Nonlinear Dynamics of Rotating Multi-Component Pair Plasmas and e-p-i Plasmas

The propagation of small amplitude stationary profile nonlinear electrostatic excitations in a pair plasma is investigated, mainly drawing inspiration from experiments on fullerene pair-ion plasmas. Two distinct pair ion species are considered of opposite polarity and same mass, in addition to a massive charged background species, which is assumed to be stationary, given the frequency scale of interest. In the pair-ion context, the third species is thought of as a background defect (e.g. charged dust) component. On the other hand, the model also applies formally to electron-positron-ion (e-p-i) plasmas, if one neglects electron-positron annihilation. A two-fluid plasma model is employed, incorporating both Lorentz and Coriolis forces, thus taking into account the interplay between the gyroscopic (Larmor) frequency ?c and the (intrinsic) plasma rotation frequency O0. By employing a multi-dimensional reductive perturbation technique, a Zakharov-Kuznetsov (ZK) type equation is derived for the evolution of the electric potential perturbation. Assuming an arbitrary direction of propagation, with respect to the magnetic field, we derive the exact form of nonlinear solutions, and study their characteristics. A parametric analysis is carried out, as regards the effect of the dusty plasma composition (background number density), species temperature(s) and the relative strength of rotation to Larmor frequencies. It is shown that the Larmor and mechanical rotation affect the pulse dynamics via a parallel-to-transverse mode coupling diffusion term, which in fact diverges at ?c ? ±2O0. Pulses collapse at this limit, as nonlinearity fails to balance dispersion. The analysis is complemented by investigating critical plasma compositions, in fact near-symmetric (T- ˜ T+) “pure” (n- ˜ n+) pair plasmas, i.e. when the concentration of the 3rd background species is negligible, case in which the (quadratic) nonlinearity vanishes, so one needs to resort to higher order nonlinear theory. A modified ZK equation is derived and analyzed. Our results are of relevance in pair-ion (fullerene) experiments and also potentially in astrophysical environments, e.g. in pulsars.

Framework for Establishing Limits of Tabular Aerodynamic Models for Flight Dynamics Analysis

This paper describes the use of the Euler equations for the generation and testing of tabular aerodynamic models for flight dynamics analysis. Maneuvers for the AGARD Standard Dynamics Model sharp leading-edge wind-tunnel geometry are considered as a test case. Wind-tunnel data is first used to validate the prediction of static and dynamic coefficients at both low and high angles, featuring complex vortical flow, with good agreement obtained at low to moderate angles of attack. Then the generation of aerodynamic tables is described based on a data fusion approach. Time-optimal maneuvers are generated based on these tables, including level flight trim, pull-ups at constant and varying incidence, and level and 90 degrees turns. The maneuver definition includes the aircraft states and also the control deflections to achieve the motion. The main point of the paper is then to assess the validity of the aerodynamic tables which were used to define the maneuvers. This is done by replaying them, including the control surface motions, through the time accurate computational fluid dynamics code. The resulting forces and moments are compared with the tabular values to assess the presence of inadequately modeled dynamic or unsteady effects. The agreement between the tables and the replay is demonstrated for slow maneuvers. Increasing rate maneuvers show discrepancies which are ascribed to vortical flow hysteresis at the higher rate motions. The framework is suitable for application to more complex viscous flow models, and is powerful for the assessment of the validity of aerodynamics models of the type currently used for studies of flight dynamics.

Dynamics of intense laser propagation in underdense plasma: Polarization dependence

We present a comprehensive numerical study of the dynamics of an intense laser pulse as it propagates through an underdense plasma in two and three dimensions. By varying the background plasma density and the polarization of the laser beam, significant differences are found in terms of energy transport and dissipation, in agreement with recently reported experimental results. Below the threshold for relativistic self-focusing, the plasma and laser dynamics are observed to be substantially insensitive to the initial laser polarization, since laser transport is dominated by ponderomotive effects. Above this threshold, relativistic effects become important, and laser energy is dissipated either by plasma heating (p-polarization) or by trapping of electromagnetic energy into plasma cavities (s-polarization) or by a combination of both (circular polarization). Besides the fundamental interest of this study, the results presented are relevant to applications such as plasma-based accelerators, x-ray lasers, and fast-ignition inertial confinement fusion. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4737151]

