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Sample records for fast intracellular dynamics

  1. An in vivo model for studying the dynamics of intracellular free calcium changes in slow- and fast-twitch muscle fibres.

    Bátkai, S; Rácz, I B; Ivanics, T; Tóth, A; Hamar, J; Slaaf, D W; Reneman, R S; Ligeti, L

    1999-10-01

    The understanding of the regulation of the free cytosolic [Ca2+] ([Ca2+]i) in skeletal muscle is hampered by the lack of techniques for quantifying free [Ca2+]i in muscle fibres in situ. We describe a model for studying the dynamics of free [Ca2+]i in the fast-twitch extensor digitorum longus (EDL) and the slow-twitch soleus (SOL) muscles of the rat in vivo using caffeine superfusion to induce changes in free [Ca2+]i. We assumed that differences in sensitivity between the two muscle types for this substance reflect differences in intracellular Ca2+ handling in the fibres of which these muscles consist. The Indo-1 ratiometric method, using intravital microscopy with incident light, was adapted to measure free [Ca2+]i in vivo. Fluorescence images were collected by means of a digital camera. Caffeine superfusion at 37 degrees C for 2 min, at concentrations of 1, 2, 5, 10 or 20 mmol/l, induced a concentration-dependent increase in free [Ca2+]i and revealed differences in caffeine sensitivity between the muscle types, with the SOL being more sensitive. In a separate set of experiments the contracture threshold, as assessed by topical application of caffeine, was determined in both muscle types. EDL had a higher threshold for developing contracture than SOL. These finding are in agreement with previous in vitro studies. We may conclude that the dynamics of free [Ca2+]i can be assessed reliably in intact mammalian muscle in vivo.

  2. Dynamics of intracellular information decoding

    Kobayashi, Tetsuya J; Kamimura, Atsushi

    2011-01-01

    A variety of cellular functions are robust even to substantial intrinsic and extrinsic noise in intracellular reactions and the environment that could be strong enough to impair or limit them. In particular, of substantial importance is cellular decision-making in which a cell chooses a fate or behavior on the basis of information conveyed in noisy external signals. For robust decoding, the crucial step is filtering out the noise inevitably added during information transmission. As a minimal and optimal implementation of such an information decoding process, the autocatalytic phosphorylation and autocatalytic dephosphorylation (aPadP) cycle was recently proposed. Here, we analyze the dynamical properties of the aPadP cycle in detail. We describe the dynamical roles of the stationary and short-term responses in determining the efficiency of information decoding and clarify the optimality of the threshold value of the stationary response and its information-theoretical meaning. Furthermore, we investigate the robustness of the aPadP cycle against the receptor inactivation time and intrinsic noise. Finally, we discuss the relationship among information decoding with information-dependent actions, bet-hedging and network modularity

  3. Dynamics of intracellular information decoding.

    Kobayashi, Tetsuya J; Kamimura, Atsushi

    2011-10-01

    A variety of cellular functions are robust even to substantial intrinsic and extrinsic noise in intracellular reactions and the environment that could be strong enough to impair or limit them. In particular, of substantial importance is cellular decision-making in which a cell chooses a fate or behavior on the basis of information conveyed in noisy external signals. For robust decoding, the crucial step is filtering out the noise inevitably added during information transmission. As a minimal and optimal implementation of such an information decoding process, the autocatalytic phosphorylation and autocatalytic dephosphorylation (aPadP) cycle was recently proposed. Here, we analyze the dynamical properties of the aPadP cycle in detail. We describe the dynamical roles of the stationary and short-term responses in determining the efficiency of information decoding and clarify the optimality of the threshold value of the stationary response and its information-theoretical meaning. Furthermore, we investigate the robustness of the aPadP cycle against the receptor inactivation time and intrinsic noise. Finally, we discuss the relationship among information decoding with information-dependent actions, bet-hedging and network modularity.

  4. Dynamics of gradient formation by intracellular shuttling

    Berezhkovskii, Alexander M. [Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20892 (United States); Shvartsman, Stanislav Y. [Department of Chemical and Biological Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544 (United States)

    2015-08-21

    A number of important cellular functions rely on the formation of intracellular protein concentration gradients. Experimental studies discovered a number of mechanisms for the formation of such gradients. One of the mechanisms relies on the intracellular shuttling of a protein that interconverts between the two states with different diffusivities, under the action of two enzymes, one of which is localized to the plasma membrane, whereas the second is uniformly distributed in the cytoplasm. Recent work reported an analytical solution for the steady state gradient in this mechanism, obtained in the framework of a one-dimensional reaction-diffusion model. Here, we study the dynamics in this model and derive analytical expressions for the Laplace transforms of the time-dependent concentration profiles in terms of elementary transcendental functions. Inverting these transforms numerically, one can obtain time-dependent concentration profiles of the two forms of the protein.

  5. CONTRIBUTIONS OF INTRACELLULAR IONS TO Kv CHANNEL VOLTAGE SENSOR DYNAMICS.

    Samuel eGoodchild

    2012-06-01

    Full Text Available Voltage sensing domains of Kv channels control ionic conductance through coupling of the movement of charged residues in the S4 segment to conformational changes at the cytoplasmic region of the pore domain, that allow K+ ions to flow. Conformational transitions within the voltage sensing domain caused by changes in the applied voltage across the membrane field are coupled to the conducting pore region and the gating of ionic conductance. However, several other factors not directly linked to the voltage dependent movement of charged residues within the voltage sensor impact the dynamics of the voltage sensor, such as inactivation, ionic conductance, intracellular ion identity and block of the channel by intracellular ligands. The effect of intracellular ions on voltage sensor dynamics is of importance in the interpretation of gating current measurements and the physiology of pore/voltage sensor coupling. There is a significant amount of variability in the reported kinetics of voltage sensor deactivation kinetics of Kv channels attributed to different mechanisms such as open state stabilization, immobilization and relaxation processes of the voltage sensor. Here we separate these factors and focus on the causal role that intracellular ions can play in allosterically modulating the dynamics of Kv voltage sensor deactivation kinetics. These considerations are of critical importance in understanding the molecular determinants of the complete channel gating cycle from activation to deactivation.

  6. Estimating the biophysical properties of neurons with intracellular calcium dynamics.

    Ye, Jingxin; Rozdeba, Paul J; Morone, Uriel I; Daou, Arij; Abarbanel, Henry D I

    2014-06-01

    We investigate the dynamics of a conductance-based neuron model coupled to a model of intracellular calcium uptake and release by the endoplasmic reticulum. The intracellular calcium dynamics occur on a time scale that is orders of magnitude slower than voltage spiking behavior. Coupling these mechanisms sets the stage for the appearance of chaotic dynamics, which we observe within certain ranges of model parameter values. We then explore the question of whether one can, using observed voltage data alone, estimate the states and parameters of the voltage plus calcium (V+Ca) dynamics model. We find the answer is negative. Indeed, we show that voltage plus another observed quantity must be known to allow the estimation to be accurate. We show that observing both the voltage time course V(t) and the intracellular Ca time course will permit accurate estimation, and from the estimated model state, accurate prediction after observations are completed. This sets the stage for how one will be able to use a more detailed model of V+Ca dynamics in neuron activity in the analysis of experimental data on individual neurons as well as functional networks in which the nodes (neurons) have these biophysical properties.

  7. Decoherence recuperating fast environmental dynamics

    Cetinbas, Murat

    2010-01-01

    We examine the exact internal decoherence dynamics of a qubit in an isolated Josephson charge-qubit quantum computer in the presence of one- and two-body static internal imperfections. By help of open system dynamics quantifiers, i.e. purity, fidelity, covariance and Loschmidt echo, we distinguish between non-unitary and unitary components of internal decoherence dynamics and show that the non-unitary component consists of two processes: system-environment entanglement and incoherence. Our results indicate that the incoherence process is the major source of internal decoherence rather than system-environment entanglement. We find that strong one-body intra-environmental interactions, which generate fast environmental dynamics, result in a rapid suppression of decoherence induced by both system-environment entanglement and incoherence processes. We explain the mechanisms of suppression of decoherence for these two processes and discuss our results.

  8. Calibration and quantification of fast intracellular motion (FIM) in living cells using correlation analysis

    Veselý, Pavel; Mikš, A.; Novák, J.; Boyde, A.

    2003-01-01

    Roč. 25, - (2003), s. 230-239 ISSN 0161-0457 R&D Projects: GA ČR GA304/99/0368 Institutional research plan: CEZ:AV0Z5052915 Keywords : fast intracellular motion * living cell ů video rate confocal laser scanning microscopy Subject RIV: EA - Cell Biology Impact factor: 0.733, year: 2003

  9. Impact of intracellular metallothionein on metal biouptake and partitioning dynamics at bacterial interfaces.

    Présent, Romain M; Rotureau, Elise; Billard, Patrick; Pagnout, Christophe; Sohm, Bénédicte; Flayac, Justine; Gley, Renaud; Pinheiro, José P; Duval, Jérôme F L

    2017-11-08

    Genetically engineered microorganisms are alternatives to physicochemical methods for remediation of metal-contaminated aquifers due to their remarkable bioaccumulation capacities. The design of such biosystems would benefit from the elaboration of a sound quantitative connection between performance in terms of metal removal from aqueous solution and dynamics of the multiscale processes leading to metal biouptake. In this work, this elaboration is reported for Escherichia coli cells modified to overexpress intracellular metallothionein (MTc), a strong proteinaceous metal chelator. Depletion kinetics of Cd(ii) from bulk solution following biouptake and intracellular accumulation is addressed as a function of cell volume fraction using electroanalytical probes and ligand exchange-based analyses. It is shown that metal biouptake in the absence and presence of MTc is successfully interpreted on the basis of a formalism recently developed for metal partitioning dynamics at biointerfaces with integration of intracellular metal speciation. The analysis demonstrates how fast sequestration of metals by intracellular MTc bypasses metal excretion (efflux) and enhances the rate of metal depletion to an extent such that complete removal is achieved at sufficiently large cell volume fractions. The magnitude of the stability constant of nanoparticulate metal-MTc complexes, as derived from refined analysis of macroscopic bulk metal depletion data, is further confirmed by independent electrochemical measurement of metal binding by purified MTc extracts.

  10. Cell fate reprogramming by control of intracellular network dynamics

    Zanudo, Jorge G. T.; Albert, Reka

    Identifying control strategies for biological networks is paramount for practical applications that involve reprogramming a cell's fate, such as disease therapeutics and stem cell reprogramming. Although the topic of controlling the dynamics of a system has a long history in control theory, most of this work is not directly applicable to intracellular networks. Here we present a network control method that integrates the structural and functional information available for intracellular networks to predict control targets. Formulated in a logical dynamic scheme, our control method takes advantage of certain function-dependent network components and their relation to steady states in order to identify control targets, which are guaranteed to drive any initial state to the target state with 100% effectiveness and need to be applied only transiently for the system to reach and stay in the desired state. We illustrate our method's potential to find intervention targets for cancer treatment and cell differentiation by applying it to a leukemia signaling network and to the network controlling the differentiation of T cells. We find that the predicted control targets are effective in a broad dynamic framework. Moreover, several of the predicted interventions are supported by experiments. This work was supported by NSF Grant PHY 1205840.

  11. Collective Dynamics of Intracellular Water in Living Cells

    Orecchini, A; Sebastiani, F; Paciaroni, A; Petrillo, C; Sacchetti, F; Jasnin, M; Francesco, A De; Zaccai, G; Moulin, M; Haertlein, M

    2012-01-01

    Water dynamics plays a fundamental role for the fulfillment of biological functions in living organisms. Decades of hydrated protein powder studies have revealed the peculiar dynamical properties of hydration water with respect to pure water, due to close coupling interactions with the macromolecule. In such a framework, we have studied coherent collective dynamics in protein and DNA hydration water. State-of-the-art neutron instrumentation has allowed us to observe the propagation of coherent density fluctuations within the hydration shell of the biomolecules. The corresponding dispersion curves resulted to be only slightly affected by the coupling with the macromolecules. Nevertheless, the effects of the interaction appeared as a marked increase of the mode damping factors, which suggested a destructuring of the water hydrogen-bond network. Such results were interpreted as the signature of a 'glassy' dynamical character of macromolecule hydration water, in agreement with indications from measurements of the density of vibrational states. Extending the investigations to living organisms at physiological conditions, we present here an in-vivo study of collective dynamics of intracellular water in Escherichia coli cells. The cells and water were fully deuterated to minimise the incoherent neutron scattering background. The water dynamics observed in the living cells is discussed in terms of the dynamics of pure bulk water and that of hydration water measured in powder samples.

  12. Distributed and dynamic intracellular organization of extracellular information.

    Granados, Alejandro A; Pietsch, Julian M J; Cepeda-Humerez, Sarah A; Farquhar, Iseabail L; Tkačik, Gašper; Swain, Peter S

    2018-06-05

    Although cells respond specifically to environments, how environmental identity is encoded intracellularly is not understood. Here, we study this organization of information in budding yeast by estimating the mutual information between environmental transitions and the dynamics of nuclear translocation for 10 transcription factors. Our method of estimation is general, scalable, and based on decoding from single cells. The dynamics of the transcription factors are necessary to encode the highest amounts of extracellular information, and we show that information is transduced through two channels: Generalists (Msn2/4, Tod6 and Dot6, Maf1, and Sfp1) can encode the nature of multiple stresses, but only if stress is high; specialists (Hog1, Yap1, and Mig1/2) encode one particular stress, but do so more quickly and for a wider range of magnitudes. In particular, Dot6 encodes almost as much information as Msn2, the master regulator of the environmental stress response. Each transcription factor reports differently, and it is only their collective behavior that distinguishes between multiple environmental states. Changes in the dynamics of the localization of transcription factors thus constitute a precise, distributed internal representation of extracellular change. We predict that such multidimensional representations are common in cellular decision-making.

  13. Development of growth rate measuring method for intracellular, parasitic acid-fast bacteria using radioisotopes

    Nakata, Noboru; Fukutomi, Yasuo

    1998-01-01

    To prevent and treat infections diseases caused by pathogenic acid-fast bacteria such as Mycobacterium leprae, Tubercle bacillus, it is important to elucidate the mechanisms of intracellular proliferations of these bacteria. This research project was started to make DNA library using a new constructed shuttle vector. Development of in vitro evaluation method for intracellular proliferation of mycobacterium and its transformed cells was attempted on the basis of Buddemeyer method. This method was able to precisely determine the metabolic activities as low as those in leprae and its modified method using 14 C-palmitic acid was highly sensitive and the results were obtainable in a shorter period. The generated CO 2 was satisfactorily absorbed into scintillator without using a filter paper. A new culture medium from which arginine, a NO-producing compound was eliminated was used to repress the sterilizing effects of NO, but the metabolic activities of leprae was not enhanced. (M.N.)

  14. Development of growth rate measuring method for intracellular, parasitic acid-fast bacteria using radioisotopes

    Nakata, Noboru; Fukutomi, Yasuo [National Inst. of Infectious Deseases, Tokyo (Japan)

    1998-02-01

    To prevent and treat infections diseases caused by pathogenic acid-fast bacteria such as Mycobacterium leprae, Tubercle bacillus, it is important to elucidate the mechanisms of intracellular proliferations of these bacteria. This research project was started to make DNA library using a new constructed shuttle vector. Development of in vitro evaluation method for intracellular proliferation of mycobacterium and its transformed cells was attempted on the basis of Buddemeyer method. This method was able to precisely determine the metabolic activities as low as those in leprae and its modified method using {sup 14}C-palmitic acid was highly sensitive and the results were obtainable in a shorter period. The generated CO{sub 2} was satisfactorily absorbed into scintillator without using a filter paper. A new culture medium from which arginine, a NO-producing compound was eliminated was used to repress the sterilizing effects of NO, but the metabolic activities of leprae was not enhanced. (M.N.)

  15. Monitoring intracellular oxidative events using dynamic spectral unmixing microscopy

    There is increasing interest in using live-cell imaging to monitor not just individual intracellular endpoints, but to investigate the interplay between multiple molecular events as they unfold in real time within the cell. A major impediment to simultaneous acquisition of multip...

  16. Dynamics of postirradiation intracellular cysteine and aspartic proteinases profiles in proliferating and nonproliferating mammalian cells

    Korbelik, M.; Osmak, M.; Suhar, A.; Turk, V.; Skrk, J.

    1990-01-01

    Dynamics of postirradiation intracellular cysteine and aspartic proteinases profiles were examined in proliferating and nonproliferating Chinese hamster fibroblasts (V 79). The results show that there are significant alterations in cysteine and aspartic intracellular proteinases activity already in the early postirradiation period, which are different in proliferating and nonproliferating cells. Irradiation of the cells examined to low doses and up to 15 Gy induced an increase in cysteine proteinases activity in the early postexposure period, while at higher irradiation doses applied, the activity of these proteinases was decreased. These observations suggest that intracellular proteinases are actively participating in process involving recovery from radiation injury or cell killing. (orig.) [de

  17. The intracellular cholesterol landscape: dynamic integrator of the immune response

    Fessler, Michael B.

    2016-01-01

    Cholesterol has typically been considered an exogenous, disease-related factor in immunity; however, recent literature suggests that a paradigm shift is in order. Sterols are now recognized to ligate several immune receptors. Altered flux through the mevalonic acid synthesis pathway also appears to be a required event in the antiviral interferon response of macrophages and in the activation, proliferation, and differentiation of T cells. In this review, evidence is discussed that suggests an intrinsic, ‘professional’ role for sterols and oxysterols in macrophage and T cell immunity. Host defense may have been the original selection pressure behind the development of mechanisms for intracellular cholesterol homeostasis. Functional coupling between sterol metabolism and immunity has fundamental implications for health and disease. PMID:27692616

  18. Intracellular Transport and Kinesin Superfamily Proteins: Structure, Function and Dynamics

    Hirokawa, N.; Takemura, R.

    Using various molecular cell biological and molecular genetic approaches, we identified kinesin superfamily proteins (KIFs) and characterized their significant functions in intracellular transport, which is fundamental for cellular morphogenesis, functioning, and survival. We showed that KIFs not only transport various membranous organelles, proteins complexes and mRNAs fundamental for cellular functions but also play significant roles in higher brain functions such as memory and learning, determination of important developmental processes such as left-right asymmetry formation and brain wiring. We also elucidated that KIFs recognize and bind to their specific cargoes using scaffolding or adaptor protein complexes. Concerning the mechanism of motility, we discovered the simplest unique monomeric motor KIF1A and determined by molecular biophysics, cryoelectron microscopy and X-ray crystallography that KIF1A can move on a microtubule processively as a monomer by biased Brownian motion and by hydolyzing ATP.

