolds in a two-state reversible transition, with a stability of approximately 3.6 kcal/mol at 25 degrees C. An excellent correlation is observed between the unfolded fraction and loss of activity of Fpg. A simple kinetic scheme that describes both the rates and the extent of aggregation at each temperature is presented.

Effect of single mutations on the specificity of Escherichia coli FPG protein for excision of purine lesions from DNA damaged by free radicals.

The formamidopyrimidine N-DNA glycosylase (Fpg protein) of Escherichia coli is a DNA repair enzyme that is specific for the removal of purine-derived lesions from DNA damaged by free radicals and other oxidative processes. We investigated the effect of single mutations on the specificity of this enzyme for three purine-derived lesions in DNA damaged by free radicals. These damaging agents generate a multiplicity of base products in DNA, with the yields depending on the damaging agent. Wild type Fpg protein (wt-Fpg) removes 8-hydroxyguanine (8-OH-Gua), 4,6-diamino-5-formamidopyrimidine (FapyAde), and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) from damaged DNA with similar specificities. We generated five mutant forms of this enzyme with mutations involving Lys-57-->Gly (FpgK57G), Lys-57-->Arg (FpgK57R), Lys-155-->Ala (FpgK155A), Pro-2-->Gly (FpgP2G), and Pro-2-->Glu (FpgP2E), and purified them to homogeneity. FpgK57G and FpgK57R were functional for removal of FapyAde and FapyGua with a reduced activity when compared with wt-Fpg. The removal of 8-OH-Gua was different in that the specificity of FpgK57G was significantly lower for its removal from irradiated DNA, whereas wt-Fpg, FpgK57G, and FpgK57R excised 8-OH-Gua from H2O2/Fe(III)-EDTA/ascorbic acid-treated DNA with almost the same specificity. FpgK155A and FpgP2G had very low activity and FpgP2E exhibited no activity at all. Michaelis-Menten kinetics of excision was measured and kinetic constants were obtained. The results indicate an important role of Lys-57 residue in the activity of Fpg protein for 8-OH-Gua, but a lesser significant role for formamidopyrimidines. Mutations involving Lys-155 and Pro-2 had a dramatic effect with Pro-2-->Glu leading to complete loss of activity, indicating a significant role of these residues. The results show that point mutations significantly change the specificity of Fpg protein and suggest that point mutations are also expected to change specificities of other DNA repair enzymes.

The HAP1 protein stimulates the turnover of human mismatch-specific thymine-DNA-glycosylase to process 3,N(4)-ethenocytosine residues.

When present in DNA, 3,N(4)-ethenocytosine (epsilon C) residues are potentially mutagenic and carcinogenic in vivo. The enzymatic activity responsible for the repair of the epsilon C residues in human cells is the hTDG protein, the human thymine-DNA-glycosylase that removes thymine in a T/G base pair [Proc. Natl. Acad. Sci., U.S.A., 95 (1998) 8508]. One of the distinctive properties of the hTDG protein is that it remains tightly bound to the AP-site resulting from its glycosylase activity. In this paper we report that the human AP endonuclease, the HAP1 (Ape1, APEX Ref-1) protein, stimulates the processing of epsilon C residues by the hTDG protein in vitro, in a dose-dependent manner. This property of HAP1 protein is specific since E.coli Fpg, Nfo and Nth proteins, all endowed with an AP nicking activity, do not show similar features. The results suggest that the HAP1 protein displaces the hTDG protein bound to the AP-site and therefore increases the turnover of the hTDG protein. However, using a variety of techniques including gel retardation assay, surface plasmon resonance and two-hybrid system, it was not possible to detect evidence for a complex including the substrate, the hTDG and HAP1 proteins.

Scaling laws and vortex profiles in two-dimensional decaying turbulence.

We use high resolution numerical simulations over several hundred of turnover times to study the influence of small scale dissipation onto vortex statistics in 2D decaying turbulence. A scaling regime is detected when the scaling laws are expressed in units of mean vorticity and integral scale, like predicted in Carnevale et al., Phys. Rev. Lett. 66, 2735 (1991), and it is observed that viscous effects spoil this scaling regime. The exponent controlling the decay of the number of vortices shows some trends toward xi=1, in agreement with a recent theory based on the Kirchhoff model [C. Sire and P. H. Chavanis, Phys. Rev. E 61, 6644 (2000)]. In terms of scaled variables, the vortices have a similar profile with a functional form related to the Fermi-Dirac distribution.