Nonlinear dynamics of multidimensional electrostatic excitations in nonthermal plasmas

Electrostatic solitary waves in plasmas are the focus of many current studies of localized electrostatic disturbances in both laboratory and astrophysical plasmas. Motivated by recent experimental observations, in which electrostatic solitary structures were detected in laser-plasma experiments, we have undertaken an investigation of the nonlinear dynamics of plasma evolving in two dimensions, in the presence of excess superthermal background electrons. We investigate the effect of a magnetic field on weakly nonlinear ion-acoustic waves. Deviation from the Maxwellian distribution is effectively modelled by the kappa model. A linear dispersion relation is derived, and a decrease in frequency and phase speed in both parallel and perpendicular modes can be seen, which is due to excess superthermal electrons, and which is stronger in the upper mode, and hardly noticeable in the lower (acoustic) mode. We show that ion-acoustic solitary waves can be generated during the nonlinear evolution of a plasma fluid, and their nonlinear propagation is governed by a Zakharov-Kuznetsov (ZK) type equation. A multiple scales perturbation technique is used to derive the ZK equation. Shock excitations can be produced if we allow for dissipation in the model, resulting in a Zakharov-Kuznetsov Burgers type equation. Different types of shock solutions and solitary waves are obtained, depending on the relation between the system parameters, and the effect of these on electrostatic shock structures is investigated numerically. A parametric investigation is conducted into the role of plasma nonthermality and magnetic field strength. © 2013 IOP Publishing Ltd.

Adaptive Fusion Of Particle Filtering And Spatio-Temporal Motion Energy For Human Tracking

Object tracking is an active research area nowadays due to its importance in human computer interface, teleconferencing and video surveillance. However, reliable tracking of objects in the presence of occlusions, pose and illumination changes is still a challenging topic. In this paper, we introduce a novel tracking approach that fuses two cues namely colour and spatio-temporal motion energy within a particle filter based framework. We conduct a measure of coherent motion over two image frames, which reveals the spatio-temporal dynamics of the target. At the same time, the importance of both colour and motion energy cues is determined in the stage of reliability evaluation. This determination helps maintain the performance of the tracking system against abrupt appearance changes. Experimental results demonstrate that the proposed method outperforms the other state of the art techniques in the used test datasets.

IHG-1 increases mitochondrial fusion and bioenergetic function

Induced in high glucose-1 (IHG-1) is a conserved mitochondrial protein associated with diabetic nephropathy (DN) that amplifies profibrotic transforming growth factor (TGF)-β1 signaling and increases mitochondrial biogenesis. Here we report that inhibition of endogenous IHG-1 expression results in reduced mitochondrial respiratory capacity, ATP production, and mitochondrial fusion. Conversely, overexpression of IHG-1 leads to increased mitochondrial fusion and also protects cells from reactive oxygen species-induced apoptosis. IHG-1 forms complexes with known mediators of mitochondrial fusion-mitofusins (Mfns) 1 and 2-and enhances the GTP-binding capacity of Mfn2, suggesting that IHG-1 acts as a guanine nucleotide exchange factor. IHG-1 must be localized to mitochondria to interact with Mfn1 and Mfn2, and this interaction is necessary for increased IHG-1-mediated mitochondrial fusion. Together, these findings indicate that IHG-1 is a novel regulator of both mitochondrial dynamics and bioenergetic function and contributes to cell survival following oxidant stress. We propose that in diabetic kidney disease increased IHG-1 expression protects cell viability and enhances the actions of TGF-β, leading to renal proximal tubule dedifferentiation, an important event in the pathogenesis of this devastating condition.