  19. Dynamics of an HBV/HCV infection model with intracellular delay and cell proliferation

    Zhang, Fengqin; Li, Jianquan; Zheng, Chongwu; Wang, Lin

    2017-01-01

    A new mathematical model of hepatitis B/C virus (HBV/HCV) infection which incorporates the proliferation of healthy hepatocyte cells and the latent period of infected hepatocyte cells is proposed and studied. The dynamics is analyzed via Pontryagin's method and a newly proposed alternative geometric stability switch criterion. Sharp conditions ensuring stability of the infection persistent equilibrium are derived by applying Pontryagin's method. Using the intracellular delay as the bifurcation parameter and applying an alternative geometric stability switch criterion, we show that the HBV/HCV infection model undergoes stability switches. Furthermore, numerical simulations illustrate that the intracellular delay can induce complex dynamics such as persistence bubbles and chaos.

  20. Geometrical shock dynamics for magnetohydrodynamic fast shocks

    Mostert, W.; Pullin, D. I.; Samtaney, Ravi; Wheatley, V.

    2016-01-01

    We describe a formulation of two-dimensional geometrical shock dynamics (GSD) suitable for ideal magnetohydrodynamic (MHD) fast shocks under magnetic fields of general strength and orientation. The resulting area–Mach-number–shock-angle relation is then incorporated into a numerical method using pseudospectral differentiation. The MHD-GSD model is verified by comparison with results from nonlinear finite-volume solution of the complete ideal MHD equations applied to a shock implosion flow in the presence of an oblique and spatially varying magnetic field ahead of the shock. Results from application of the MHD-GSD equations to the stability of fast MHD shocks in two dimensions are presented. It is shown that the time to formation of triple points for both perturbed MHD and gas-dynamic shocks increases as (Formula presented.), where (Formula presented.) is a measure of the initial Mach-number perturbation. Symmetry breaking in the MHD case is demonstrated. In cylindrical converging geometry, in the presence of an azimuthal field produced by a line current, the MHD shock behaves in the mean as in Pullin et al. (Phys. Fluids, vol. 26, 2014, 097103), but suffers a greater relative pressure fluctuation along the shock than the gas-dynamic shock. © 2016 Cambridge University Press

  1. Geometrical shock dynamics for magnetohydrodynamic fast shocks

    Mostert, W.

    2016-12-12

    We describe a formulation of two-dimensional geometrical shock dynamics (GSD) suitable for ideal magnetohydrodynamic (MHD) fast shocks under magnetic fields of general strength and orientation. The resulting area–Mach-number–shock-angle relation is then incorporated into a numerical method using pseudospectral differentiation. The MHD-GSD model is verified by comparison with results from nonlinear finite-volume solution of the complete ideal MHD equations applied to a shock implosion flow in the presence of an oblique and spatially varying magnetic field ahead of the shock. Results from application of the MHD-GSD equations to the stability of fast MHD shocks in two dimensions are presented. It is shown that the time to formation of triple points for both perturbed MHD and gas-dynamic shocks increases as (Formula presented.), where (Formula presented.) is a measure of the initial Mach-number perturbation. Symmetry breaking in the MHD case is demonstrated. In cylindrical converging geometry, in the presence of an azimuthal field produced by a line current, the MHD shock behaves in the mean as in Pullin et al. (Phys. Fluids, vol. 26, 2014, 097103), but suffers a greater relative pressure fluctuation along the shock than the gas-dynamic shock. © 2016 Cambridge University Press

  2. Dynamics of fast ions in Tokamaks

    Helander, P.

    1994-01-01

    Fast ions play a prominent role in the heating of tokamak plasmas by, e.g. neutral-beam injection, ion-cyclotron-resonance heating, and alpha-particle heating. In this thesis, a number of physical and mathematical problems concerning the dynamics of fast ions in tokamaks are addressed. First, the motion under adiabatic perturbations is studied. The frequencies of instabilities excited in tokamaks sometimes vary slowly with time. The existence of an adiabatic invariant of particle motion in such circumstances is shown to lead to a rapid convection of particles in the radial direction. Generalized adiabatic invariants are constructed for systems where the slowly varying parameter is subjected to small, but rapidly varying, fluctuations. Second, the onset of stochastic motion under resonant perturbations is considered. It is shown that the finite width of fast-ion drift orbits significantly affects the threshold for stochastic motion caused by magnetic field ripple or ion-cyclotron-resonance heating. Finite-orbit-width effects are also shown to reduce the strength of resonant interaction between alpha particles and internal kink modes. Third, the diffusive motion in the stochastic regime is analysed mathematically. Monte Carlo operators for the motion on long time-scales are constructed, and the validity of the quasilinear diffusion coefficient is examined. Finally, the effects of close ion collisions are investigated. It is demonstrated that close encounters with fast ions produce a high-energy tail in the distribution functions of impurity ions, and that close collisions between fusion-generated alpha particles give rise to a population of such particles with energies extending up to twice the birth energy. 44 refs

  3. Tight Coupling of Metabolic Oscillations and Intracellular Water Dynamics in Saccharomyces cerevisiae

    Thoke, Henrik Seir; Tobiesen, Asger; Brewer, Jonathan R.

    2015-01-01

    We detected very strong coupling between the oscillating concentration of ATP and the dynamics of intracellular water during glycolysis in Saccharomyces cerevisiae. Our results indicate that: i) dipolar relaxation of intracellular water is heterogeneous within the cell and different from dilute...... conditions, ii) water dipolar relaxation oscillates with glycolysis and in phase with ATP concentration, iii) this phenomenon is scale-invariant from the subcellular to the ensemble of synchronized cells and, iv) the periodicity of both glycolytic oscillations and dipolar relaxation are equally affected by D...

  4. The Living Cell as a Multi-agent Organisation: A Compositional Organisation Model of Intracellular Dynamics

    Jonker, C. M.; Snoep, J. L.; Treur, J.; Westerhoff, H. V.; Wijngaards, W. C. A.

    Within the areas of Computational Organisation Theory and Artificial Intelligence, techniques have been developed to simulate and analyse dynamics within organisations in society. Usually these modelling techniques are applied to factories and to the internal organisation of their process flows, thus obtaining models of complex organisations at various levels of aggregation. The dynamics in living cells are often interpreted in terms of well-organised processes, a bacterium being considered a (micro)factory. This suggests that organisation modelling techniques may also benefit their analysis. Using the example of Escherichia coli it is shown how indeed agent-based organisational modelling techniques can be used to simulate and analyse E.coli's intracellular dynamics. Exploiting the abstraction levels entailed by this perspective, a concise model is obtained that is readily simulated and analysed at the various levels of aggregation, yet shows the cell's essential dynamic patterns.

  5. Light-induced dynamic structural color by intracellular 3D photonic crystals in brown algae.

    Lopez-Garcia, Martin; Masters, Nathan; O'Brien, Heath E; Lennon, Joseph; Atkinson, George; Cryan, Martin J; Oulton, Ruth; Whitney, Heather M

    2018-04-01

    Natural photonic crystals are responsible for strong reflectance at selective wavelengths in different natural systems. We demonstrate that intracellular opal-like photonic crystals formed from lipids within photosynthetic cells produce vivid structural color in the alga Cystoseira tamariscifolia . The reflectance of the opaline vesicles is dynamically responsive to environmental illumination. The structural color is present in low light-adapted samples, whereas higher light levels produce a slow disappearance of the structural color such that it eventually vanishes completely. Once returned to low-light conditions, the color re-emerges. Our results suggest that these complex intracellular natural photonic crystals are responsive to environmental conditions, changing their packing structure reversibly, and have the potential to manipulate light for roles beyond visual signaling.

  6. Change detection in the dynamics of an intracellular protein synthesis model using nonlinear Kalman filtering.

    Rigatos, Gerasimos G; Rigatou, Efthymia G; Djida, Jean Daniel

    2015-10-01

    A method for early diagnosis of parametric changes in intracellular protein synthesis models (e.g. the p53 protein - mdm2 inhibitor model) is developed with the use of a nonlinear Kalman Filtering approach (Derivative-free nonlinear Kalman Filter) and of statistical change detection methods. The intracellular protein synthesis dynamic model is described by a set of coupled nonlinear differential equations. It is shown that such a dynamical system satisfies differential flatness properties and this allows to transform it, through a change of variables (diffeomorphism), to the so-called linear canonical form. For the linearized equivalent of the dynamical system, state estimation can be performed using the Kalman Filter recursion. Moreover, by applying an inverse transformation based on the previous diffeomorphism it becomes also possible to obtain estimates of the state variables of the initial nonlinear model. By comparing the output of the Kalman Filter (which is assumed to correspond to the undistorted dynamical model) with measurements obtained from the monitored protein synthesis system, a sequence of differences (residuals) is obtained. The statistical processing of the residuals with the use of x2 change detection tests, can provide indication within specific confidence intervals about parametric changes in the considered biological system and consequently indications about the appearance of specific diseases (e.g. malignancies).

  7. Tissue architecture and function: dynamic reciprocity via extra- and intra-cellular matrices

    Xu, Ren; Boudreau, Aaron; Bissell, Mina J

    2008-12-23

    Mammary gland development, functional differentiation, and homeostasis are orchestrated and sustained by a balance of biochemical and biophysical cues from the organ's microenvironment. The three-dimensional microenvironment of the mammary gland, predominantly 'encoded' by a collaboration between the extracellular matrix (ECM), hormones, and growth factors, sends signals from ECM receptors through the cytoskeletal intracellular matrix to nuclear and chromatin structures resulting in gene expression; the ECM in turn is regulated and remodeled by signals from the nucleus. In this chapter, we discuss how coordinated ECM deposition and remodeling is necessary for mammary gland development, how the ECM provides structural and biochemical cues necessary for tissue-specific function, and the role of the cytoskeleton in mediating the extra - to intracellular dialogue occurring between the nucleus and the microenvironment. When operating normally, the cytoskeletal-mediated dynamic and reciprocal integration of tissue architecture and function directs mammary gland development, tissue polarity, and ultimately, tissue-specific gene expression. Cancer occurs when these dynamic interactions go awry for an extended time.

  8. 3D Spatially Resolved Models of the Intracellular Dynamics of the Hepatitis C Genome Replication Cycle

    Knodel, Markus

    2017-10-02

    Mathematical models of virus dynamics have not previously acknowledged spatial resolution at the intracellular level despite substantial arguments that favor the consideration of intracellular spatial dependence. The replication of the hepatitis C virus (HCV) viral RNA (vRNA) occurs within special replication complexes formed from membranes derived from endoplasmatic reticulum (ER). These regions, termed membranous webs, are generated primarily through specific interactions between nonstructural virus-encoded proteins (NSPs) and host cellular factors. The NSPs are responsible for the replication of the vRNA and their movement is restricted to the ER surface. Therefore, in this study we developed fully spatio-temporal resolved models of the vRNA replication cycle of HCV. Our simulations are performed upon realistic reconstructed cell structures-namely the ER surface and the membranous webs-based on data derived from immunostained cells replicating HCV vRNA. We visualized 3D simulations that reproduced dynamics resulting from interplay of the different components of our models (vRNA, NSPs, and a host factor), and we present an evaluation of the concentrations for the components within different regions of the cell. Thus far, our model is restricted to an internal portion of a hepatocyte and is qualitative more than quantitative. For a quantitative adaption to complete cells, various additional parameters will have to be determined through further in vitro cell biology experiments, which can be stimulated by the results deccribed in the present study.

  9. Development of a method to measure intracellular growth rate of parasitic acid-fast bacteria using radio-isotope and its improvement

    Nakata, Noboru; Fukutomi, Yasuo

    1999-01-01

    Development of measurement method for intracellular growth rate was attempted using gene-transfected acid-fast bacteria and Mycobacterium leprae. M. leprae was inoculated into a well, which was filled with fetus bovine serum containing a cover slip pasted with mouse monocyte-derived malignant cell lines, J774 and P388D1 and cultured for 3-4 hours. Then, the cells on the cover slip were mobilized with 0.1 N NaOH. The metabolic activity of M. leprae was assessed based on the β-oxidation activity of 14 C-palmitic acid. Then, it was investigated whether TNF is produced by the cell culture added with M. leprae or LPS. J774 cells abundantly produced TNF after sensitization with LPS and its production was depending on the amount of added bacteria, whereas TNF production after sensitization with LPS or M. leprae was little in P388D1 cells. Staining for acid-fast bacteria revealed that either of these cell lines has phagocytic activity for M. leprae. To identify the bacterial factor involved to the intracellular proliferation of acid-fast bacteria, transposon insertion mutagenesis was attempted to M. avium complex (MAC) and the degrees of drug-resistance in M. avium mino, M. intracellulare JATA-52 and 8 clinically isolated M. intracellulare strains were determined. M. intracellulare JATA-52 was resistant to kanamycin and plasmid pAL8 and pYT937 were both able to transform the strain with dose-dependency. Since M. intracellulare is pathogenic to human and the strain proliferates with a generation time shorter than that of M. tuberculosis, the former strain is thought suitable for the analysis of a mutated gene. Thus, it became possible to study transposition insertion mutagenesis in M. intracellulare. (M.N.)

  10. Development of a method to measure intracellular growth rate of parasitic acid-fast bacteria using radio-isotope and its improvement

    Nakata, Noboru; Fukutomi, Yasuo [National Inst. of Infectious Diseases, Tokyo (Japan)

    1999-02-01

    Development of measurement method for intracellular growth rate was attempted using gene-transfected acid-fast bacteria and Mycobacterium leprae. M. leprae was inoculated into a well, which was filled with fetus bovine serum containing a cover slip pasted with mouse monocyte-derived malignant cell lines, J774 and P388D1 and cultured for 3-4 hours. Then, the cells on the cover slip were mobilized with 0.1 N NaOH. The metabolic activity of M. leprae was assessed based on the {beta}-oxidation activity of {sup 14}C-palmitic acid. Then, it was investigated whether TNF is produced by the cell culture added with M. leprae or LPS. J774 cells abundantly produced TNF after sensitization with LPS and its production was depending on the amount of added bacteria, whereas TNF production after sensitization with LPS or M. leprae was little in P388D1 cells. Staining for acid-fast bacteria revealed that either of these cell lines has phagocytic activity for M. leprae. To identify the bacterial factor involved to the intracellular proliferation of acid-fast bacteria, transposon insertion mutagenesis was attempted to M. avium complex (MAC) and the degrees of drug-resistance in M. avium mino, M. intracellulare JATA-52 and 8 clinically isolated M. intracellulare strains were determined. M. intracellulare JATA-52 was resistant to kanamycin and plasmid pAL8 and pYT937 were both able to transform the strain with dose-dependency. Since M. intracellulare is pathogenic to human and the strain proliferates with a generation time shorter than that of M. tuberculosis, the former strain is thought suitable for the analysis of a mutated gene. Thus, it became possible to study transposition insertion mutagenesis in M. intracellulare. (M.N.)

  11. A fast dynamic mode in rare earth based glasses

    Zhao, L. Z.; Xue, R. J.; Zhu, Z. G.; Wang, W. H.; Bai, H. Y., E-mail: hybai@iphy.ac.cn [Institute of Physics, Chinese Academy of Sciences, Beijing 100190 (China); Ngai, K. L. [Dipartimento di Fisica, Università di Pisa, Largo B. Pontecorvo 3, I-56127 Pisa (Italy)

    2016-05-28

    Metallic glasses (MGs) usually exhibit only slow β-relaxation peak, and the signature of the fast dynamic is challenging to be observed experimentally in MGs. We report a general and unusual fast dynamic mode in a series of rare earth based MGs manifested as a distinct fast β′-relaxation peak in addition to slow β-relaxation and α-relaxation peaks. We show that the activation energy of the fast β′-relaxation is about 12RT{sub g} and is equivalent to the activation of localized flow event. The coupling of these dynamic processes as well as their relationship with glass transition and structural heterogeneity is discussed.

  12. Control of local intracellular calcium concentration with dynamic-clamp controlled 2-photon uncaging.

    Erwin Idoux

    Full Text Available The variations of the intracellular concentration of calcium ion ([Ca(2+](i are at the heart of intracellular signaling, and their imaging is therefore of enormous interest. However, passive [Ca(2+](i imaging provides no control over these variations, meaning that a full exploration of the functional consequences of [Ca(2+](i changes is difficult to attain. The tools designed so far to modify [Ca(2+](i, even qualitatively, suffer drawbacks that undermine their widespread use. Here, we describe an electro-optical technique to quantitatively set [Ca(2+](i, in real time and with sub-cellular resolution, using two-photon Ca(2+ uncaging and dynamic-clamp. We experimentally demonstrate, on neurons from acute olfactory bulb slices of Long Evans rats, various capabilities of this technique previously difficult to achieve, such as the independent control of the membrane potential and [Ca(2+](i variations, the functional knocking-in of user-defined virtual voltage-dependent Ca(2+ channels, and the standardization of [Ca(2+](i patterns across different cells. Our goal is to lay the groundwork for this technique and establish it as a new and versatile tool for the study of cell signaling.

  13. A Gold Nanoparticle Bio-Optical Transponder to Dynamically Monitor Intracellular pH.

    Carnevale, Kate J F; Riskowski, Ryan A; Strouse, Geoffrey F

    2018-06-13

    A pH-sensitive bio-optical transponder (pH-BOT) capable of simultaneously reporting the timing of intracellular DNA cargo release from a gold nanoparticle (AuNP) and the evolving intracellular pH (pH i) during endosomal maturation is demonstrated. The pH-BOT is designed with a triple-dye-labeled duplex DNA appended to a 6.6 nm AuNP, utilizing pH-responsive fluorescein paired with DyLight405 as a surface energy transfer (SET) coupled dye pair to ratiometrically report the pH at and after cargo release. A non-SET-coupled dye, DyLight 700, is used to provide dynamic tracking throughout the experiment. The pH-BOT beacon of the cargo uptake, release, and processing was visualized using live-cell confocal fluorescent microscopy in Chinese hamster ovary cells, and it was observed that while maturation of endosomes carrying pH-BOT is slowed significantly, the pH-BOT is distributed throughout the endolysosomal system while remaining at pH ∼6. This observed decoupling of endosomal maturation from acidification lends support to those models that propose that pH alone is not sufficient to explain endosomal maturation and may enable greater insight into our understanding of the fundamental processes of biology.

  14. Fast heuristics for a dynamic paratransit problem

    Cremers, M.L.A.G.; Klein Haneveld, W.K.; van der Vlerk, M.H.

    2008-01-01

    In a previous paper we developed a non-standard two-stage recourse model for the dynamic day-ahead paratransit planning problem. Two heuristics, which are frequently applied in the recourse model, contain many details which leads to large CPU times to solve instances of relatively small size. In

  15. FAST - A multiprocessed environment for visualization of computational fluid dynamics

    Bancroft, G.V.; Merritt, F.J.; Plessel, T.C.; Kelaita, P.G.; Mccabe, R.K.