Genotoxicity testing of extracts from aflatoxin-contaminated peanut meal, following chemical decontamination.

One of the most important concerns in the decontamination of aflatoxin-containing feed commodities is the safety of the products for food-producing animals and for human consumption of products derived from these animals. A new method, based on the use of florisil and C18 solid phase extraction columns, was developed for the preparation of extracts from decontaminated peanut meal, which allowed testing with in vitro genotoxicity assays without interference of the residual aflatoxin B1. Recovery of degradation products in the extracts was evaluated by the use of radiolabelled [14C]-aflatoxin B1 (AFB1) added to naturally-contaminated peanut meal (3.5 mg AFB1/kg). The meal was treated by a small-scale version of an industrial decontamination process based on ammoniation. Following decontamination, more than 90% of the label could not be extracted from the meal. AFB1 accounted for about 10% of the radiolabel present in the extractable fraction, indicating a total AFB1 reduction of more than 99%. Decontamination of the meal by a number of other small- and industrial-scale ammonia-based processes resulted in similar efficiencies. Application of the extraction procedure resulted in AFB1-rich and AFB1-poor fractions, the latter containing half of the extractable decontamination products but less than 1% of the residual AFB1. Testing in the Salmonella/microsome mutagenicity assay (TA 100, with S9-mix) of the original crude extracts and AFB1-rich fractions prepared from non-treated and decontaminated meal, showed the positive results expected from the AFB1 contents as determined by HPLC analysis. Analysis and testing of the AFB1-poor fractions showed that the various decontamination processes not only resulted in a successful degradation of AFB1 but also did not produce other potent mutagenic compounds. Slight positive results obtained with these extracts were similar for the untreated and treated meals and may be due to unknown compounds originally present in the meal. Results obtained with an unscheduled DNA synthesis (UDS) and Comet assay with rat hepatocytes supported this conclusion. Positive results obtained with the micronucleus assay, using immortalized mouse hepatocytes (GKB), did not clearly reflect the mycotoxin levels and require further examination. It is concluded that the newly developed extraction procedure yields highly reproducible fractions and hence is very suitable for examining the possible formation of less potent degradation products of aflatoxins in short-term genotoxicity tests.

Recognition and kinetics for excision of a base lesion within clustered DNA damage by the Escherichia coli proteins Fpg and Nth.

Ionizing radiation and radiomimetic anticancer agents induce clustered DNA damages that are thought to lead to deleterious biological consequences, due to the challenge that clustered damage may present to the repair machinery of the cell. Specific oligonucleotides, containing either dihydrothymine (DHT) or 7,8-dihydro-8-oxoguanine (8-oxoG) opposite to specific lesions at defined positions on the complementary strand, have been used to determine the kinetic constants, K(M), k(cat), and specificity constants, for excision of DHT and 8-oxoG by the Escherichia coli base excision repair proteins, endonuclease III (Nth) and formamidopyrimidine glycosylase (Fpg), respectively. For excision of DHT opposite to 8-oxoadenine by Nth or Fpg proteins, or 8-oxoG opposite to 8-oxoG by Fpg, the major change in the specificity constant occurs when the second lesion on the complementary strand is one base to the site opposite to DHT or 8-oxoG. The specificity constants for excision of DHT or 8-oxoG by both proteins are reduced by up to 2 orders of magnitude when an abasic site or a strand break is opposite on the complementary strand. Whereas the values of K(M) are only slightly affected by the presence of a second lesion, the major change is seen as a reduction in the values of k(cat). The binding of Fpg protein to oligonucleotides containing 8-oxoG is inhibited, particularly when a single strand break is near to 8-oxoG on the complementary strand. It is inferred that not only the binding affinity of Fpg protein to the base lesion but also the rate of excision of the damaged base is reduced by the presence of another lesion, particularly a single strand break or an AP site on the complementary strand.