Novel role of androgens in mitochondrial fission and apoptosis

Androgen and androgen receptors (AR) play critical roles in the proliferation of prostate cancer through transcriptional regulation of target genes. Here, we found that androgens upregulated the expression of dynamin-related protein 1 (Drp1), which is involved in the induction of mitochondrial fission, a common event in mitosis and apoptosis. Clinical tissue samples and various prostate cancer cell lines revealed a positive correlation between Drp1 and AR levels. Treatment of androgen-sensitive cells with an AR agonist, R1881, and antagonist, bicalutamide, showed that Drp1 is transcriptionally regulated by androgens, as confirmed by an AR ChIP-seq assay. Live imaging experiments using pAcGFP1-Mito stably transfected LNCaP (mito-green) cells revealed that androgen did not induce significant mitochondrial fission by itself, although Drp1 was upregulated. However, when treated with CGP37157 (CGP), an inhibitor of mitochondrial Ca²⁺ efflux, these cells exhibited mitochondrial fission, which was further enhanced by pretreatment with R1881, suggesting that androgen-induced Drp1 expression facilitated CGP-induced mitochondrial fission. This enhanced mitochondrial fission was correlated with increased apoptosis. Transfection with dominant-negative (DN-Drp1, K38A) rescued cells from increased apoptosis, confirming the role of androgen-induced Drp1 in the observed apoptosis with combination treatment. Furthermore, we found that CGP reduced the expression of Mfn1, a protein that promotes mitochondrial fusion, a process which opposes fission. We suggest that androgen-increased Drp1 enhanced mitochondrial fission leading to apoptosis. The present study shows a novel role for androgens in the regulation of mitochondrial morphology that could potentially be utilized in prostate cancer therapy.

Recherche des facteurs génétiques à l’origine de la maladie de Parkinson dans la population canadienne-française du Québec

La maladie de Parkinson (MP) est une affection neurodégénérative invalidante et incurable. Il est maintenant clairement établi que d’importants déterminants génétiques prédisposent à son apparition. La recherche génétique sur des formes familiales de la MP a mené à la découverte d’un minimum de six gènes causatifs (SNCA, LRRK2, Parkin, PINK1, DJ-1 and GBA) et certains, par exemple LRRK2, contiennent des variations génétiques qui prédisposent également aux formes sporadiques. La caractérisation des protéines codées par ces gènes a mené à une meilleure compréhension des mécanismes moléculaires sousjacents. Toutefois, en dépit de ces efforts, les causes menant à l’apparition de la MP restent inconnues pour la majorité des patients. L’objectif général des présents travaux était d’identifier des mutations prédisposant à la MP dans la population canadienne-française du Québec à partir d’une cohorte composée principalement de patients sporadiques. Le premier volet de ce projet consistait à déterminer la présence de mutations de LRRK2 dans notre cohorte en séquençant directement les exons contenant la majorité des mutations pathogéniques et en effectuant une étude d’association. Nous n’avons identifié aucune mutation et l’étude d’association s’est avérée négative, suggérant ainsi que LRRK2 n’est pas une cause significative de la MP dans la population canadienne-française. La deuxième partie du projet avait pour objectif d’identifier de nouveaux gènes causatifs en séquençant directement des gènes candidats choisis à cause de leurs implications dans différents mécanismes moléculaires sous-tendant la MP. Notre hypothèse de recherche était basée sur l’idée que la MP est principalement due à des mutations individuellement rares dans un grand nombre de gènes différents. Nous avons identifié des mutations rares dans les gènes PICK1 et MFN1. Le premier code pour une protéine impliquée dans la régulation de la transmission du glutamate tandis que le second est un des acteurs-clés du processus de fusion mitochondriale. Nos résultats, qui devront être répliqués, suggèrent que le séquençage à grande échelle pourrait être une méthode prometteuse d’élucidation des facteurs de prédisposition génétiques à la MP ; ils soulignent l’intérêt d’utiliser une population fondatrice comme les canadiens-français pour ce type d’étude et devraient permettre d’approfondir les connaissances sur la pathogénèse moléculaire de la MP.

Scanning tunneling microscopy and molecular dynamics study of the Li2TiO3(001) surface

We have investigated the (001) surface structure of lithium titanate (Li2TiO3) using auger electron spectroscopy (AES), low-energy electron diffraction (LEED), and scanning tunneling microscopy (STM). Li2TiO3 is a potential fusion reactor blanket material. After annealing at 1200 K, LEED demonstrated that the Li2TiO3(001) surface was well ordered and not reconstructed. STM imaging showed that terraces are separated in height by about 0.3 nm suggesting a single termination layer. Moreover, hexagonal patterns with a periodicity of ∼0.4 nm are observed. On the basis of molecular dynamics (MD) simulations, these are interpreted as a dynamic arrangement of Li atoms.