    1991-01-01

    The paper presents the Flow Analysis Software Toolset (FAST) to be used for fluid-mechanics analysis. The design criteria for FAST including the minimization of the data path in the computational fluid-dynamics (CFD) process, consistent user interface, extensible software architecture, modularization, and the isolation of three-dimensional tasks from the application programmer are outlined. Each separate process communicates through the FAST Hub, while other modules such as FAST Central, NAS file input, CFD calculator, surface extractor and renderer, titler, tracer, and isolev might work together to generate the scene. An interprocess communication package making it possible for FAST to operate as a modular environment where resources could be shared among different machines as well as a single host is discussed. 20 refs

  16. Real time simulation method for fast breeder reactors dynamics

    Miki, Tetsushi; Mineo, Yoshiyuki; Ogino, Takamichi; Kishida, Koji; Furuichi, Kenji.

    1985-01-01

    The development of multi-purpose real time simulator models with suitable plant dynamics was made; these models can be used not only in training operators but also in designing control systems, operation sequences and many other items which must be studied for the development of new type reactors. The prototype fast breeder reactor ''Monju'' is taken as an example. Analysis is made on various factors affecting the accuracy and computer load of its dynamic simulation. A method is presented which determines the optimum number of nodes in distributed systems and time steps. The oscillations due to the numerical instability are observed in the dynamic simulation of evaporators with a small number of nodes, and a method to cancel these oscillations is proposed. It has been verified through the development of plant dynamics simulation codes that these methods can provide efficient real time dynamics models of fast breeder reactors. (author)

  17. DMPD: Intracellular DNA sensors in immunity. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 18573338 Intracellular DNA sensors in immunity. Takeshita F, Ishii KJ. Curr Opin Im...munol. 2008 Aug;20(4):383-8. Epub 2008 Jun 23. (.png) (.svg) (.html) (.csml) Show Intracellular DNA sensors ...in immunity. PubmedID 18573338 Title Intracellular DNA sensors in immunity. Authors Takeshita F, Ishii KJ. P

  18. DMPD: NOD-like receptors (NLRs): bona fide intracellular microbial sensors. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 18585455 NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Shaw...tml) (.csml) Show NOD-like receptors (NLRs): bona fide intracellular microbial sensors. PubmedID 18585455 Ti...tle NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Authors

  19. Fast Synthesis of Dynamic Colour Textures

    Filip, Jiří; Haindl, Michal; Chetverikov, D.

    -, č. 66 (2006), s. 53-54 ISSN 0926-4981 R&D Projects: GA AV ČR IAA2075302; GA AV ČR 1ET400750407; GA MŠk 1M0572 EU Projects: European Commission(XE) 507752 - MUSCLE Institutional research plan: CEZ:AV0Z10750506 Keywords : dynamic colour texture * texture synthesis * texture modelling Subject RIV: BD - Theory of Information http://www.ercim.org/publication/Ercim_News/enw66/haindl.html

  20. Fast Responding Voltage Regulator and Dynamic VAR Compensator

    Divan, Deepak [Varentec, Incorporated, San Jose, CA (United States); Moghe, Rohit [Varentec, Incorporated, San Jose, CA (United States); Tholomier, Damien [Varentec, Incorporated, San Jose, CA (United States)

    2014-12-31

    The objectives of this project were to develop a dynamic VAR compensator (DVC) for voltage regulation through VAR support to demonstrate the ability to achieve greater levels of voltage control on electricity distribution networks, and faster response compared to existing grid technology. The goal of the project was to develop a prototype Fast Dynamic VAR Compensator (Fast DVC) hardware device, and this was achieved. In addition to developing the dynamic VAR compensator device, Varentec in partnership with researchers at North Carolina State University (NCSU) successfully met the objectives to model the potential positive impact of such DVCs on representative power networks. This modeling activity validated the ability of distributed dynamic VAR compensators to provide fast voltage regulation and reactive power control required to respond to grid disturbances under high penetration of fluctuating and intermittent distributed energy resources (DERs) through extensive simulation studies. Specifically the following tasks were set to be accomplished: 1) Development of dynamic VAR compensator to support dynamic voltage variations on the grid through VAR control 2) Extensive testing of the DVC in the lab environment 3) Present the operational DVC device to the DOE at Varentec’s lab 4) Formulation of a detailed specification sheet, unit assembly document, test setup document, unit bring-up plan, and test plan 5) Extensive simulations of the DVC in a system with high PV penetration. Understanding the operation with many DVC on a single distribution system 6) Creation and submittal of quarterly and final reports conveying the design documents, unit performance data, modeling simulation charts and diagrams, and summary explanations of the satisfaction of program goals. This report details the various efforts that led to the development of the Fast DVC as well as the modeling & simulation results. The report begins with the introduction in Section II which outlines the

  1. Bat Dynamics of Female Fast Pitch Softball Batters.

    Messier, Stephen P.; Owen, Marjorie G.

    1984-01-01

    Female fast pitch softball batters served in an examination of the dynamic characteristics of the bat during the swing through the use of three-dimensional cinematographic analysis techniques. These results were compared with those from previous studies of baseball batting. Findings are listed. (Author/DF)

  2. Quantum dynamics of fast chemical reactions

    Light, J.C. [Univ. of Chicago, IL (United States)

    1993-12-01

    The aims of this research are to explore, develop, and apply theoretical methods for the evaluation of the dynamics of gas phase collision processes, primarily chemical reactions. The primary theoretical tools developed for this work have been quantum scattering theory, both in time dependent and time independent forms. Over the past several years, the authors have developed and applied methods for the direct quantum evaluation of thermal rate constants, applying these to the evaluation of the hydrogen isotopic exchange reactions, applied wave packet propagation techniques to the dissociation of Rydberg H{sub 3}, incorporated optical potentials into the evaluation of thermal rate constants, evaluated the use of optical potentials for state-to-state reaction probability evaluations, and, most recently, have developed quantum approaches for electronically non-adiabatic reactions which may be applied to simplify calculations of reactive, but electronically adiabatic systems. Evaluation of the thermal rate constants and the dissociation of H{sub 3} were reported last year, and have now been published.

  3. Analytical dynamic modeling of fast trilayer polypyrrole bending actuators

    Amiri Moghadam, Amir Ali; Moavenian, Majid; Tahani, Masoud; Torabi, Keivan

    2011-01-01

    Analytical modeling of conjugated polymer actuators with complicated electro-chemo-mechanical dynamics is an interesting area for research, due to the wide range of applications including biomimetic robots and biomedical devices. Although there have been extensive reports on modeling the electrochemical dynamics of polypyrrole (PPy) bending actuators, mechanical dynamics modeling of the actuators remains unexplored. PPy actuators can operate with low voltage while producing large displacement in comparison to robotic joints, they do not have friction or backlash, but they suffer from some disadvantages such as creep and hysteresis. In this paper, a complete analytical dynamic model for fast trilayer polypyrrole bending actuators has been proposed and named the analytical multi-domain dynamic actuator (AMDDA) model. First an electrical admittance model of the actuator will be obtained based on a distributed RC line; subsequently a proper mechanical dynamic model will be derived, based on Hamilton's principle. The purposed modeling approach will be validated based on recently published experimental results

  4. Structural dynamics in fast reactor accident analysis

    Fistedis, S.H.

    1975-01-01

    Analyses and codes are under development combining the hydrodynamics and solid mechanics (and more recently the bubble dynamics) phenomena to gage the stresses, strains, and deformations of important primary components, as well as the overall adequacy of primary and secondary containments. An arbitrary partition of the structural components treated evolves into (1) a core mechanics effort; and (2) a primary system and containment program. The primary system and containment program treats the structural response of components beyond the core, starting with the core barrel. Combined hydrodynamics-solid mechanics codes provide transient stresses and strains and final deformations for components such as the reactor vessel, reactor cover, cover holddown bolts, as well as the pulses for which the primary piping system is to be analyzed. Both, Lagrangian and Eulerian two-dimensional codes are under development, which provide greater accuracy and longer durations for the treatment of HCDA. The codes are being augmented with bubble migration capability pertaining to the latter stages of the HCDA, after slug impact. Recent developments involve the adaptation of the 2-D Eulerian primary system code to the 2-D elastic-plastic treatment of primary piping. Pulses are provided at the vessel-primary piping interfaces of the inlet and outlet nozzles, calculation includes the elbows and pressure drops along the components of the primary piping system. Recent improvements to the primary containment codes include introduction of bending strength in materials, Langrangian mesh regularization techniques, and treatment of energy absorbing materials for the slug impact. Another development involves the combination of a 2-D finite element code for the reactor cover with the hydrodynamic containment code

  5. Collisionally induced stochastic dynamics of fast ions in solids

    Burgdoerfer, J.

    1989-01-01

    Recent developments in the theory of excited state formation in collisions of fast highly charged ions with solids are reviewed. We discuss a classical transport theory employing Monte-Carlo sampling of solutions of a microscopic Langevin equation. Dynamical screening by the dielectric medium as well as multiple collisions are incorporated through the drift and stochastic forces in the Langevin equation. The close relationship between the extrinsically stochastic dynamics described by the Langevin and the intrinsic stochasticity in chaotic nonlinear dynamical systems is stressed. Comparison with experimental data and possible modification by quantum corrections are discussed. 49 refs., 11 figs

  6. Sistem Gesture Accelerometer dengan Metode Fast Dynamic Time Warping (FastDTW

    Sam Farisa Chaerul Haviana

    2016-01-01

    Full Text Available In the modern environment, the interaction between humans and computers require a more natural form of interaction. Therefore, it is important to be able to build a system that can meet these demands, such as by building a hand gesture recognition system or gesture to create a more natural form of interaction. This study aims to design a smartphone’s accelerometer gesture system as human computer interaction interfaces using FastDTW (Fast Dynamic Time Warping.The result of this study is form of gesture interaction which implemented in a system that can make the process of recognition of the human hand movements based on a smartphone accelerometer which generates a command to run the media player application functions as a case study. FastDTW as the development of Dynamic Time Warping method (DTW is able to compute faster than DTW and have an accuracy approaching DTW. From the test results, FastDTW show a fairly high degree of accuracy reached 86% and showed a better computing speed compared to DTW   Keywords: Human and Computer Interaction, Accelerometer-based gesture, FastDTW, Media player application function

  7. Focusing light through dynamical samples using fast continuous wavefront optimization.

    Blochet, B; Bourdieu, L; Gigan, S

    2017-12-01

    We describe a fast continuous optimization wavefront shaping system able to focus light through dynamic scattering media. A micro-electro-mechanical system-based spatial light modulator, a fast photodetector, and field programmable gate array electronics are combined to implement a continuous optimization of a wavefront with a single-mode optimization rate of 4.1 kHz. The system performances are demonstrated by focusing light through colloidal solutions of TiO 2 particles in glycerol with tunable temporal stability.

  8. The Role of Fast Carrier Dynamics in SOA Based Devices

    Mørk, Jesper; Berg, Tommy Winther; Nielsen, Mads Lønstrup

    2004-01-01

    and the properties of schemes relying on cross-gain as well as cross-phase modulation are discussed. The possible benefits of using SOAs with quantum dot active regions are theoretically analyzed. The bandfilling characteristics and the presence of fast capture processes may allow to reach bitrates in excess of 100......We describe the characteristics of all-optical switching schemes based on semiconductor optical amplifiers (SOAs), with particular emphasis on the role of the fast carrier dynamics. The SOA response to a single short pulse as well as to a data-modulated pulse train is investigated...

  9. Intracellular dynamics of the Hsp90 co-chaperone p23 is dictated by Hsp90

    Picard, Didier

    2006-01-01

    p23 is a component of the Hsp90 molecular chaperone machine. It binds and stabilizes the ATP-bound dimeric form of Hsp90. Since Hsp90 binds protein substrates in the ATP conformation, p23 has been proposed to stabilize Hsp90-substrate complexes. In addition, p23 can also function as a molecular chaperone by itself and even possesses an unrelated enzymatic activity. Whether it fulfills the latter functions in cells while bound to Hsp90 remains unknown and is difficult to extrapolate from cell-free biochemical experiments. Using the 'fluorescence recovery after photobleaching' (FRAP) technology, I have examined the dynamics of human p23, expressed as a fusion protein with the green fluorescent protein (GFP), in living human HeLa cells. GFP-p23 is distributed throughout the cell, and its mobility is identical in the cytoplasm and in the nucleus. When the Hsp90 interaction is disrupted either with the Hsp90 inhibitor geldanamycin or by introduction of point mutations into p23, the mobility of p23 is greatly accelerated. Under these conditions, its intracellular movement may be diffusion-controlled. In contrast, when wild-type p23 is able to bind Hsp90, a more complex FRAP behavior is observed, suggesting that it is quantitatively bound in Hsp90 complexes undergoing a multitude of other interactions

  10. pTRA - A reporter system for monitoring the intracellular dynamics of gene expression.

    Wagner, Sabine G; Ziegler, Martin; Löwe, Hannes; Kremling, Andreas; Pflüger-Grau, Katharina

    2018-01-01

    The presence of standardised tools and methods to measure and represent accurately biological parts and functions is a prerequisite for successful metabolic engineering and crucial to understand and predict the behaviour of synthetic genetic circuits. Many synthetic gene networks are based on transcriptional circuits, thus information on transcriptional and translational activity is important for understanding and fine-tuning the synthetic function. To this end, we have developed a toolkit to analyse systematically the transcriptional and translational activity of a specific synthetic part in vivo. It is based on the plasmid pTRA and allows the assignment of specific transcriptional and translational outputs to the gene(s) of interest (GOI) and to compare different genetic setups. By this, the optimal combination of transcriptional strength and translational activity can be identified. The design is tested in a case study using the gene encoding the fluorescent mCherry protein as GOI. We show the intracellular dynamics of mRNA and protein formation and discuss the potential and shortcomings of the pTRA plasmid.

  11. Intracellular localization and dynamics of Hypericin loaded PLLA nanocarriers by image correlation spectroscopy.

    Penjweini, Rozhin; Deville, Sarah; D'Olieslaeger, Lien; Berden, Mandy; Ameloot, Marcel; Ethirajan, Anitha

    2015-11-28

    The study of cell-nanoparticle interactions is an important aspect for understanding drug delivery using nanocarriers. In this regard, advances in fluorescence based microscopy are useful for the investigation of temporal and spatial behavior of nanoparticles (NPs) within the intracellular environment. In this work, we focus on the delivery of the naturally-occurring hydrophobic photosensitizer Hypericin in human lung carcinoma A549 cells by using biodegradable poly L-lactic acid NPs. For the first time, Hypericin containing NPs are prepared by combining the miniemulsion technique with the solvent evaporation method. This approach yields an efficient loading of the NPs with Hypericin and allows for additional cargo molecules. To monitor the release of Hypercin from the NPs, an additional fluorescent lipophilic dye Coumarin-6 is incorporated in the NPs. Temporal and spatiotemporal image correlation spectroscopy is used to determine the fate of the NPs carrying the potential cargo. Both directed and non-directed motions are detected. By using image cross-correlation spectroscopy and specific fluorescent labeling of endosomes, lysosomes and mitochondria, the dynamics of the cargo loaded NPs in association with the organelles is studied. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells.

    Asaph Zylbertal

    2015-12-01

    Full Text Available Persistent activity has been reported in many brain areas and is hypothesized to mediate working memory and emotional brain states and to rely upon network or biophysical feedback. Here, we demonstrate a novel mechanism by which persistent neuronal activity can be generated without feedback, relying instead on the slow removal of Na+ from neurons following bursts of activity. We show that mitral cells in the accessory olfactory bulb (AOB, which plays a major role in mammalian social behavior, may respond to a brief sensory stimulation with persistent firing. By combining electrical recordings, Ca2+ and Na+ imaging, and realistic computational modeling, we explored the mechanisms underlying the persistent activity in AOB mitral cells. We found that the exceptionally slow inward current that underlies this activity is governed by prolonged dynamics of intracellular Na+ ([Na+]i, which affects neuronal electrical activity via several pathways. Specifically, elevated dendritic [Na+]i reverses the Na+-Ca2+ exchanger activity, thus modifying the [Ca2+]i set-point. This process, which relies on ubiquitous membrane mechanisms, is likely to play a role in other neuronal types in various brain regions.

  13. Quantitative imaging of cerebral blood flow velocity and intracellular motility using dynamic light scattering-optical coherence tomography.

    Lee, Jonghwan; Radhakrishnan, Harsha; Wu, Weicheng; Daneshmand, Ali; Climov, Mihail; Ayata, Cenk; Boas, David A

    2013-06-01

    This paper describes a novel optical method for label-free quantitative imaging of cerebral blood flow (CBF) and intracellular motility (IM) in the rodent cerebral cortex. This method is based on a technique that integrates dynamic light scattering (DLS) and optical coherence tomography (OCT), named DLS-OCT. The technique measures both the axial and transverse velocities of CBF, whereas conventional Doppler OCT measures only the axial one. In addition, the technique produces a three-dimensional map of the diffusion coefficient quantifying nontranslational motions. In the DLS-OCT diffusion map, we observed high-diffusion spots, whose locations highly correspond to neuronal cell bodies and whose diffusion coefficient agreed with that of the motion of intracellular organelles reported in vitro in the literature. Therefore, the present method has enabled, for the first time to our knowledge, label-free imaging of the diffusion-like motion of intracellular organelles in vivo. As an example application, we used the method to monitor CBF and IM during a brief ischemic stroke, where we observed an induced persistent reduction in IM despite the recovery of CBF after stroke. This result supports that the IM measured in this study represent the cellular energy metabolism-related active motion of intracellular organelles rather than free diffusion of intracellular macromolecules.

  14. Linear Dynamics Model for Steam Cooled Fast Power Reactors

    Vollmer, H

    1968-04-15

    A linear analytical dynamic model is developed for steam cooled fast power reactors. All main components of such a plant are investigated on a general though relatively simple basis. The model is distributed in those parts concerning the core but lumped as to the external plant components. Coolant is considered as compressible and treated by the actual steam law. Combined use of analogue and digital computer seems most attractive.

  15. Fast and Cache-Oblivious Dynamic Programming with Local Dependencies

    Bille, Philip; Stöckel, Morten

    2012-01-01

    are widely used in bioinformatics to compare DNA and protein sequences. These problems can all be solved using essentially the same dynamic programming scheme over a two-dimensional matrix, where each entry depends locally on at most 3 neighboring entries. We present a simple, fast, and cache......-oblivious algorithm for this type of local dynamic programming suitable for comparing large-scale strings. Our algorithm outperforms the previous state-of-the-art solutions. Surprisingly, our new simple algorithm is competitive with a complicated, optimized, and tuned implementation of the best cache-aware algorithm...

  16. Fast dynamics perturbation analysis for prediction of protein functional sites

    Cohn Judith D

    2008-01-01

    Full Text Available Abstract Background We present a fast version of the dynamics perturbation analysis (DPA algorithm to predict functional sites in protein structures. The original DPA algorithm finds regions in proteins where interactions cause a large change in the protein conformational distribution, as measured using the relative entropy Dx. Such regions are associated with functional sites. Results The Fast DPA algorithm, which accelerates DPA calculations, is motivated by an empirical observation that Dx in a normal-modes model is highly correlated with an entropic term that only depends on the eigenvalues of the normal modes. The eigenvalues are accurately estimated using first-order perturbation theory, resulting in a N-fold reduction in the overall computational requirements of the algorithm, where N is the number of residues in the protein. The performance of the original and Fast DPA algorithms was compared using protein structures from a standard small-molecule docking test set. For nominal implementations of each algorithm, top-ranked Fast DPA predictions overlapped the true binding site 94% of the time, compared to 87% of the time for original DPA. In addition, per-protein recall statistics (fraction of binding-site residues that are among predicted residues were slightly better for Fast DPA. On the other hand, per-protein precision statistics (fraction of predicted residues that are among binding-site residues were slightly better using original DPA. Overall, the performance of Fast DPA in predicting ligand-binding-site residues was comparable to that of the original DPA algorithm. Conclusion Compared to the original DPA algorithm, the decreased run time with comparable performance makes Fast DPA well-suited for implementation on a web server and for high-throughput analysis.

  17. A note on the theory of fast money flow dynamics

    Sokolov, A.; Kieu, T.; Melatos, A.

    2010-08-01

    The gauge theory of arbitrage was introduced by Ilinski in [K. Ilinski, preprint arXiv:hep-th/9710148 (1997)] and applied to fast money flows in [A. Ilinskaia, K. Ilinski, preprint arXiv:cond-mat/9902044 (1999); K. Ilinski, Physics of finance: gauge modelling in non-equilibrium pricing (Wiley, 2001)]. The theory of fast money flow dynamics attempts to model the evolution of currency exchange rates and stock prices on short, e.g. intra-day, time scales. It has been used to explain some of the heuristic trading rules, known as technical analysis, that are used by professional traders in the equity and foreign exchange markets. A critique of some of the underlying assumptions of the gauge theory of arbitrage was presented by Sornette in [D. Sornette, Int. J. Mod. Phys. C 9, 505 (1998)]. In this paper, we present a critique of the theory of fast money flow dynamics, which was not examined by Sornette. We demonstrate that the choice of the input parameters used in [K. Ilinski, Physics of finance: gauge modelling in non-equilibrium pricing (Wiley, 2001)] results in sinusoidal oscillations of the exchange rate, in conflict with the results presented in [K. Ilinski, Physics of finance: gauge modelling in non-equilibrium pricing (Wiley, 2001)]. We also find that the dynamics predicted by the theory are generally unstable in most realistic situations, with the exchange rate tending to zero or infinity exponentially.

  18. Dynamics of inorganic nutrients in intertidal sediments: porewater, exchangeable and intracellular pools

    Emilio eGarcia-Robledo

    2016-05-01

    Full Text Available The study of inorganic nutrients dynamics in shallow sediments usually focuses on two main pools: the porewater (PW nutrients and the exchangeable (EX ammonium and phosphate. Recently, it has been found that microphytobenthos (MPB and other microorganisms can accumulate large amounts of nutrients intracellularly (IC, highlighting the biogeochemical importance of this nutrient pool. Storing nutrients could support the growth of autotrophs when nutrients are not available, and could also provide alternative electron acceptors for dissimilatory processes such as nitrate reduction. Here, we studied the magnitude and relative importance of these three nutrient pools (PW, IC and EX and their relation to chlorophylls (used as a proxy for MPB abundance and organic matter (OM contents in an intertidal mudflat of Cadiz Bay (Spain. MPB was localized in the first 4 mm of the sediment and showed a clear seasonal pattern; highest chlorophylls content was found during autumn and lowest during spring-summer. The temporal and spatial distribution of nutrients pools and MPB were largely correlated. Ammonium was higher in the IC and EX fractions, representing on average 59 and 37% of the total ammonium pool, respectively. Similarly, phosphate in the IC and EX fractions accounted on average for 40 and 31% of the total phosphate pool, respectively. Nitrate in the PW was low, suggesting low nitrification activity and rapid consumption. Nitrate accumulated in the IC pool during periods of moderate MPB abundance, being up to 66% of the total nitrate pool, whereas it decreased when chlorophyll concentration peaked likely due to a high nitrogen demand. EX-Nitrate accounted for the largest fraction of total sediment nitrate, 66% on average. The distribution of EX-Nitrate was significantly correlated with chlorophyll and OM, which probably indicates a relation of this pool to an increased availability of sites for ionic adsorption. This EX-Nitrate pool could represent an

  19. Overview of fast algorithm in 3D dynamic holographic display

    Liu, Juan; Jia, Jia; Pan, Yijie; Wang, Yongtian

    2013-08-01

    3D dynamic holographic display is one of the most attractive techniques for achieving real 3D vision with full depth cue without any extra devices. However, huge 3D information and data should be preceded and be computed in real time for generating the hologram in 3D dynamic holographic display, and it is a challenge even for the most advanced computer. Many fast algorithms are proposed for speeding the calculation and reducing the memory usage, such as:look-up table (LUT), compressed look-up table (C-LUT), split look-up table (S-LUT), and novel look-up table (N-LUT) based on the point-based method, and full analytical polygon-based methods, one-step polygon-based method based on the polygon-based method. In this presentation, we overview various fast algorithms based on the point-based method and the polygon-based method, and focus on the fast algorithm with low memory usage, the C-LUT, and one-step polygon-based method by the 2D Fourier analysis of the 3D affine transformation. The numerical simulations and the optical experiments are presented, and several other algorithms are compared. The results show that the C-LUT algorithm and the one-step polygon-based method are efficient methods for saving calculation time. It is believed that those methods could be used in the real-time 3D holographic display in future.

  20. Fast-forward Langevin dynamics with momentum flips

    Hijazi, Mahdi; Wilkins, David M.; Ceriotti, Michele

    2018-05-01

    Stochastic thermostats based on the Langevin equation, in which a system is coupled to an external heat bath, are popular methods for temperature control in molecular dynamics simulations due to their ergodicity and their ease of implementation. Traditionally, these thermostats suffer from sluggish behavior in the limit of high friction, unlike thermostats of the Nosé-Hoover family whose performance degrades more gently in the strong coupling regime. We propose a simple and easy-to-implement modification to the integration scheme of the Langevin algorithm that addresses the fundamental source of the overdamped behavior of high-friction Langevin dynamics: if the action of the thermostat causes the momentum of a particle to change direction, it is flipped back. This fast-forward Langevin equation preserves the momentum distribution and so guarantees the correct equilibrium sampling. It mimics the quadratic behavior of Nosé-Hoover thermostats and displays similarly good performance in the strong coupling limit. We test the efficiency of this scheme by applying it to a 1-dimensional harmonic oscillator, as well as to water and Lennard-Jones polymers. The sampling efficiency of the fast-forward Langevin equation thermostat, measured by the correlation time of relevant system variables, is at least as good as the traditional Langevin thermostat, and in the overdamped regime, the fast-forward thermostat performs much better, improving the efficiency by an order of magnitude at the highest frictions we considered.

  1. Accelerated dynamic EPR imaging using fast acquisition and compressive recovery.

    Ahmad, Rizwan; Samouilov, Alexandre; Zweier, Jay L

    2016-12-01

    Electron paramagnetic resonance (EPR) allows quantitative imaging of tissue redox status, which provides important information about ischemic syndromes, cancer and other pathologies. For continuous wave EPR imaging, however, poor signal-to-noise ratio and low acquisition efficiency limit its ability to image dynamic processes in vivo including tissue redox, where conditions can change rapidly. Here, we present a data acquisition and processing framework that couples fast acquisition with compressive sensing-inspired image recovery to enable EPR-based redox imaging with high spatial and temporal resolutions. The fast acquisition (FA) allows collecting more, albeit noisier, projections in a given scan time. The composite regularization based processing method, called spatio-temporal adaptive recovery (STAR), not only exploits sparsity in multiple representations of the spatio-temporal image but also adaptively adjusts the regularization strength for each representation based on its inherent level of the sparsity. As a result, STAR adjusts to the disparity in the level of sparsity across multiple representations, without introducing any tuning parameter. Our simulation and phantom imaging studies indicate that a combination of fast acquisition and STAR (FASTAR) enables high-fidelity recovery of volumetric image series, with each volumetric image employing less than 10 s of scan. In addition to image fidelity, the time constants derived from FASTAR also match closely to the ground truth even when a small number of projections are used for recovery. This development will enhance the capability of EPR to study fast dynamic processes that cannot be investigated using existing EPR imaging techniques. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Distributed solar radiation fast dynamic measurement for PV cells

    Wan, Xuefen; Yang, Yi; Cui, Jian; Du, Xingjing; Zheng, Tao; Sardar, Muhammad Sohail

    2017-10-01

    To study the operating characteristics about PV cells, attention must be given to the dynamic behavior of the solar radiation. The dynamic behaviors of annual, monthly, daily and hourly averages of solar radiation have been studied in detail. But faster dynamic behaviors of solar radiation need more researches. The solar radiation random fluctuations in minute-long or second-long range, which lead to alternating radiation and cool down/warm up PV cell frequently, decrease conversion efficiency. Fast dynamic processes of solar radiation are mainly relevant to stochastic moving of clouds. Even in clear sky condition, the solar irradiations show a certain degree of fast variation. To evaluate operating characteristics of PV cells under fast dynamic irradiation, a solar radiation measuring array (SRMA) based on large active area photodiode, LoRa spread spectrum communication and nanoWatt MCU is proposed. This cross photodiodes structure tracks fast stochastic moving of clouds. To compensate response time of pyranometer and reduce system cost, the terminal nodes with low-cost fast-responded large active area photodiode are placed besides positions of tested PV cells. A central node, consists with pyranometer, large active area photodiode, wind detector and host computer, is placed in the center of the central topologies coordinate to scale temporal envelope of solar irradiation and get calibration information between pyranometer and large active area photodiodes. In our SRMA system, the terminal nodes are designed based on Microchip's nanoWatt XLP PIC16F1947. FDS-100 is adopted for large active area photodiode in terminal nodes and host computer. The output current and voltage of each PV cell are monitored by I/V measurement. AS62-T27/SX1278 LoRa communication modules are used for communicating between terminal nodes and host computer. Because the LoRa LPWAN (Low Power Wide Area Network) specification provides seamless interoperability among Smart Things without the

  3. Dynamically controlled energy dissipation for fast magnetic vortex switching

    Badea, R.; Berezovsky, J.

    2017-09-01

    Manipulation of vortex states in magnetic media provides new routes towards information storage and processing technology. The typical slow relaxation times (˜100 ns) of magnetic vortex dynamics may present an obstacle to the realization of these applications. Here, we investigate how a vortex state in a ferromagnetic microdisk can be manipulated in a way that translates the vortex core while enhancing energy dissipation to rapidly damp the vortex dynamics. We use time-resolved differential magneto-optical Kerr effect microscopy to measure the motion of the vortex core in response to applied magnetic fields. We first map out how the vortex core becomes sequentially trapped by pinning sites as it translates across the disk. After applying a fast magnetic field step to translate the vortex from one pinning site to another, we observe long-lived dynamics of the vortex as it settles to the new equilibrium. We then demonstrate how the addition of a short (<10 ns) magnetic field pulse can induce additional energy dissipation, strongly damping the long-lived dynamics. A model of the vortex dynamics using the Thiele equation of motion explains the mechanism behind this effect.

  4. A Fast Dynamic 64-bit Comparator with Small Transistor Count

    Chua-Chin Wang

    2002-01-01

    Full Text Available In this paper, we propose a 64-bit fast dynamic CMOS comparator with small transistor count. Major features of the proposed comparator are the rearrangement and re-ordering of transistors in the evaluation block of a dynamic cell, and the insertion of a weak n feedback inverter, which helps the pull-down operation to ground. The simulation results given by pre-layout tools, e.g. HSPICE, and post-layout tools, e.g. TimeMill, reveal that the delay is around 2.5 ns while the operating clock rate reaches 100 MHz. A physical chip is fabricated to verify the correctness of our design by using UMC (United Microelectronics Company 0.5 μm (2P2M technology.

  5. Fast growth phenotype of E. coli K-12 from adaptive laboratory evolution does not require intracellular flux rewiring

    Long, Christopher P.; Gonzalez, Jacqueline E.; Feist, Adam M.

    2017-01-01

    and growth condition, to probe the limits of E. coli growth rate and gain insights into fast growth phenotypes. Previous studies have described up to 1.6-fold increases in growth rate following ALE, and have identified key causal genetic mutations and changes in transcriptional patterns. Here, we report...

  6. Intracellular Calcium Dynamics and Autonomic Stimulation in Atrial Fibrillation: Mechanisms and Implications

    Chung-Chuan Chou, MD

    2008-01-01

    Full Text Available While atrial fibrillation is characterized by the co-existence of multiple activation waves within the atria, rapid activations in the pulmonary veins play an important role for the initiation and maintenance of atrial fibrillation. In addition to reentry, non-reentrant mechanisms resulting from abnormal intracellular calcium handling and intracellular calcium overload can also be responsible for these rapid activations in the pulmonary veins. Meanwhile, alterations of autonomic tone, involving both the sympathetic and parasympathetic nervous system, have been implicated in initiating paroxysmal atrial fibrillation. But the effectiveness of autonomic modulation as an adjunctive therapeutic strategy to catheter ablation of atrial fibrillation has been inconsistent. The interactions between the autonomic nervous system and atrial fibrillation are more complex than currently understood and further mechanistic and clinical studies are warranted.

  7. Intracellular localization and dynamics of Hypericin loaded PLLA nanocarriers by image correlation spectroscopy

    Penjweini, Rozhin; Deville, Sarah; D'Olieslaeger, Lien; Berden, Mandy; Ameloot, Marcel; Ethirajan, Anitha

    2015-01-01

    The study of cell-nanoparticle interactions is an important aspect for understanding drug delivery using nanocarriers. In this regard, advances in fluorescence based microscopy are useful for the investigation of temporal and spatial behavior of nanoparticles (NPs) within the intracellular environment. In this work, we focus on the delivery of the naturally-occurring hydrophobic photosensitizer Hypericin in human lung carcinoma A549 cells by using biodegradable poly L-lactic acid NPs. For the...

  8. Cavitation in confined water: ultra-fast bubble dynamics

    Vincent, Olivier; Marmottant, Philippe

    2012-02-01

    In the hydraulic vessels of trees, water can be found at negative pressure. This metastable state, corresponding to mechanical tension, is achieved by evaporation through a porous medium. It can be relaxed by cavitation, i.e. the sudden nucleation of vapor bubbles. Harmful for the tree due to the subsequent emboli of sap vessels, cavitation is on the contrary used by ferns to eject spores very swiftly. We will focus here on the dynamics of the cavitation bubble, which is of primary importance to explain the previously cited natural phenomena. We use the recently developed method of artificial tress, using transparent hydrogels as the porous medium. Our experiments, on water confined in micrometric hydrogel cavities, show an extremely fast dynamics: bubbles are nucleated at the microsecond timescale. For cavities larger than 100 microns, the bubble ``rings'' with damped oscillations at MHz frequencies, whereas for smaller cavities the oscillations become overdamped. This rich dynamics can be accounted for by a model we developed, leading to a modified Rayleigh-Plesset equation. Interestingly, this model predicts the impossibility to nucleate bubbles above a critical confinement that depends on liquid negative pressure and corresponds to approximately 100 nm for 20 MPa tensions.

  9. Differentiation of the intracellular structure of slow- versus fast-twitch muscle fibers through evaluation of the dielectric properties of tissue

    Sanchez, B.; Li, J.; Bragos, R.; Rutkove, S. B.

    2014-05-01

    Slow-twitch (type 1) skeletal muscle fibers have markedly greater mitochondrial content than fast-twitch (type 2) fibers. Accordingly, we sought to determine whether the dielectric properties of these two fiber types differed, consistent with their distinct intracellular morphologies. The longitudinal and transverse dielectric spectrum of the ex vivo rat soleus (a predominantly type 1 muscle) and the superficial layers of rat gastrocnemius (predominantly type 2) (n = 15) were measured in the 1 kHz-10 MHz frequency range and modeled to a resistivity Cole-Cole function. Major differences were especially apparent in the dielectric spectrum in the 1 to 10 MHz range. Specifically, the gastrocnemius demonstrated a well-defined, higher center frequency than the soleus muscle, whereas the soleus muscle showed a greater difference in the modeled zero and infinite resistivities than the gastrocnemius. These findings are consistent with the fact that soleus tissue has larger and more numerous mitochondria than gastrocnemius. Evaluation of tissue at high frequency could provide a novel approach for assessing intracellular structure in health and disease.

  10. Differentiation of the intracellular structure of slow- versus fast-twitch muscle fibers through evaluation of the dielectric properties of tissue

    Sanchez, B; Li, J; Rutkove, S B; Bragos, R

    2014-01-01

    Slow-twitch (type 1) skeletal muscle fibers have markedly greater mitochondrial content than fast-twitch (type 2) fibers. Accordingly, we sought to determine whether the dielectric properties of these two fiber types differed, consistent with their distinct intracellular morphologies. The longitudinal and transverse dielectric spectrum of the ex vivo rat soleus (a predominantly type 1 muscle) and the superficial layers of rat gastrocnemius (predominantly type 2) (n = 15) were measured in the 1 kHz–10 MHz frequency range and modeled to a resistivity Cole–Cole function. Major differences were especially apparent in the dielectric spectrum in the 1 to 10 MHz range. Specifically, the gastrocnemius demonstrated a well-defined, higher center frequency than the soleus muscle, whereas the soleus muscle showed a greater difference in the modeled zero and infinite resistivities than the gastrocnemius. These findings are consistent with the fact that soleus tissue has larger and more numerous mitochondria than gastrocnemius. Evaluation of tissue at high frequency could provide a novel approach for assessing intracellular structure in health and disease. (paper)

  11. Capturing intracellular pH dynamics by coupling its molecular mechanisms within a fully tractable mathematical model.

    Yann Bouret

    Full Text Available We describe the construction of a fully tractable mathematical model for intracellular pH. This work is based on coupling the kinetic equations depicting the molecular mechanisms for pumps, transporters and chemical reactions, which determine this parameter in eukaryotic cells. Thus, our system also calculates the membrane potential and the cytosolic ionic composition. Such a model required the development of a novel algebraic method that couples differential equations for slow relaxation processes to steady-state equations for fast chemical reactions. Compared to classical heuristic approaches based on fitted curves and ad hoc constants, this yields significant improvements. This model is mathematically self-consistent and allows for the first time to establish analytical solutions for steady-state pH and a reduced differential equation for pH regulation. Because of its modular structure, it can integrate any additional mechanism that will directly or indirectly affect pH. In addition, it provides mathematical clarifications for widely observed biological phenomena such as overshooting in regulatory loops. Finally, instead of including a limited set of experimental results to fit our model, we show examples of numerical calculations that are extremely consistent with the wide body of intracellular pH experimental measurements gathered by different groups in many different cellular systems.