Projectile breakup dynamics for (6)Li+(59)Co: Kinematical analysis of alpha-d coincidences

A study of the kinematics of the alpha-d coincidences in the (6)Li + (59)Co system at a bombarding energy of E(lab) = 29.6MeV is presented. With exclusive measurements performed over different angular intervals it is possible to identify the respective contributions of the sequential and direct projectile breakup components. The angular distributions of both breakup components are fairly well described by the Continuum-Discretized Coupled-Channels framework (CDCC). Furthermore, a careful analysis of these processes using a semiclassical approach provides information on both their lifetime and their distance of occurrence with respect to the target. Breakup to the low-lying (near-threshold) continuum is delayed, and happens at large internuclear distances. This suggests that the influence of the projectile breakup on the complete fusion process can be related essentially to the direct breakup to the (6)Li high-lying continuum spectrum.

Molecular Dynamics simulations of track formation at different ensembles

A series of Molecular Dynamics simulations of thermal spikes has been run in zircon. For two different ensembles: microcanonical one and a combination of microcanonical one acting on the simulation core with Langevin one on the side walls of simulation. Depending on the used ensemble, different track-formation threshold energies were found. When the combined ensemble is carried out, the total energy of the simulations varies with the temperature which can influence how annealing fission-track models should deal with the lattice recovery. A fission-track annealing model is tested with the simulation results. © 2012 Elsevier Ltd. All rights reserved.

Assembling a xylanase-lichenase chimera through all-atom molecular dynamics simulations

Multifunctional enzyme engineering can improve enzyme cocktails for emerging biofuel technology. Molecular dynamics through structure-based models (SB) is an effective tool for assessing the tridimensional arrangement of chimeric enzymes as well as for inferring the functional practicability before experimental validation. This study describes the computational design of a bifunctional xylanase-lichenase chimera (XylLich) using the xynA and bglS genes from Bacillus subtilis. In silico analysis of the average solvent accessible surface area (SAS) and the root mean square fluctuation (RMSF) predicted a fully functional chimera, with minor fluctuations and variations along the polypeptide chains. Afterwards, the chimeric enzyme was built by fusing the xynA and bglS genes. XylLich was evaluated through small-angle X-ray scattering (SAXS) experiments, resulting in scattering curves with a very accurate fit to the theoretical protein model. The chimera preserved the biochemical characteristics of the parental enzymes, with the exception of a slight variation in the temperature of operation and the catalytic efficiency (k cat/Km). The absence of substantial shifts in the catalytic mode of operation was also verified. Furthermore, the production of chimeric enzymes could be more profitable than producing a single enzyme separately, based on comparing the recombinant protein production yield and the hydrolytic activity achieved for XylLich with that of the parental enzymes. © 2013 Elsevier B.V. All rights reserved.

Alfven eigenmode properties and dynamics in the TJ-II stellarator

Alfven eigenmodes (AEs) were studied in neutral beam injection (NBI) heated plasmas in the TJ-II stellarator using a heavy ion beam probe (HIBP) in the core, and by Langmuir (LP) and Mirnov probes (MP) at the edge. AEs were detected over the whole plasma radius by the HIBP with a spatial resolution of about 1 cm. AE-induced oscillations were detected in the plasma density n(e), electric potential phi and poloidal magnetic field B-pol with frequencies 50 kHz < f(AE) < 300 kHz. The LP, MP and HIBP data showed a high level of coherency for specific branches of AEs. Poloidal mode wave-vectors k(theta), mode numbers m (m < 8) and propagation velocities V-theta similar to 30 km s(-1) were detected for various branches of AEs, having different radial locations. When the density rose due to NBI fuelling, the AE frequency decreased as predicted by the Alfven law f(AE) similar to n(e)(-1/2). During the AE frequency decay the following new AE features were observed: (i) the poloidal wave-vector k(theta) and mode number m remained constant, (ii) the cross-phases between the oscillations in B-pol, n(e) and electric potential remained constant, having an individual value for each AE branch, (iii) V-theta decreased proportional to the AE frequency. The interaction of the AEs with the bulk (thermal) plasma resulted in clearly pronounced quasi-coherent peaks in the electrostatic turbulent particle flux spectra. Various AE branches exhibited different contributions to the particle flux: outward, inward and also zero, depending on the phase relations between the oscillations in E-pol and n(e), which are specific for each branch. A comparison with MHD mode modelling indicated that some of the more prominent frequency branches can be identified as radially extended helical AEs.