  12. Parallel Fast Multipole Boundary Element Method for crustal dynamics

    Quevedo, Leonardo; Morra, Gabriele; Mueller, R Dietmar

    2010-01-01

    Crustal faults and sharp material transitions in the crust are usually represented as triangulated surfaces in structural geological models. The complex range of volumes separating such surfaces is typically three-dimensionally meshed in order to solve equations that describe crustal deformation with the finite-difference (FD) or finite-element (FEM) methods. We show here how the Boundary Element Method, combined with the Multipole approach, can revolutionise the calculation of stress and strain, solving the problem of computational scalability from reservoir to basin scales. The Fast Multipole Boundary Element Method (Fast BEM) tackles the difficulty of handling the intricate volume meshes and high resolution of crustal data that has put classical Finite 3D approaches in a performance crisis. The two main performance enhancements of this method: the reduction of required mesh elements from cubic to quadratic with linear size and linear-logarithmic runtime; achieve a reduction of memory and runtime requirements allowing the treatment of a new scale of geodynamic models. This approach was recently tested and applied in a series of papers by [1, 2, 3] for regional and global geodynamics, using KD trees for fast identification of near and far-field interacting elements, and MPI parallelised code on distributed memory architectures, and is now in active development for crustal dynamics. As the method is based on a free-surface, it allows easy data transfer to geological visualisation tools where only changes in boundaries and material properties are required as input parameters. In addition, easy volume mesh sampling of physical quantities enables direct integration with existing FD/FEM code.

  13. The Slow Dynamics of Intracellular Sodium Concentration Increase the Time Window of Neuronal Integration: A Simulation Study

    Asaph Zylbertal

    2017-09-01

    Full Text Available Changes in intracellular Na+ concentration ([Na+]i are rarely taken into account when neuronal activity is examined. As opposed to Ca2+, [Na+]i dynamics are strongly affected by longitudinal diffusion, and therefore they are governed by the morphological structure of the neurons, in addition to the localization of influx and efflux mechanisms. Here, we examined [Na+]i dynamics and their effects on neuronal computation in three multi-compartmental neuronal models, representing three distinct cell types: accessory olfactory bulb (AOB mitral cells, cortical layer V pyramidal cells, and cerebellar Purkinje cells. We added [Na+]i as a state variable to these models, and allowed it to modulate the Na+ Nernst potential, the Na+-K+ pump current, and the Na+-Ca2+ exchanger rate. Our results indicate that in most cases [Na+]i dynamics are significantly slower than [Ca2+]i dynamics, and thus may exert a prolonged influence on neuronal computation in a neuronal type specific manner. We show that [Na+]i dynamics affect neuronal activity via three main processes: reduction of EPSP amplitude in repeatedly active synapses due to reduction of the Na+ Nernst potential; activity-dependent hyperpolarization due to increased activity of the Na+-K+ pump; specific tagging of active synapses by extended Ca2+ elevation, intensified by concurrent back-propagating action potentials or complex spikes. Thus, we conclude that [Na+]i dynamics should be considered whenever synaptic plasticity, extensive synaptic input, or bursting activity are examined.

  14. Fast reactor safety and computational thermo-fluid dynamics approaches

    Ninokata, Hisashi; Shimizu, Takeshi

    1993-01-01

    This article provides a brief description of the safety principle on which liquid metal cooled fast breeder reactors (LMFBRs) is based and the roles of computations in the safety practices. A number of thermohydraulics models have been developed to date that successfully describe several of the important types of fluids and materials motion encountered in the analysis of postulated accidents in LMFBRs. Most of these models use a mixture of implicit and explicit numerical solution techniques in solving a set of conservation equations formulated in Eulerian coordinates, with special techniques included to specific situations. Typical computational thermo-fluid dynamics approaches are discussed in particular areas of analyses of the physical phenomena relevant to the fuel subassembly thermohydraulics design and that involve describing the motion of molten materials in the core over a large scale. (orig.)

  15. Fast stochastic algorithm for simulating evolutionary population dynamics

    Tsimring, Lev; Hasty, Jeff; Mather, William

    2012-02-01

    Evolution and co-evolution of ecological communities are stochastic processes often characterized by vastly different rates of reproduction and mutation and a coexistence of very large and very small sub-populations of co-evolving species. This creates serious difficulties for accurate statistical modeling of evolutionary dynamics. In this talk, we introduce a new exact algorithm for fast fully stochastic simulations of birth/death/mutation processes. It produces a significant speedup compared to the direct stochastic simulation algorithm in a typical case when the total population size is large and the mutation rates are much smaller than birth/death rates. We illustrate the performance of the algorithm on several representative examples: evolution on a smooth fitness landscape, NK model, and stochastic predator-prey system.

  16. Modeling of Dynamic Fluid Forces in Fast Switching Valves

    Roemer, Daniel Beck; Johansen, Per; Pedersen, Henrik Clemmensen

    2015-01-01

    Switching valves experience opposing fluid forces due to movement of the moving member itself, as the surrounding fluid volume must move to accommodate the movement. This movement-induced fluid force may be divided into three main components; the added mass term, the viscous term and the socalled...... history term. For general valve geometries there are no simple solution to either of these terms. During development and design of such switching valves, it is therefore, common practice to use simple models to describe the opposing fluid forces, neglecting all but the viscous term which is determined...... based on shearing areas and venting channels. For fast acting valves the opposing fluid force may retard the valve performance significantly, if appropriate measures are not taken during the valve design. Unsteady Computational Fluid Dynamics (CFD) simulations are available to simulate the total fluid...

  17. Communications overlapping in fast multipole particle dynamics methods

    Kurzak, Jakub; Pettitt, B. Montgomery

    2005-01-01

    In molecular dynamics the fast multipole method (FMM) is an attractive alternative to Ewald summation for calculating electrostatic interactions due to the operation counts. However when applied to small particle systems and taken to many processors it has a high demand for interprocessor communication. In a distributed memory environment this demand severely limits applicability of the FMM to systems with O(10 K atoms). We present an algorithm that allows for fine grained overlap of communication and computation, while not sacrificing synchronization and determinism in the equations of motion. The method avoids contention in the communication subsystem making it feasible to use the FMM for smaller systems on larger numbers of processors. Our algorithm also facilitates application of multiple time stepping techniques within the FMM. We present scaling at a reasonably high level of accuracy compared with optimized Ewald methods

  18. Development and improvement of measuring method for growth rate of intracellular symbiotic acid-fast bacteria using radioisotopes

    Nakata, Noboru; Fukutomi, Yasuo [National Inst. for Leprosy Research, Higashimurayama, Tokyo (Japan)

    1997-02-01

    The aim of this research group was to investigate the factors which might mediate the growth of mycobacterium lepra and relate to its affinity to the nerve tissue. In this year, constructions of a mycobacterium smegmatis mutant having a high transform ability and a shuttle vector between E. coli and acid-fast bacteria was attempted. From the wild type of m. smegmatis, a highly transformable mutant was obtained and the rate of transformation of the mutant was ca. 10{sup 5} times higher than the parent. And two shuttle vectors for E. coli/acid-fast bacteria; pALKMZErO (6.2 kb) and pHSGM59 (5.4 kb) were constructed. Since the former was unstable in M. smegmatis, the latter vector was used for the following experiments. Expression of `cat` gene cloned by pHSGM59 was identified in M. smegmatis. Further, DNA library of M. leprae was prepared by the use of the vector. Approximately, 1 x 10{sup 4} transformed clones were obtained. The analysis of the plasmids recovered from the clones is under way. (M.N.)

  19. Development and improvement of measuring method for growth rate of intracellular symbiotic acid-fast bacteria using radioisotopes

    Nakata, Noboru; Fukutomi, Yasuo

    1997-01-01

    The aim of this research group was to investigate the factors which might mediate the growth of mycobacterium lepra and relate to its affinity to the nerve tissue. In this year, constructions of a mycobacterium smegmatis mutant having a high transform ability and a shuttle vector between E. coli and acid-fast bacteria was attempted. From the wild type of m. smegmatis, a highly transformable mutant was obtained and the rate of transformation of the mutant was ca. 10 5 times higher than the parent. And two shuttle vectors for E. coli/acid-fast bacteria; pALKMZErO (6.2 kb) and pHSGM59 (5.4 kb) were constructed. Since the former was unstable in M. smegmatis, the latter vector was used for the following experiments. Expression of 'cat' gene cloned by pHSGM59 was identified in M. smegmatis. Further, DNA library of M. leprae was prepared by the use of the vector. Approximately, 1 x 10 4 transformed clones were obtained. The analysis of the plasmids recovered from the clones is under way. (M.N.)

  20. Fast regional readout CMOS Image Sensor for dynamic MLC tracking

    Zin, H.; Harris, E.; Osmond, J.; Evans, P.

    2014-03-01

    Advanced radiotherapy techniques such as volumetric modulated arc therapy (VMAT) require verification of the complex beam delivery including tracking of multileaf collimators (MLC) and monitoring the dose rate. This work explores the feasibility of a prototype Complementary metal-oxide semiconductor Image Sensor (CIS) for tracking these complex treatments by utilising fast, region of interest (ROI) read out functionality. An automatic edge tracking algorithm was used to locate the MLC leaves edges moving at various speeds (from a moving triangle field shape) and imaged with various sensor frame rates. The CIS demonstrates successful edge detection of the dynamic MLC motion within accuracy of 1.0 mm. This demonstrates the feasibility of the sensor to verify treatment delivery involving dynamic MLC up to ~400 frames per second (equivalent to the linac pulse rate), which is superior to any current techniques such as using electronic portal imaging devices (EPID). CIS provides the basis to an essential real-time verification tool, useful in accessing accurate delivery of complex high energy radiation to the tumour and ultimately to achieve better cure rates for cancer patients.

  1. Fast regional readout CMOS image sensor for dynamic MLC tracking

    Zin, H; Harris, E; Osmond, J; Evans, P

    2014-01-01

    Advanced radiotherapy techniques such as volumetric modulated arc therapy (VMAT) require verification of the complex beam delivery including tracking of multileaf collimators (MLC) and monitoring the dose rate. This work explores the feasibility of a prototype Complementary metal-oxide semiconductor Image Sensor (CIS) for tracking these complex treatments by utilising fast, region of interest (ROI) read out functionality. An automatic edge tracking algorithm was used to locate the MLC leaves edges moving at various speeds (from a moving triangle field shape) and imaged with various sensor frame rates. The CIS demonstrates successful edge detection of the dynamic MLC motion within accuracy of 1.0 mm. This demonstrates the feasibility of the sensor to verify treatment delivery involving dynamic MLC up to ∼400 frames per second (equivalent to the linac pulse rate), which is superior to any current techniques such as using electronic portal imaging devices (EPID). CIS provides the basis to an essential real-time verification tool, useful in accessing accurate delivery of complex high energy radiation to the tumour and ultimately to achieve better cure rates for cancer patients.

  2. B-Vitamin Competition: Intracellular and Dissolved B-Vitamins Provide Insight into Marine Microbial Community Dynamics

    Suffridge, C.; Gomez-Consarnau, L.; Qu, P.; Tenenbaum, N.; Fu, F.; Hutchins, D. A.; Sanudo-Wilhelmy, S. A.

    2016-02-01

    The availability of B-vitamins has the ability to directly affect the dynamics of the marine microbial community. Here we show, for the first time, the connection between dissolved and intracellular B-vitamins in a marine environmental community. Two incubation experiments were conducted at a long-term study site (SPOT) in the San Pedro Basin off the coast of Los Angeles, CA. Experiments were conducted in oligotrophic, preupwelling conditions. Due to the 2015 El Niño event, the seasonal upwelling at SPOT did not occur, creating unusually nutrient depleted conditions. Vitamins B1, B7, and B12 were added in addition to macronutrients at concentrations similar to typical SPOT upwelling conditions. Intracellular and dissolved B-vitamin analyses were conducted to determine shifts in cellular B-vitamin requirements as a function of growth rate. We observed a significant bacterioplankton and phytoplankton growth responses with the addition of B-vitamins in a manner that appears to match the enzymatic requirements for these compounds (e.g. B1>B7>B12). Intracellular B-vitamin analysis of T0 samples support this observation, as all four forms of B12 were not detectable within cells, yet multiple forms of B1 and B7 were detected at or near levels previously reported. Treatments with B12 and macronutrients were observed to have the greatest growth rates. This finding, in addition to the apparent lack of intracellular B12 in the initial community, appears to indicate that the initial microbial community was limited by B12. The addition of each vitamin caused a distinct shift in the blooming microbial community. Our results demonstrate that B-vitamins strongly influence not only the growth rate, but also the species composition and species succession of the microbial community as a whole. Large-scale changes to upwelling regimes are predicted in the future ocean; our results indicate that B-vitamins will have a substantial role in controlling microbial community dynamics under

  3. Modelling the Dynamics of Intracellular Processes as an Organisation of Multiple Agents

    Bosse, T.; Jonker, C.M.; Treur, J.; Armano, G.; Merelli, E.; Denzinger, J.; Martin, A.; Miles, S.; Tianfield, H.; Unland, R.

    2005-01-01

    This paper explores how the dynamics of complex biological processes can be modeled as an organisation of multiple agents. This modelling perspective identifies organisational structure occurring in complex decentralised processes and handles complexity of the analysis of the dynamics by structuring

  4. Molecular features contributing to virus-independent intracellular localization and dynamic behavior of the herpesvirus transport protein US9.

    Manuela Pedrazzi

    Full Text Available Reaching the right destination is of vital importance for molecules, proteins, organelles, and cargoes. Thus, intracellular traffic is continuously controlled and regulated by several proteins taking part in the process. Viruses exploit this machinery, and viral proteins regulating intracellular transport have been identified as they represent valuable tools to understand and possibly direct molecules targeting and delivery. Deciphering the molecular features of viral proteins contributing to (or determining this dynamic phenotype can eventually lead to a virus-independent approach to control cellular transport and delivery. From this virus-independent perspective we looked at US9, a virion component of Herpes Simplex Virus involved in anterograde transport of the virus inside neurons of the infected host. As the natural cargo of US9-related vesicles is the virus (or its parts, defining its autonomous, virus-independent role in vesicles transport represents a prerequisite to make US9 a valuable molecular tool to study and possibly direct cellular transport. To assess the extent of this autonomous role in vesicles transport, we analyzed US9 behavior in the absence of viral infection. Based on our studies, Us9 behavior appears similar in different cell types; however, as expected, the data we obtained in neurons best represent the virus-independent properties of US9. In these primary cells, transfected US9 mostly recapitulates the behavior of US9 expressed from the viral genome. Additionally, ablation of two major phosphorylation sites (i.e. Y32Y33 and S34ES36 have no effect on protein incorporation on vesicles and on its localization on both proximal and distal regions of the cells. These results support the idea that, while US9 post-translational modification may be important to regulate cargo loading and, consequently, virion export and delivery, no additional viral functions are required for US9 role in intracellular transport.

  5. The genome of the obligate intracellular parasite Trachipleistophora hominis: new insights into microsporidian genome dynamics and reductive evolution.

    Eva Heinz

    Full Text Available The dynamics of reductive genome evolution for eukaryotes living inside other eukaryotic cells are poorly understood compared to well-studied model systems involving obligate intracellular bacteria. Here we present 8.5 Mb of sequence from the genome of the microsporidian Trachipleistophora hominis, isolated from an HIV/AIDS patient, which is an outgroup to the smaller compacted-genome species that primarily inform ideas of evolutionary mode for these enormously successful obligate intracellular parasites. Our data provide detailed information on the gene content, genome architecture and intergenic regions of a larger microsporidian genome, while comparative analyses allowed us to infer genomic features and metabolism of the common ancestor of the species investigated. Gene length reduction and massive loss of metabolic capacity in the common ancestor was accompanied by the evolution of novel microsporidian-specific protein families, whose conservation among microsporidians, against a background of reductive evolution, suggests they may have important functions in their parasitic lifestyle. The ancestor had already lost many metabolic pathways but retained glycolysis and the pentose phosphate pathway to provide cytosolic ATP and reduced coenzymes, and it had a minimal mitochondrion (mitosome making Fe-S clusters but not ATP. It possessed bacterial-like nucleotide transport proteins as a key innovation for stealing host-generated ATP, the machinery for RNAi, key elements of the early secretory pathway, canonical eukaryotic as well as microsporidian-specific regulatory elements, a diversity of repetitive and transposable elements, and relatively low average gene density. Microsporidian genome evolution thus appears to have proceeded in at least two major steps: an ancestral remodelling of the proteome upon transition to intracellular parasitism that involved reduction but also selective expansion, followed by a secondary compaction of genome

  6. Dynamics of fast ions during sawtooth oscillations in the TEXTOR tokamak measured by collective Thomson scattering

    Nielsen, Stefan Kragh; Salewski, Mirko; Bindslev, Henrik

    2011-01-01

    Experimental investigations of sawteeth interaction with fast ions measured by collective Thomson scattering on TEXTOR are presented. Time-resolved measurements of localized 1D fast-ion distribution functions allow us to study fast-ion dynamics during several sawtooth cycles. Sawtooth oscillation...

  7. Fast Simulation of Dynamic Ultrasound Images Using the GPU.

    Storve, Sigurd; Torp, Hans

    2017-10-01

    Simulated ultrasound data is a valuable tool for development and validation of quantitative image analysis methods in echocardiography. Unfortunately, simulation time can become prohibitive for phantoms consisting of a large number of point scatterers. The COLE algorithm by Gao et al. is a fast convolution-based simulator that trades simulation accuracy for improved speed. We present highly efficient parallelized CPU and GPU implementations of the COLE algorithm with an emphasis on dynamic simulations involving moving point scatterers. We argue that it is crucial to minimize the amount of data transfers from the CPU to achieve good performance on the GPU. We achieve this by storing the complete trajectories of the dynamic point scatterers as spline curves in the GPU memory. This leads to good efficiency when simulating sequences consisting of a large number of frames, such as B-mode and tissue Doppler data for a full cardiac cycle. In addition, we propose a phase-based subsample delay technique that efficiently eliminates flickering artifacts seen in B-mode sequences when COLE is used without enough temporal oversampling. To assess the performance, we used a laptop computer and a desktop computer, each equipped with a multicore Intel CPU and an NVIDIA GPU. Running the simulator on a high-end TITAN X GPU, we observed two orders of magnitude speedup compared to the parallel CPU version, three orders of magnitude speedup compared to simulation times reported by Gao et al. in their paper on COLE, and a speedup of 27000 times compared to the multithreaded version of Field II, using numbers reported in a paper by Jensen. We hope that by releasing the simulator as an open-source project we will encourage its use and further development.

  8. Spatiotemporal intracellular dynamics of neurotrophin and its receptors. Implications for neurotrophin signaling and neuronal function.

    Bronfman, F C; Lazo, O M; Flores, C; Escudero, C A

    2014-01-01

    Neurons possess a polarized morphology specialized to contribute to neuronal networks, and this morphology imposes an important challenge for neuronal signaling and communication. The physiology of the network is regulated by neurotrophic factors that are secreted in an activity-dependent manner modulating neuronal connectivity. Neurotrophins are a well-known family of neurotrophic factors that, together with their cognate receptors, the Trks and the p75 neurotrophin receptor, regulate neuronal plasticity and survival and determine the neuronal phenotype in healthy and regenerating neurons. Is it now becoming clear that neurotrophin signaling and vesicular transport are coordinated to modify neuronal function because disturbances of vesicular transport mechanisms lead to disturbed neurotrophin signaling and to diseases of the nervous system. This chapter summarizes our current understanding of how the regulated secretion of neurotrophin, the distribution of neurotrophin receptors in different locations of neurons, and the intracellular transport of neurotrophin-induced signaling in distal processes are achieved to allow coordinated neurotrophin signaling in the cell body and axons.

  9. Dynamic evolution of Geranium mitochondrial genomes through multiple horizontal and intracellular gene transfers.

    Park, Seongjun; Grewe, Felix; Zhu, Andan; Ruhlman, Tracey A; Sabir, Jamal; Mower, Jeffrey P; Jansen, Robert K

    2015-10-01

    The exchange of genetic material between cellular organelles through intracellular gene transfer (IGT) or between species by horizontal gene transfer (HGT) has played an important role in plant mitochondrial genome evolution. The mitochondrial genomes of Geraniaceae display a number of unusual phenomena including highly accelerated rates of synonymous substitutions, extensive gene loss and reduction in RNA editing. Mitochondrial DNA sequences assembled for 17 species of Geranium revealed substantial reduction in gene and intron content relative to the ancestor of the Geranium lineage. Comparative analyses of nuclear transcriptome data suggest that a number of these sequences have been functionally relocated to the nucleus via IGT. Evidence for rampant HGT was detected in several Geranium species containing foreign organellar DNA from diverse eudicots, including many transfers from parasitic plants. One lineage has experienced multiple, independent HGT episodes, many of which occurred within the past 5.5 Myr. Both duplicative and recapture HGT were documented in Geranium lineages. The mitochondrial genome of Geranium brycei contains at least four independent HGT tracts that are absent in its nearest relative. Furthermore, G. brycei mitochondria carry two copies of the cox1 gene that differ in intron content, providing insight into contrasting hypotheses on cox1 intron evolution. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  10. Analysis methods for fast impurity ion dynamics data

    Den Hartog, D.J.; Almagri, A.F.; Prager, S.C.; Fonck, R.J.

    1994-08-01

    A high resolution spectrometer has been developed and used on the MST reversed-field pinch (RFP) to measure passively impurity ion temperatures and flow velocities with 10 μs temporal resolution. Such measurements of MHD-scale fluctuations are particularly relevant in the RFP because the flow velocity fluctuation induced transport of current (the ''MHD dynamo'') may produce the magnetic field reversal characteristic of an RFP. This instrument will also be used to measure rapid changes in the equilibrium flow velocity, such as occur during locking and H-mode transition. The precision of measurements made to date is <0.6 km/s. The authors are developing accurate analysis techniques appropriate to the reduction of this fast ion dynamics data. Moment analysis and curve-fitting routines have been evaluated for noise sensitivity and robustness. Also presented is an analysis method which correctly separates the flux-surface average of the correlated fluctuations in u and B from the fluctuations due to rigid shifts of the plasma column

  11. Modeling cytoskeletal flow over adhesion sites: competition between stochastic bond dynamics and intracellular relaxation

    Sabass, Benedikt; Schwarz, Ulrich S

    2010-01-01

    In migrating cells, retrograde flow of the actin cytoskeleton is related to traction at adhesion sites located at the base of the lamellipodium. The coupling between the moving cytoskeleton and the stationary adhesions is mediated by the continuous association and dissociation of molecular bonds. We introduce a simple model for the competition between the stochastic dynamics of elastic bonds at the moving interface and relaxation within the moving actin cytoskeleton represented by an internal viscous friction coefficient. Using exact stochastic simulations and an analytical mean field theory, we show that the stochastic bond dynamics lead to biphasic friction laws as observed experimentally. At low internal dissipation, stochastic bond dynamics lead to a regime of irregular stick-and-slip motion. High internal dissipation effectively suppresses cooperative effects among bonds and hence stabilizes the adhesion.

  12. DMPD: Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 16982211 Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. Wullaer...vg) (.html) (.csml) Show Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. PubmedID 1698221...1 Title Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. Author

  13. Dynamics of Intracellular Polymers in Enhanced Biological Phosphorus Removal Processes under Different Organic Carbon Concentrations

    Lizhen Xing

    2013-01-01

    Full Text Available Enhanced biological phosphorus removal (EBPR may deteriorate or fail during low organic carbon loading periods. Polyphosphate accumulating organisms (PAOs in EBPR were acclimated under both high and low organic carbon conditions, and then dynamics of polymers in typical cycles, anaerobic conditions with excess organic carbons, and endogenous respiration conditions were examined. After long-term acclimation, it was found that organic loading rates did not affect the yield of PAOs and the applied low organic carbon concentrations were advantageous for the enrichment of PAOs. A low influent organic carbon concentration induced a high production of extracellular carbohydrate. During both anaerobic and aerobic endogenous respirations, when glycogen decreased to around 80 ± 10 mg C per gram of volatile suspended solids, PAOs began to utilize polyphosphate significantly. Regressed by the first-order reaction model, glycogen possessed the highest degradation rate and then was followed by polyphosphate, while biomass decay had the lowest degradation rate.

  14. Plant dynamics and safety analysis of fast breeder reactors

    Ertel, V.

    1982-01-01

    Some general features of sodium cooled fast breeders which influence the thermohydraulics and differ from LWR'S are discussed. Using the SNR-300 as a reference, some thermohydraulic transients from normal operation and from design accidents are presented. (orig.)

  15. Relaxations and fast dynamics of the plastic crystal cyclo-octanol investigated by broadband dielectric spectroscopy

    Lunkenheimer, Peter

    1997-01-01

    Relaxations and fast dynamics of the plastic crystal cyclo-octanol investigated by broadband dielectric spectroscopy / R. Brand, P. Lunkenheimer, A. Loidl. - In: Physical review. B. 56. 1997. S. R5713-R5716

  16. Dynamic changes of plasma acylcarnitine levels induced by fasting and sunflower oil challenge test in children

    Costa, C. C.; de Almeida, I. T.; Jakobs, C.; Poll-The, B. T.; Duran, M.

    1999-01-01

    The dynamic changes of plasma acylcarnitine levels in 1- to 7-y-old children during fasting and after the ingestion of sunflower oil were studied. Glucose, 3-hydroxybutyrate, acetoacetate, FFA, and individual plasma acylcarnitine levels were monitored in both conditions. Fasting experiments lasted

  17. Suppression of chaos at slow variables by rapidly mixing fast dynamics through linear energy-preserving coupling

    Abramov, Rafail V.

    2011-01-01

    Chaotic multiscale dynamical systems are common in many areas of science, one of the examples being the interaction of the low-frequency dynamics in the atmosphere with the fast turbulent weather dynamics. One of the key questions about chaotic multiscale systems is how the fast dynamics affects chaos at the slow variables, and, therefore, impacts uncertainty and predictability of the slow dynamics. Here we demonstrate that the linear slow-fast coupling with the total energy conservation prop...

  18. The different intracellular action potentials of fast and slow muscle fibres = Différences entre les potentiels d'action intracellulaires de fibres musculaires rapides et lentes

    Wallinga, W.; Gielen, Frans L.H.; Wirtz, Peter; de Jong, Paul; Broenink, Johannes F.

    1985-01-01

    The time course of the intracellular action potential was studied quantitatively, because it is an important factor in the generation of electromyographic signals. In in vivo preparations of the m. EDL and m. soleus of the rat single motor units were stimulated and intracellular action potentials

  19. TRPC1, STIM1, and ORAI influence signal-regulated intracellular and endoplasmic reticulum calcium dynamics in human myometrial cells.

    Murtazina, Dilyara A; Chung, Daesuk; Ulloa, Aida; Bryan, Emily; Galan, Henry L; Sanborn, Barbara M

    2011-08-01

    To explore the relationship between signal-stimulated increases in intracellular calcium ([Ca(2+)](i)) and depletion and refilling of the endoplasmic reticulum (ER) Ca(2+) stores ([Ca(2+)](L)) in human myometrial cells, we measured simultaneous changes in [Ca(2+)](i) and [Ca(2+)](L) using Fura-2 and Mag-fluo-4, respectively, in PHM1-41 immortalized and primary cells derived from pregnant myometrium and in primary cells derived from nonpregnant tissue. Signal- and extracellular Ca(2+)-dependent increases in [Ca(2+)](i) (SRCE) and ER refilling stimulated by oxytocin and cyclopiazonic acid were not inhibited by voltage-operated channel blocker nifedipine or mibefradil, inhibition of Na(+)/Ca(2+) exchange with KB-R7943, or zero extracellular Na(+) in PHM1-41 cells. Gadolinium-inhibited oxytocin- and cyclopiazonic acid-induced SRCE and slowed ER store refilling. TRPC1 mRNA knockdown specifically inhibited oxytocin-stimulated SRCE but had no statistically significant effect on ER store refilling and no effect on either parameter following cyclopiazonic acid treatment. Dominant negative STIMΔERM expression attenuated oxytocin- and thapsigargin-stimulated SRCE. Both STIM1 and ORAI1-ORAI3 mRNA knockdowns significantly attenuated oxytocin- and cyclopiazonic acid-stimulated SRCE. The data also suggest that reduction in STIM1 or ORAI1-ORAI3 mRNA can impede the rate of ER store refilling following removal of SERCA inhibition. These data provide evidence for both distinct and overlapping influences of TRPC1, STIM1, and ORAI1-ORAI3 on SRCE and ER store refilling in human myometrial cells that may contribute to the regulation of myometrial Ca(2+) dynamics. These findings have important implications for understanding the control of myometrial Ca(2+) dynamics in relation to myometrial contractile function.

  20. A predator-2 prey fast-slow dynamical system for rapid predator evolution

    Piltz, Sofia Helena; Veerman, Frits; Maini, Philip K.

    2017-01-01

    We consider adaptive change of diet of a predator population that switches its feeding between two prey populations. We develop a novel 1 fast-3 slow dynamical system to describe the dynamics of the three populations amidst continuous but rapid evolution of the predator's diet choice. The two ext...

  1. Verification and Validation of the New Dynamic Mooring Modules Available in FAST v8

    Wendt, Fabian F.; Andersen, Morten Thøtt; Robertson, Amy N.

    2016-01-01

    The open-source, aero-hydro-servo-elastic wind turbine simulation software FAST v8 (created by the National Renewable Energy Laboratory) was recently coupled to two newly developed mooring dynamics modules: MoorDyn and FEAMooring. MoorDyn is a lumped-mass-based mooring dynamics module developed b...

  2. Longitudinal dynamics of laser-cooled fast ion beams

    Weidemüller, M.; Eike, B.; Eisenbarth, U.

    1999-01-01

    We present recent results of our experiments on laser cooling of fast stored ion beams at the Heidelberg Test Storage Ring. The longitudinal motion of the ions is directly cooled by the light pressure force, whereas efficient transverse cooling is obtained indirectly by longitudinal-transverse co......We present recent results of our experiments on laser cooling of fast stored ion beams at the Heidelberg Test Storage Ring. The longitudinal motion of the ions is directly cooled by the light pressure force, whereas efficient transverse cooling is obtained indirectly by longitudinal....... When applying laser cooling in square-well buckets over long time intervals, hard Coulomb collisions suddenly disappear and the longitudinal temperature drops by about a factor of three. The observed longitudinal behaviour of the beam shows strong resemblance with the transition to an Coulomb...

  3. Fast-forward of quantum adiabatic dynamics in electro-magnetic field

    Masuda, Shumpei; Nakamura, Katsuhiro

    2010-01-01

    We show a method to accelerate quantum adiabatic dynamics of wavefunctions under electro-magnetic field by developing the previous theory (Masuda & Nakamura 2008 and 2010). Firstly we investigate the orbital dynamics of a charged particle. We derive the driving field which accelerates quantum adiabatic dynamics in order to obtain the final adiabatic states except for the spatially uniform phase such as the adiabatic phase in any desired short time. Fast-forward of adiabatic squeezing and tran...

  4. Application of Fast Dynamic Allan Variance for the Characterization of FOGs-Based Measurement While Drilling.

    Wang, Lu; Zhang, Chunxi; Gao, Shuang; Wang, Tao; Lin, Tie; Li, Xianmu

    2016-12-07

    The stability of a fiber optic gyroscope (FOG) in measurement while drilling (MWD) could vary with time because of changing temperature, high vibration, and sudden power failure. The dynamic Allan variance (DAVAR) is a sliding version of the Allan variance. It is a practical tool that could represent the non-stationary behavior of the gyroscope signal. Since the normal DAVAR takes too long to deal with long time series, a fast DAVAR algorithm has been developed to accelerate the computation speed. However, both the normal DAVAR algorithm and the fast algorithm become invalid for discontinuous time series. What is worse, the FOG-based MWD underground often keeps working for several days; the gyro data collected aboveground is not only very time-consuming, but also sometimes discontinuous in the timeline. In this article, on the basis of the fast algorithm for DAVAR, we make a further advance in the fast algorithm (improved fast DAVAR) to extend the fast DAVAR to discontinuous time series. The improved fast DAVAR and the normal DAVAR are used to responsively characterize two sets of simulation data. The simulation results show that when the length of the time series is short, the improved fast DAVAR saves 78.93% of calculation time. When the length of the time series is long ( 6 × 10 5 samples), the improved fast DAVAR reduces calculation time by 97.09%. Another set of simulation data with missing data is characterized by the improved fast DAVAR. Its simulation results prove that the improved fast DAVAR could successfully deal with discontinuous data. In the end, a vibration experiment with FOGs-based MWD has been implemented to validate the good performance of the improved fast DAVAR. The results of the experience testify that the improved fast DAVAR not only shortens computation time, but could also analyze discontinuous time series.

  5. Application of Fast Dynamic Allan Variance for the Characterization of FOGs-Based Measurement While Drilling

    Lu Wang

    2016-12-01

    Full Text Available The stability of a fiber optic gyroscope (FOG in measurement while drilling (MWD could vary with time because of changing temperature, high vibration, and sudden power failure. The dynamic Allan variance (DAVAR is a sliding version of the Allan variance. It is a practical tool that could represent the non-stationary behavior of the gyroscope signal. Since the normal DAVAR takes too long to deal with long time series, a fast DAVAR algorithm has been developed to accelerate the computation speed. However, both the normal DAVAR algorithm and the fast algorithm become invalid for discontinuous time series. What is worse, the FOG-based MWD underground often keeps working for several days; the gyro data collected aboveground is not only very time-consuming, but also sometimes discontinuous in the timeline. In this article, on the basis of the fast algorithm for DAVAR, we make a further advance in the fast algorithm (improved fast DAVAR to extend the fast DAVAR to discontinuous time series. The improved fast DAVAR and the normal DAVAR are used to responsively characterize two sets of simulation data. The simulation results show that when the length of the time series is short, the improved fast DAVAR saves 78.93% of calculation time. When the length of the time series is long ( 6 × 10 5 samples, the improved fast DAVAR reduces calculation time by 97.09%. Another set of simulation data with missing data is characterized by the improved fast DAVAR. Its simulation results prove that the improved fast DAVAR could successfully deal with discontinuous data. In the end, a vibration experiment with FOGs-based MWD has been implemented to validate the good performance of the improved fast DAVAR. The results of the experience testify that the improved fast DAVAR not only shortens computation time, but could also analyze discontinuous time series.

  6. Efficiency optimization of a fast Poisson solver in beam dynamics simulation

    Zheng, Dawei; Pöplau, Gisela; van Rienen, Ursula

    2016-01-01

    Calculating the solution of Poisson's equation relating to space charge force is still the major time consumption in beam dynamics simulations and calls for further improvement. In this paper, we summarize a classical fast Poisson solver in beam dynamics simulations: the integrated Green's function method. We introduce three optimization steps of the classical Poisson solver routine: using the reduced integrated Green's function instead of the integrated Green's function; using the discrete cosine transform instead of discrete Fourier transform for the Green's function; using a novel fast convolution routine instead of an explicitly zero-padded convolution. The new Poisson solver routine preserves the advantages of fast computation and high accuracy. This provides a fast routine for high performance calculation of the space charge effect in accelerators.

  7. FAST

    Zuidmeer-Jongejan, Laurian; Fernandez-Rivas, Montserrat; Poulsen, Lars K.

    2012-01-01

    ABSTRACT: The FAST project (Food Allergy Specific Immunotherapy) aims at the development of safe and effective treatment of food allergies, targeting prevalent, persistent and severe allergy to fish and peach. Classical allergen-specific immunotherapy (SIT), using subcutaneous injections with aqu...

  8. Exploiting Fast-Variables to Understand Population Dynamics and Evolution

    Constable, George W. A.; McKane, Alan J.

    2017-11-01

    We describe a continuous-time modelling framework for biological population dynamics that accounts for demographic noise. In the spirit of the methodology used by statistical physicists, transitions between the states of the system are caused by individual events while the dynamics are described in terms of the time-evolution of a probability density function. In general, the application of the diffusion approximation still leaves a description that is quite complex. However, in many biological applications one or more of the processes happen slowly relative to the system's other processes, and the dynamics can be approximated as occurring within a slow low-dimensional subspace. We review these time-scale separation arguments and analyse the more simple stochastic dynamics that result in a number of cases. We stress that it is important to retain the demographic noise derived in this way, and emphasise this point by showing that it can alter the direction of selection compared to the prediction made from an analysis of the corresponding deterministic model.

  9. Ohm's law in the fast lane: general relatiivistic charge dynamics

    Meier, D.

    2004-01-01

    Fully relativistic and causal equations for the flow of charge in curved spacetime are derived. It is believed that this is the first set of equations to be published that correctly describes the flow of charge, as well as the evolution of the electromagnetic field, in highly dynamical relativistic environments on timescales much shorter than the collapse time (GM/c3).

  10. Fast engineering optimization: A novel highly effective control parameterization approach for industrial dynamic processes.

    Liu, Ping; Li, Guodong; Liu, Xinggao

    2015-09-01

    Control vector parameterization (CVP) is an important approach of the engineering optimization for the industrial dynamic processes. However, its major defect, the low optimization efficiency caused by calculating the relevant differential equations in the generated nonlinear programming (NLP) problem repeatedly, limits its wide application in the engineering optimization for the industrial dynamic processes. A novel highly effective control parameterization approach, fast-CVP, is first proposed to improve the optimization efficiency for industrial dynamic processes, where the costate gradient formulae is employed and a fast approximate scheme is presented to solve the differential equations in dynamic process simulation. Three well-known engineering optimization benchmark problems of the industrial dynamic processes are demonstrated as illustration. The research results show that the proposed fast approach achieves a fine performance that at least 90% of the computation time can be saved in contrast to the traditional CVP method, which reveals the effectiveness of the proposed fast engineering optimization approach for the industrial dynamic processes. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  11. Fluctuation-Response Relation and modeling in systems with fast and slow dynamics

    G. Lacorata

    2007-10-01

    Full Text Available We show how a general formulation of the Fluctuation-Response Relation is able to describe in detail the connection between response properties to external perturbations and spontaneous fluctuations in systems with fast and slow variables. The method is tested by using the 360-variable Lorenz-96 model, where slow and fast variables are coupled to one another with reciprocal feedback, and a simplified low dimensional system. In the Fluctuation-Response context, the influence of the fast dynamics on the slow dynamics relies in a non trivial behavior of a suitable quadratic response function. This has important consequences for the modeling of the slow dynamics in terms of a Langevin equation: beyond a certain intrinsic time interval even the optimal model can give just statistical prediction.