Dynamical analysis of turbulence in fusion plasmas and nonlinear waves

Turbulence is one of the key problems of classical physics, and it has been the object of intense research in the last decades in a large spectrum of problems involving fluids, plasmas, and waves. In order to review some advances in theoretical and experimental investigations on turbulence a mini-symposium on this subject was organized in the Dynamics Days South America 2010 Conference. The main goal of this mini-symposium was to present recent developments in both fundamental aspects and dynamical analysis of turbulence in nonlinear waves and fusion plasmas. In this paper we present a summary of the works presented at this mini-symposium. Among the questions to be addressed were the onset and control of turbulence and spatio-temporal chaos. (C) 2011 Elsevier B. V. All rights reserved.

Studies of OPA1 pathogenic mechanisms in Dominant Optic Atrophy and novel protein function in mitochondrial DNA stability

The mitochondrion is an essential cytoplasmic organelle that provides most of the energy necessary for eukaryotic cell physiology. Mitochondrial structure and functions are maintained by proteins of both mitochondrial and nuclear origin. These organelles are organized in an extended network that dynamically fuses and divides. Mitochondrial morphology results from the equilibrium between fusion and fission processes, controlled by a family of “mitochondria-shaping” proteins. It is becoming clear that defects in mitochondrial dynamics can impair mitochondrial respiration, morphology and motility, leading to apoptotic cell death in vitro and more or less severe neurodegenerative disorders in vivo in humans. Mutations in OPA1, a nuclear encoded mitochondrial protein, cause autosomal Dominant Optic Atrophy (DOA), a heterogeneous blinding disease characterized by retinal ganglion cell degeneration leading to optic neuropathy (Delettre et al., 2000; Alexander et al., 2000). OPA1 is a mitochondrial dynamin-related guanosine triphosphatase (GTPase) protein involved in mitochondrial network dynamics, cytochrome c storage and apoptosis. This protein is anchored or associated on the inner mitochondrial membrane facing the intermembrane space. Eight OPA1 isoforms resulting from alternative splicing combinations of exon 4, 4b and 5b have been described (Delettre et al., 2001). These variants greatly vary among diverse organs and the presence of specific isoforms has been associated with various mitochondrial functions. The different spliced exons encode domains included in the amino-terminal region and contribute to determine OPA1 functions (Olichon et al., 2006). It has been shown that exon 4, that is conserved throughout evolution, confers functions to OPA1 involved in maintenance of the mitochondrial membrane potential and in the fusion of the network. Conversely, exon 4b and exon 5b, which are vertebrate specific, are involved in regulation of cytochrome c release from mitochondria, and activation of apoptosis, a process restricted to vertebrates (Olichon et al., 2007). While Mgm1p has been identified thanks to its role in mtDNA maintenance, it is only recently that OPA1 has been linked to mtDNA stability. Missense mutations in OPA1 cause accumulation of multiple deletions in skeletal muscle. The syndrome associated to these mutations (DOA-1 plus) is complex, consisting of a combination of dominant optic atrophy, progressive external ophtalmoplegia, peripheral neuropathy, ataxia and deafness (Amati- Bonneau et al., 2008; Hudson et al., 2008). OPA1 is the fifth gene associated with mtDNA “breakage syndrome” together with ANT1, PolG1-2 and TYMP (Spinazzola et al., 2009). In this thesis we show for the first time that specific OPA1 isoforms associated to exon 4b are important for mtDNA stability, by anchoring the nucleoids to the inner mitochondrial membrane. Our results clearly demonstrate that OPA1 isoforms including exon 4b are intimately associated to the maintenance of the mitochondrial genome, as their silencing leads to mtDNA depletion. The mechanism leading to mtDNA loss is associated with replication inhibition in cells where exon 4b containing isoforms were down-regulated. Furthermore silencing of exon 4b associated isoforms is responsible for alteration in mtDNA-nucleoids distribution in the mitochondrial network. In this study it was evidenced that OPA1 exon 4b isoform is cleaved to provide a 10kd peptide