  12. Fast-ion dynamics in the TEXTOR tokamak measured by collective Thomson scattering

    Bindslev, H.; Nielsen, S.K.; Porte, L.

    2006-01-01

    Here we present the first measurements by collective Thomson scattering of the evolution of fast-ion populations in a magnetically confined fusion plasma. 150 kW and 110 Ghz radiation from a gyrotron were scattered in the TEXTOR tokamak plasma with energetic ions generated by neutral beam injection...... and ion cyclotron resonance heating. The temporal behavior of the spatially resolved fast-ion velocity distribution is inferred from the received scattered radiation. The fast-ion dynamics at sawteeth and the slowdown after switch off of auxiliary heating is resolved in time. The latter is shown...

  13. Suppression of chaos at slow variables by rapidly mixing fast dynamics

    Abramov, R.

    2012-04-01

    One of the key questions about chaotic multiscale systems is how the fast dynamics affects chaos at the slow variables, and, therefore, impacts uncertainty and predictability of the slow dynamics. Here we demonstrate that the linear slow-fast coupling with the total energy conservation property promotes the suppression of chaos at the slow variables through the rapid mixing at the fast variables, both theoretically and through numerical simulations. A suitable mathematical framework is developed, connecting the slow dynamics on the tangent subspaces to the infinite-time linear response of the mean state to a constant external forcing at the fast variables. Additionally, it is shown that the uncoupled dynamics for the slow variables may remain chaotic while the complete multiscale system loses chaos and becomes completely predictable at the slow variables through increasing chaos and turbulence at the fast variables. This result contradicts the common sense intuition, where, naturally, one would think that coupling a slow weakly chaotic system with another much faster and much stronger mixing system would result in general increase of chaos at the slow variables.

  14. Intracellular siRNA delivery dynamics of integrin-targeted, PEGylated chitosan-poly(ethylene imine) hybrid nanoparticles

    Ragelle, Héloïse; Colombo, Stefano; Pourcelle, Vincent

    2015-01-01

    chitosan-poly(ethylene imine) hybrid nanoparticles. The amount of intracellular siRNA delivered by αvβ3-targeted versus non-targeted nanoparticles was quantified in the human non-small cell lung carcinoma cell line H1299 expressing enhanced green fluorescent protein (EGFP) using a stem-loop reverse...... that these nanoparticles might end up in late endosomes or lysosomes without releasing their cargo to the cell cytoplasm. Thus, the silencing efficiency of the chitosan-based nanoparticles is strongly dependent on the uptake and the intracellular trafficking in H1299 EGFP cells, which is critical information towards...

  15. The dynamics of target ionization by fast higly charged projectiles

    Moshammer, R.; Ullrich, J.; Unverzagt, M.; Olsen, R.E.; Doerner, R.; Mergel, V.; Schmidt-Boecking, H.

    1995-12-01

    We report on the first kinematically complete investigation of single target ionization by fast heavy ions, on the measurement of all low energy electrons down to zero emission velocities and on the determination of the projectile energy loss on the level of ΔE p /E p ∼10 -7 . This has been achieved by combining a high-resolution recoil-ion momentum spectrometer with a novel 4π electron analyzer. The complete momentum balance between electron, recoil-ion and projectile for single ionization of helium by 3.6 MeV/u Ni 24+ was explored. Low energy electrons are found to be ejected mainly into the forward direction with a most likely longitudinal energy of only 2 eV. The electron momentum is not balanced, as might be expected, by the projectile momentum but is nearly completely compensated by the recoil ion. Surprisingly, the momenta of the helium-atom ''fragments'', the electron and the He 1+ recoil ion, are considerably larger than the total momentum loss of the projectile: the target atom seems to dissociate in the strong, longranging projectile potential. The collision has to be considered as a real three body interaction. (orig.)

  16. Startle Auditory Stimuli Enhance the Performance of Fast Dynamic Contractions

    Fernandez-Del-Olmo, Miguel; Río-Rodríguez, Dan; Iglesias-Soler, Eliseo; Acero, Rafael M.

    2014-01-01

    Fast reaction times and the ability to develop a high rate of force development (RFD) are crucial for sports performance. However, little is known regarding the relationship between these parameters. The aim of this study was to investigate the effects of auditory stimuli of different intensities on the performance of a concentric bench-press exercise. Concentric bench-presses were performed by thirteen trained subjects in response to three different conditions: a visual stimulus (VS); a visual stimulus accompanied by a non-startle auditory stimulus (AS); and a visual stimulus accompanied by a startle auditory stimulus (SS). Peak RFD, peak velocity, onset movement, movement duration and electromyography from pectoralis and tricep muscles were recorded. The SS condition induced an increase in the RFD and peak velocity and a reduction in the movement onset and duration, in comparison with the VS and AS condition. The onset activation of the pectoralis and tricep muscles was shorter for the SS than for the VS and AS conditions. These findings point out to specific enhancement effects of loud auditory stimulation on the rate of force development. This is of relevance since startle stimuli could be used to explore neural adaptations to resistance training. PMID:24489967

  17. Startle auditory stimuli enhance the performance of fast dynamic contractions.

    Miguel Fernandez-Del-Olmo

    Full Text Available Fast reaction times and the ability to develop a high rate of force development (RFD are crucial for sports performance. However, little is known regarding the relationship between these parameters. The aim of this study was to investigate the effects of auditory stimuli of different intensities on the performance of a concentric bench-press exercise. Concentric bench-presses were performed by thirteen trained subjects in response to three different conditions: a visual stimulus (VS; a visual stimulus accompanied by a non-startle auditory stimulus (AS; and a visual stimulus accompanied by a startle auditory stimulus (SS. Peak RFD, peak velocity, onset movement, movement duration and electromyography from pectoralis and tricep muscles were recorded. The SS condition induced an increase in the RFD and peak velocity and a reduction in the movement onset and duration, in comparison with the VS and AS condition. The onset activation of the pectoralis and tricep muscles was shorter for the SS than for the VS and AS conditions. These findings point out to specific enhancement effects of loud auditory stimulation on the rate of force development. This is of relevance since startle stimuli could be used to explore neural adaptations to resistance training.

  18. Design features affecting dynamic behaviour of fast reactor cores

    Kayser, G.; Gouriou, A.

    1981-06-01

    The study of dynamic response of an LMFBR to normal and accidental transients needs first of all a simulation code taking into account all the important effects. The DYN-1 code aims at this target. It represents with a sufficiently accurate meshing the core in a 20 geometry for the thermal and reactivity effects, while the kinetics of this core are calculated with a point model. The primary pool, secondary loops, steam generator are also represented, as well as the control and protective systems. We give a short description of this code. Simpler codes are sometimes good enough for parametric studies

  19. Fast Distributed Dynamics of Semantic Networks via Social Media

    Facundo Carrillo

    2015-01-01

    Full Text Available We investigate the dynamics of semantic organization using social media, a collective expression of human thought. We propose a novel, time-dependent semantic similarity measure (TSS, based on the social network Twitter. We show that TSS is consistent with static measures of similarity but provides high temporal resolution for the identification of real-world events and induced changes in the distributed structure of semantic relationships across the entire lexicon. Using TSS, we measured the evolution of a concept and its movement along the semantic neighborhood, driven by specific news/events. Finally, we showed that particular events may trigger a temporary reorganization of elements in the semantic network.

  20. MD2036: UFO Dynamics Studies and UFO Fast Detection

    Belanger, Philippe; Valette, Matthieu; Lindstrom, Bjorn Hans Filip; Grob, Laura Katharina; Schmidt, Rudiger; Wollmann, Daniel

    2017-01-01

    UFOs are one of the remaining unknown related to LHC operation. Therefore, improving the understanding of UFO dynamics and validating the developed models against direct beam measurements is of fundamental importance in view of LHC operation at 7 TeV and with HL-LHC beam intensities. If not understood, UFOs could also be a showstopper for future machines such as FCC. This MD demonstrates new methods to study the dynamic behaviour of a calibrated UFO, simulated by the interaction of wire scanners with the beam. The events created during the MD were monitored using diamond BLMs in IR7, providing bunch-by-bunch resolution measurements. The analysis presented herein shows that blown-up bunches can be used to identify the plane of movement of UFOs, that bunch profiles and bunch sizes can be measured with dBLMs with good precision, that simulation of expected losses are in good agreement with measurements for oscillating bunches and that the space resolution of the acquisition system used during the MD is about 10 ...

  1. Revealing Hidden Structural Order Controlling Both Fast and Slow Glassy Dynamics in Supercooled Liquids

    Hua Tong

    2018-03-01

    Full Text Available The dynamics of a supercooled liquid near the glass transition is characterized by two-step relaxation, fast β and slow α relaxations. Because of the apparently disordered nature of glassy structures, there have been long debates over whether the origin of drastic slowing-down of the α relaxation accompanied by heterogeneous dynamics is thermodynamic or dynamic. Furthermore, it has been elusive whether there is any deep connection between fast β and slow α modes. To settle these issues, here we introduce a set of new structural order parameters characterizing sterically favored structures with high local packing capability, and then access structure-dynamics correlation by a novel nonlocal approach. We find that the particle mobility is under control of the static order parameter field. The fast β process is controlled by the instantaneous order parameter field locally, resulting in short-time particle-scale dynamics. Then the mobility field progressively develops with time t, following the initial order parameter field from disorder to more ordered regions. As is well known, the heterogeneity in the mobility field (dynamic heterogeneity is maximized with a characteristic length ξ_{4}, when t reaches the relaxation time τ_{α}. We discover that this mobility pattern can be predicted solely by a spatial coarse graining of the initial order parameter field at t=0 over a length ξ without any dynamical information. Furthermore, we find a relation ξ∼ξ_{4}, indicating that the static length ξ grows coherently with the dynamic one ξ_{4} upon cooling. This further suggests an intrinsic link between τ_{α} and ξ: the growth of the static length ξ is the origin of dynamical slowing-down. These we confirm for the first time in binary glass formers both in two and three spatial dimensions. Thus, a static structure has two intrinsic characteristic lengths, particle size and ξ, which control dynamics in local and nonlocal manners, resulting

  2. Revealing Hidden Structural Order Controlling Both Fast and Slow Glassy Dynamics in Supercooled Liquids

    Tong, Hua; Tanaka, Hajime

    2018-01-01

    The dynamics of a supercooled liquid near the glass transition is characterized by two-step relaxation, fast β and slow α relaxations. Because of the apparently disordered nature of glassy structures, there have been long debates over whether the origin of drastic slowing-down of the α relaxation accompanied by heterogeneous dynamics is thermodynamic or dynamic. Furthermore, it has been elusive whether there is any deep connection between fast β and slow α modes. To settle these issues, here we introduce a set of new structural order parameters characterizing sterically favored structures with high local packing capability, and then access structure-dynamics correlation by a novel nonlocal approach. We find that the particle mobility is under control of the static order parameter field. The fast β process is controlled by the instantaneous order parameter field locally, resulting in short-time particle-scale dynamics. Then the mobility field progressively develops with time t , following the initial order parameter field from disorder to more ordered regions. As is well known, the heterogeneity in the mobility field (dynamic heterogeneity) is maximized with a characteristic length ξ4, when t reaches the relaxation time τα. We discover that this mobility pattern can be predicted solely by a spatial coarse graining of the initial order parameter field at t =0 over a length ξ without any dynamical information. Furthermore, we find a relation ξ ˜ξ4, indicating that the static length ξ grows coherently with the dynamic one ξ4 upon cooling. This further suggests an intrinsic link between τα and ξ : the growth of the static length ξ is the origin of dynamical slowing-down. These we confirm for the first time in binary glass formers both in two and three spatial dimensions. Thus, a static structure has two intrinsic characteristic lengths, particle size and ξ , which control dynamics in local and nonlocal manners, resulting in the emergence of the two

  3. Dynamics of the flood response to slow-fast landscape-climate feedbacks

    R. A. P. Perdigão

    2015-06-01

    Full Text Available The dynamical evolution of the flood response to landscape-climate feedbacks is evaluated in a joint nonlinear statistical-dynamical approach. For that purpose, a spatiotemporal sensitivity analysis is conducted on hydrological data from 1976–2008 over 804 catchments throughout Austria, and a general, data-independent nonlinear dynamical model is built linking floods with climate (via precipitation, landscape (via elevation and their feedbacks. These involve nonlinear scale interactions, with landform evolution processes taking place at the millennial scale (slow dynamics, and climate adjusting in years to decades (fast dynamics. The results show that floods are more responsive to spatial (regional than to temporal (decadal variability. Catchments from dry lowlands and high wetlands exhibit similarity between the spatial and temporal sensitivities (spatiotemporal symmetry and low landscape-climate codependence, suggesting they are not coevolving significantly. However, intermediate regions show differences between those sensitivities (symmetry breaks and higher landscape-climate codependence, suggesting undergoing coevolution. The break of symmetry is an emergent behaviour from nonlinear feedbacks within the system. A new coevolution index is introduced relating spatiotemporal symmetry with relative characteristic celerities, which need to be taken into account in hydrological space-time trading. Coevolution is expressed here by the interplay between slow and fast dynamics, represented respectively by spatial and temporal characteristics. The dynamical model captures emerging features of the flood dynamics and nonlinear landscape-climate feedbacks, supporting the nonlinear statistical assessment of spatiotemporally asymmetric flood change. Moreover, it enables the dynamical estimation of flood changes in space and time from the given knowledge at different spatiotemporal conditions. This study ultimately brings to light emerging signatures of

  4. Global fast dynamic terminal sliding mode control for a quadrotor UAV.

    Xiong, Jing-Jing; Zhang, Guo-Bao

    2017-01-01

    A control method based on global fast dynamic terminal sliding mode control (TSMC) technique is proposed to design the flight controller for performing the finite-time position and attitude tracking control of a small quadrotor UAV. Firstly, the dynamic model of the quadrotor is divided into two subsystems, i.e., a fully actuated subsystem and an underactuated subsystem. Secondly, the dynamic flight controllers of the quadrotor are formulated based on global fast dynamic TSMC, which is able to guarantee that the position and velocity tracking errors of all system state variables converge to zero in finite-time. Moreover, the global fast dynamic TSMC is also able to eliminate the chattering phenomenon caused by the switching control action and realize the high precision performance. In addition, the stabilities of two subsystems are demonstrated by Lyapunov theory, respectively. Lastly, the simulation results are given to illustrate the effectiveness and robustness of the proposed control method in the presence of external disturbances. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  5. Measurements of fast ion spatial dynamics during magnetic activity in the RFP

    Goetz, J. A.; Anderson, J. K.; Bonofiglo, P.; Kim, J.; McConnell, R.; Magee, R. M.

    2017-10-01

    Fast ions in the RFP are only weakly affected by a stochastic magnetic field and behave nearly classically in concentration too low to excite Alfvenic activity. At high fast ion concentration sourced by H-NBI in 300kA RFP discharges, a substantial drop in core-localized high pitch fast ions is observed during bursts of coupled EPM and IAE (magnetic island-induced Alfven eigenmode) activity (100-200kHz) through neutral particle analysis. Sourcing instead fast deuterium with NBI, the DD fusion products can measure the dynamics of the fast ion density profile. Both a collimated neutron detector and a new 3MeV fusion proton detector loaned by TriAlpha Energy measure the fast ion density profile with 5cm spatial resolution and 100 μs temporal resolution. In D-NBI, the bursting EPM is excited at slightly lower frequency and the IAE activity is nearly absent, likely due to an isotope effect and loss of wave-particle interaction. In these cases, neutral particle analysis shows little change in the core-localized high pitch fast ion content, and the fusion product profile indicates little change in the fast ion density profile, leaving unexplained the mechanism removing EPM drive. We measure a substantial redistribution of the fast ion profile due to strong lower-frequency ( 30kHz) MHD activity that accompanies the current profile relaxation in the RFP. Profile flattening is strongest in low bulk density discharges, which often occur with a total increase in global neutron flux from acceleration of the beam ions. Work supported by US DoE.

  6. A fast and optimized dynamic economic load dispatch for large scale power systems

    Musse Mohamud Ahmed; Mohd Ruddin Ab Ghani; Ismail Hassan

    2000-01-01

    This paper presents Lagrangian Multipliers (LM) and Linear Programming (LP) based dynamic economic load dispatch (DELD) solution for large-scale power system operations. It is to minimize the operation cost of power generation. units subject to the considered constraints. After individual generator units are economically loaded and periodically dispatched, fast and optimized DELD has been achieved. DELD with period intervals has been taken into consideration The results found from the algorithm based on LM and LP techniques appear to be modest in both optimizing the operation cost and achieving fast computation. (author)

  7. Design factors affecting dynamic behaviour of fast reactor cores. UK review paper

    Brindley, K W [National Nuclear Corporation Ltd., Risley, Warrington (United Kingdom); Perks, M A [United Kingdom Atomic Energy Authority, Risley, Warrington (United Kingdom)

    1982-01-01

    This paper summarises the consideration that has been given in the UK to the following factors that affect the dynamic behaviour of fast reactor cores: fuel design - Pu/u homogeneity, fuel expansion, fuel-clad gaps, uranium fraction. Structural response - CR supports, diagrid, sub-assembly bowing sodium expansion coefficients - low void cores including heterogenous cores. Calculational methods and models are outlined and some experimental results are discussed. (author)

  8. Verification and Validation of the New Dynamic Mooring Modules Available in FAST v8: Preprint

    Wendt, Fabian; Robertson, Amy; Jonkman, Jason; Andersen, Morten T.

    2016-08-01

    The open-source aero-hydro-servo-elastic wind turbine simulation software, FAST v8, was recently coupled to two newly developed mooring dynamics modules: MoorDyn and FEAMooring. MoorDyn is a lumped-mass-based mooring dynamics module developed by the University of Maine, and FEAMooring is a finite-element-based mooring dynamics module developed by Texas A&M University. This paper summarizes the work performed to verify and validate these modules against other mooring models and measured test data to assess their reliability and accuracy. The quality of the fairlead load predictions by the open-source mooring modules MoorDyn and FEAMooring appear to be largely equivalent to what is predicted by the commercial tool OrcaFlex. Both mooring dynamic model predictions agree well with the experimental data, considering the given limitations in the accuracy of the platform hydrodynamic load calculation and the quality of the measurement data.