embedded in the inner membrane by a second transmembrane domain, that seems to be crucial for mitochondrial genome maintenance and does correspond to the second transmembrane domain of the yeasts orthologue encoded by MGM1 or Msp1, which is also mandatory for this process (Diot et al., 2009; Herlan et al., 2003). Furthermore in this thesis we show that the NT-OPA1-exon 4b peptide co-immuno-precipitates with mtDNA and specifically interacts with two major components of the mitochondrial nucleoids: the polymerase gamma and Tfam. Thus, from these experiments the conclusion is that NT-OPA1- exon 4b peptide contributes to the nucleoid anchoring in the inner mitochondrial membrane, a process that is required for the initiation of mtDNA replication and for the distribution of nucleoids along the network. These data provide new crucial insights in understanding the mechanism involved in maintenance of mtDNA integrity, because they clearly demonstrate that, besides genes implicated in mtDNA replications (i.e. polymerase gamma, Tfam, twinkle and genes involved in the nucleotide pool metabolism), OPA1 and mitochondrial membrane dynamics play also an important role. Noticeably, the effect on mtDNA is different depending on the specific OPA1 isoforms down-regulated, suggesting the involvement of two different combined mechanisms. Over two hundred OPA1 mutations, spread throughout the coding region of the gene, have been described to date, including substitutions, deletions or insertions. Some mutations are predicted to generate a truncated protein inducing haploinsufficiency, whereas the missense nucleotide substitutions result in aminoacidic changes which affect conserved positions of the OPA1 protein. So far, the functional consequences of OPA1 mutations in cells from DOA patients are poorly understood. Phosphorus MR spectroscopy in patients with the c.2708delTTAG deletion revealed a defect in oxidative phosphorylation in muscles (Lodi et al., 2004). An energetic impairment has been also show in fibroblasts with the severe OPA1 R445H mutation (Amati-Bonneau et al., 2005). It has been previously reported by our group that OPA1 mutations leading to haploinsufficiency are associated in fibroblasts to an oxidative phosphorylation dysfunction, mainly involving the respiratory complex I (Zanna et al., 2008). In this study we have evaluated the energetic efficiency of a panel of skin fibroblasts derived from DOA patients, five fibroblast cell lines with OPA1 mutations causing haploinsufficiency (DOA-H) and two cell lines bearing mis-sense aminoacidic substitutions (DOA-AA), and compared with control fibroblasts. Although both types of DOA fibroblasts maintained a similar ATP content when incubated in a glucose-free medium, i.e. when forced to utilize the oxidative phosphorylation only to produce ATP, the mitochondrial ATP synthesis through complex I, measured in digitonin-permeabilized cells, was significantly reduced in cells with OPA1 haploinsufficiency only, whereas it was similar to controls in cells with the missense substitutions. Furthermore, evaluation of the mitochondrial membrane potential (DYm) in the two fibroblast lines DOA-AA and in two DOA-H fibroblasts, namely those bearing the c.2819-2A>C mutation and the c.2708delTTAG microdeletion, revealed an anomalous depolarizing response to oligomycin in DOA-H cell lines only. This finding clearly supports the hypothesis that these mutations cause a significant alteration in the respiratory chain function, which can be unmasked only when the operation of the ATP synthase is prevented. Noticeably, oligomycin-induced depolarization in these cells was almost completely prevented by preincubation with cyclosporin A, a well known inhibitor of the permeability transition pore (PTP). This results is very important because it suggests for the first time that the voltage threshold for PTP opening is altered in DOA-H fibroblasts. Although this issue has not yet been addressed in the present study, several are the mechanisms that have been proposed to lead to PTP deregulation, including in particular increased reactive oxygen species production and alteration of Ca2+ homeostasis, whose role in DOA fibroblasts PTP opening is currently under investigation. Identification of the mechanisms leading to altered threshold for PTP regulation will help our understanding of the pathophysiology of DOA, but also provide a strategy for therapeutic intervention.