  9. Intracellular coexpression of CXC- and CC– chemokine receptors and their ligands in human melanoma cell lines and dynamic variations after xenotransplantation

    Pinto, Sandra; Martínez-Romero, Alicia; O’Connor, José-Enrique; Gil-Benso, Rosario; San-Miguel, Teresa; Terrádez, Liria; Monteagudo, Carlos; Callaghan, Robert C

    2014-01-01

    Chemokines have been implicated in tumor progression and metastasis. In melanoma, chemokine receptors have been implicated in organ selective metastasis by regulating processes such as chemoattraction, adhesion and survival. In this study we have analyzed, using flow cytometry, the systems formed by the chemokine receptors CXCR3, CXCR4, CXCR7, CCR7 and CCR10 and their ligands in thirteen human melanoma cell lines (five established from primary tumors and eight established from metastasis from different tissues). WM-115 and WM-266.4 melanoma cell lines (obtained from a primary and a metastatic melanoma respectively) were xenografted in nude mice and the tumors and cell lines derived from them were also analyzed. Our results show that the melanoma cell lines do not express or express in a low degree the chemokine receptors on their cell surface. However, melanoma cell lines show intracellular expression of all the aforementioned receptors and most of their respective ligands. When analyzing the xenografts and the cell lines obtained from them we found variations in the intracellular expression of chemokines and chemokine receptors that differed between the primary and metastatic cell lines. However, as well as in the original cell lines, minute or no expression of the chemokine receptors was observed at the cell surface. Coexpression of chemokine receptors and their ligands was found in human melanoma cell lines. However, this expression is intracellular and receptors are not found at the cell membrane nor chemokines are secreted to the cell medium. The levels of expressed chemokine receptors and their ligands show dynamic variations after xenotransplantation that differ depending on the origin of the cell line (from primary tumor or from metastasis)

  10. In vivo intracellular oxygen dynamics in murine brain glioma and immunotherapeutic response of cytotoxic T cells observed by fluorine-19 magnetic resonance imaging.

    Jia Zhong

    Full Text Available Noninvasive biomarkers of anti-tumoral efficacy are of great importance to the development of therapeutic agents. Tumor oxygenation has been shown to be an important indicator of therapeutic response. We report the use of intracellular labeling of tumor cells with perfluorocarbon (PFC molecules, combined with quantitative ¹⁹F spin-lattice relaxation rate (R₁ measurements, to assay tumor cell oxygen dynamics in situ. In a murine central nervous system (CNS GL261 glioma model, we visualized the impact of Pmel-1 cytotoxic T cell immunotherapy, delivered intravenously, on intracellular tumor oxygen levels. GL261 glioma cells were labeled ex vivo with PFC and inoculated into the mouse striatum. The R₁ of ¹⁹F labeled cells was measured using localized single-voxel magnetic resonance spectroscopy, and the absolute intracellular partial pressure of oxygen (pO₂ was ascertained. Three days after tumor implantation, mice were treated with 2×10⁷ cytotoxic T cells intravenously. At day five, a transient spike in pO₂ was observed indicating an influx of T cells into the CNS and putative tumor cell apoptosis. Immunohistochemistry and quantitative flow cytometry analysis confirmed that the pO₂ was causally related to the T cells infiltration. Surprisingly, the pO₂ spike was detected even though few (∼4×10⁴ T cells actually ingress into the CNS and with minimal tumor shrinkage. These results indicate the high sensitivity of this approach and its utility as a non-invasive surrogate biomarker of anti-cancer immunotherapeutic response in preclinical models.

  11. Intracellular dynamics and fate of polystyrene nanoparticles in A549 Lung epithelial cells monitored by image (cross-) correlation spectroscopy and single particle tracking.

    Deville, Sarah; Penjweini, Rozhin; Smisdom, Nick; Notelaers, Kristof; Nelissen, Inge; Hooyberghs, Jef; Ameloot, Marcel

    2015-10-01

    Novel insights in nanoparticle (NP) uptake routes of cells, their intracellular trafficking and subcellular targeting can be obtained through the investigation of their temporal and spatial behavior. In this work, we present the application of image (cross-) correlation spectroscopy (IC(C)S) and single particle tracking (SPT) to monitor the intracellular dynamics of polystyrene (PS) NPs in the human lung carcinoma A549 cell line. The ensemble kinetic behavior of NPs inside the cell was characterized by temporal and spatiotemporal image correlation spectroscopy (TICS and STICS). Moreover, a more direct interpretation of the diffusion and flow detected in the NP motion was obtained by SPT by monitoring individual NPs. Both techniques demonstrate that the PS NP transport in A549 cells is mainly dependent on microtubule-assisted transport. By applying spatiotemporal image cross-correlation spectroscopy (STICCS), the correlated motions of NPs with the early endosomes, late endosomes and lysosomes are identified. PS NPs were equally distributed among the endolysosomal compartment during the time interval of the experiments. The cotransport of the NPs with the lysosomes is significantly larger compared to the other cell organelles. In the present study we show that the complementarity of ICS-based techniques and SPT enables a consistent elaborate model of the complex behavior of NPs inside biological systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Status review of large fast reactor core designs and their dynamics related features

    Spenke, H.; Kiefhaber, E.

    1982-01-01

    Since several years conventional and unconventional concepts of large fast reactor cores have been investigated in the Federal Republic of Germany at INTERATOM and Kernforschungszentrum Karlsruhe. The work was performed jointly with Belgonucleaire (Belgium). Basically, the studies were aimed at the determination of the performance potential of different core concepts for large fast reactors. Thus the following points were considered: power distribution, neutron fluence and residence time, doubling time, uranium ore consumption, dynamics and safety related features, economics, cooling strategy, core element bowing behaviour. In this paper, the state of the analysis will be presented with emphasis on those points relevant for this meeting. However, we have to make clear, that dynamic and accident studies are still under way and that we are not yet able to cover these aspects in a quantitative manner. This is due to the fact, that the efforts in the DeBeNe-countries have been concentrated on the work necessary for being granted the different licenses for SNR 300, fast breeder prototype reactor near Kalkar. As we expect to obtain these important licenses at the beginning of 1982, an increased man power can be devoted to studies of dynamic and safety problems of large fast cores from that time on. These studies have to fit into the planning recently announced by the utility ESK who will be ordering SNR 2, the first demonstration breeder reactor of Germany, Belgium, Netherlands and France. The planning calls for concept decisions in 1983, leading to an engineering contract for SNR 2 in 1983/1984. Accordingly we shall have to complete and evaluate the ongoing core concept Investigations till 1983 resulting in a subsequent final choice

  13. The dynamic current-voltage characteristic as a powerful tool to analyze fast phenomena in plasma

    Ivan, L. M.; Mihai-Plugaru, M.; Amarandei, G.; Aflori, M.; Dimitriu, D. G.

    2006-01-01

    The static current-voltage characteristic of an electrode immersed in plasma is obtained by slowly increasing and subsequently decreasing the potential on the electrode with respect to the plasma potential or the ground. This characteristic can give us important information about the phenomena that take place in front of the electrode. Current jumps can be evidenced which were often associated with an hysteresis effect, regions with S-type or N-type negative differential resistance, etc. The method is always used when we investigate the appearance of complex space charge configurations (CSCC) in front of an electrode immersed in plasma. However, to investigate the dynamics of such structures or other fast phenomena (like instabilities) which take place in plasma devices with frequencies of tenth, hundred kHz or more, complex investigation techniques must be used. One of the most efficient methods to investigate fast phenomena in plasma devices is the dynamic current-voltage characteristic. This is obtained by recording the time series of the current collected by the electrode when the voltage applied on it is very fast modified (most likely increased) by using a signal generator. In this way, very fast oscillations of the current can be recorded and new phenomena can be evidenced. We used this technique to study the phenomena which take place at the onset of electrostatic instabilities in Q-machine plasma, namely the potential relaxation instability (PRI) and the electrostatic ion-cyclotron instability (EICI). The obtained experimental results prove that the negative differential resistance region in the static current-voltage characteristic is the result of a nonlinear dynamics of a CSCC in form of a double layer (DL) which takes place just before the onset of the instabilities. In the case of the PRI we emphasized current jumps related with the DL appearance, which are not present in the static current-voltage characteristic at high plasma density. (authors)

  14. Coupling fast fluid dynamics and multizone airflow models in Modelica Buildings library to simulate the dynamics of HVAC systems

    Tian, Wei [Univ. of Miami, FL (United States). Dept. of Civil, Architectural and Environmental Engineering; Sevilla, Thomas Alonso [Univ. of Miami, FL (United States). Dept. of Civil, Architectural and Environmental Engineering; Zuo, Wangda [Univ. of Miami, FL (United States). Dept. of Civil, Architectural and Environmental Engineering; Sohn, Michael D. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Energy Analysis and Environmental Impacts Div.

    2017-06-08

    Historically, multizone models are widely used in building airflow and energy performance simulations due to their fast computing speed. However, multizone models assume that the air in a room is well mixed, consequently limiting their application. In specific rooms where this assumption fails, the use of computational fluid dynamics (CFD) models may be an alternative option. Previous research has mainly focused on coupling CFD models and multizone models to study airflow in large spaces. While significant, most of these analyses did not consider the coupled simulation of the building airflow with the building's Heating, Ventilation, and Air-Conditioning (HVAC) systems. This paper tries to fill the gap by integrating the models for HVAC systems with coupled multizone and CFD simulations for airflows, using the Modelica simul ation platform. To improve the computational efficiency, we incorporated a simplified CFD model named fast fluid dynamics (FFD). We first introduce the data synchronization strategy and implementation in Modelica. Then, we verify the implementation using two case studies involving an isothermal and a non-isothermal flow by comparing model simulations to experiment data. Afterward, we study another three cases that are deemed more realistic. This is done by attaching a variable air volume (VAV) terminal box and a VAV system to previous flows to assess the capability of the models in studying the dynamic control of HVAC systems. Finally, we discuss further research needs on the coupled simulation using the models.

  15. Transcription factor assisted loading and enhancer dynamics dictate the hepatic fasting response

    Goldstein, Ido; Baek, Songjoon; Presman, Diego M.; Paakinaho, Ville; Swinstead, Erin E.; Hager, Gordon L.

    2017-01-01

    Fasting elicits transcriptional programs in hepatocytes leading to glucose and ketone production. This transcriptional program is regulated by many transcription factors (TFs). To understand how this complex network regulates the metabolic response to fasting, we aimed at isolating the enhancers and TFs dictating it. Measuring chromatin accessibility revealed that fasting massively reorganizes liver chromatin, exposing numerous fasting-induced enhancers. By utilizing computational methods in combination with dissecting enhancer features and TF cistromes, we implicated four key TFs regulating the fasting response: glucocorticoid receptor (GR), cAMP responsive element binding protein 1 (CREB1), peroxisome proliferator activated receptor alpha (PPARA), and CCAAT/enhancer binding protein beta (CEBPB). These TFs regulate fuel production by two distinctly operating modules, each controlling a separate metabolic pathway. The gluconeogenic module operates through assisted loading, whereby GR doubles the number of sites occupied by CREB1 as well as enhances CREB1 binding intensity and increases accessibility of CREB1 binding sites. Importantly, this GR-assisted CREB1 binding was enhancer-selective and did not affect all CREB1-bound enhancers. Single-molecule tracking revealed that GR increases the number and DNA residence time of a portion of chromatin-bound CREB1 molecules. These events collectively result in rapid synergistic gene expression and higher hepatic glucose production. Conversely, the ketogenic module operates via a GR-induced TF cascade, whereby PPARA levels are increased following GR activation, facilitating gradual enhancer maturation next to PPARA target genes and delayed ketogenic gene expression. Our findings reveal a complex network of enhancers and TFs that dynamically cooperate to restore homeostasis upon fasting. PMID:28031249

  16. Suppression of chaos at slow variables by rapidly mixing fast dynamics through linear energy-preserving coupling

    Abramov, R. V.

    2011-12-01

    Chaotic multiscale dynamical systems are common in many areas of science, one of the examples being the interaction of the low-frequency dynamics in the atmosphere with the fast turbulent weather dynamics. One of the key questions about chaotic multiscale systems is how the fast dynamics affects chaos at the slow variables, and, therefore, impacts uncertainty and predictability of the slow dynamics. Here we demonstrate that the linear slow-fast coupling with the total energy conservation property promotes the suppression of chaos at the slow variables through the rapid mixing at the fast variables, both theoretically and through numerical simulations. A suitable mathematical framework is developed, connecting the slow dynamics on the tangent subspaces to the infinite-time linear response of the mean state to a constant external forcing at the fast variables. Additionally, it is shown that the uncoupled dynamics for the slow variables may remain chaotic while the complete multiscale system loses chaos and becomes completely predictable at the slow variables through increasing chaos and turbulence at the fast variables. This result contradicts the common sense intuition, where, naturally, one would think that coupling a slow weakly chaotic system with another much faster and much stronger chaotic system would result in general increase of chaos at the slow variables.

  17. Conformational landscape of an amyloid intra-cellular domain and Landau-Ginzburg-Wilson paradigm in protein dynamics

    Dai, Jin; He, Jianfeng; Niemi, Antti J.

    2016-01-01

    The Landau-Ginzburg-Wilson paradigm is proposed as a framework, to investigate the conformational landscape of intrinsically unstructured proteins. A universal Cα-trace Landau free energy is deduced from general symmetry considerations, with the ensuing all-atom structure modeled using publicly available reconstruction programs Pulchra and Scwrl. As an example, the conformational stability of an amyloid precursor protein intra-cellular domain (AICD) is inspected; the reference conformation is the crystallographic structure with code 3DXC in Protein Data Bank (PDB) that describes a heterodimer of AICD and a nuclear multi-domain adaptor protein Fe65. Those conformations of AICD that correspond to local or near-local minima of the Landau free energy are identified. For this, the response of the original 3DXC conformation to variations in the ambient temperature is investigated, using the Glauber algorithm. The conclusion is that in isolation the AICD conformation in 3DXC must be unstable. A family of degenerate conformations that minimise the Landau free energy is identified, and it is proposed that the native state of an isolated AICD is a superposition of these conformations. The results are fully in line with the presumed intrinsically unstructured character of isolated AICD and should provide a basis for a systematic analysis of AICD structure in future NMR experiments.

  18. Conformational landscape of an amyloid intra-cellular domain and Landau-Ginzburg-Wilson paradigm in protein dynamics

    Dai, Jin; He, Jianfeng, E-mail: Antti.Niemi@physics.uu.se, E-mail: hjf@bit.edu.cn [School of Physics, Beijing Institute of Technology, Beijing 100081 (China); Niemi, Antti J., E-mail: Antti.Niemi@physics.uu.se, E-mail: hjf@bit.edu.cn [School of Physics, Beijing Institute of Technology, Beijing 100081 (China); Department of Physics and Astronomy, Uppsala University, P.O. Box 803, S-75108 Uppsala (Sweden); Laboratoire de Mathematiques et Physique Theorique CNRS UMR 6083, Fédération Denis Poisson, Université de Tours, Parc de Grandmont, F37200 Tours (France)

    2016-07-28

    The Landau-Ginzburg-Wilson paradigm is proposed as a framework, to investigate the conformational landscape of intrinsically unstructured proteins. A universal Cα-trace Landau free energy is deduced from general symmetry considerations, with the ensuing all-atom structure modeled using publicly available reconstruction programs Pulchra and Scwrl. As an example, the conformational stability of an amyloid precursor protein intra-cellular domain (AICD) is inspected; the reference conformation is the crystallographic structure with code 3DXC in Protein Data Bank (PDB) that describes a heterodimer of AICD and a nuclear multi-domain adaptor protein Fe65. Those conformations of AICD that correspond to local or near-local minima of the Landau free energy are identified. For this, the response of the original 3DXC conformation to variations in the ambient temperature is investigated, using the Glauber algorithm. The conclusion is that in isolation the AICD conformation in 3DXC must be unstable. A family of degenerate conformations that minimise the Landau free energy is identified, and it is proposed that the native state of an isolated AICD is a superposition of these conformations. The results are fully in line with the presumed intrinsically unstructured character of isolated AICD and should provide a basis for a systematic analysis of AICD structure in future NMR experiments.

  19. Platelet activating factor enhances synaptic vesicle exocytosis via PKC, elevated intracellular calcium, and modulation of synapsin 1 dynamics and phosphorylation

    Jennetta W Hammond

    2016-01-01

    Full Text Available Platelet activating factor (PAF is an inflammatory phospholipid signaling molecule implicated in synaptic plasticity, learning and memory and neurotoxicity during neuroinflammation. However, little is known about the intracellular mechanisms mediating PAF’s physiological or pathological effects on synaptic facilitation. We show here that PAF receptors are localized at the synapse. Using fluorescent reporters of presynaptic activity we show that a non-hydrolysable analogue of PAF (cPAF enhances synaptic vesicle release from individual presynaptic boutons by increasing the size or release of the readily releasable pool and the exocytosis rate of the total recycling pool. cPAF also activates previously silent boutons resulting in vesicle release from a larger number of terminals. The underlying mechanism involves elevated calcium within presynaptic boutons and protein kinase C (PKC activation. Furthermore, cPAF increases synapsin I phosphorylation at sites 1 and 3, and increases dispersion of synapsin I from the presynaptic compartment during stimulation, freeing synaptic vesicles for subsequent release. These findings provide a conceptual framework for how PAF, regardless of its cellular origin, can modulate synapses during normal and pathologic synaptic activity.

  20. Dynamics of the single and double ionization of helium in fast proton collisions

    Doerner, R.; Schmidt-Boecking, H.

    1991-08-01

    A new experimental approach, designed to measure differential ionisation and electron capture cross sections for relativistic heavy ion beams, has been developed and was used to investigate dynamic mechanisms of Helium single and double ionisation in collisions with fast protons. Detailed insight into the dynamics of the ionisation process has been obtained. The experimental results prove, that the many-body momentum exchange between all particles involved, the projectile and target nucleus as well as the emitted electrons, has to be incorporated in order to correctly describe the ionisation collision dynamics. For the proton on Helium collision system the transverse momenta of projectile and recoil-ion were found to be of comparable magnitude only for very close collisions and large scattering angles above 1 mrad, which contribute less than 3% to the total ionisation cross section. (orig./HSI) [de

  1. Dynamic analysis of fast-acting solenoid valves using finite element method

    Kwon, Ki Tae; Han, Hwa Taik

    2001-01-01

    It is intended to develop an algorithm for dynamic simulation of fast-acting solenoid valves. The coupled equations of the electric, magnetic, and mechanical systems should be solved simultaneously in a transient nonlinear manner. The transient nonlinear electromagnetic field is analyzed by the Finite Element Method (FEM), which is coupled with nonlinear electronic circuitry. The dynamic movement of the solenoid valve is analyzed at every time step from the force balances acting on the plunger, which include the electromagnetic force calculated from the finite element analysis as well as the elastic force by a spring and the hydrodynamic pressure force along the flow passage. Dynamic responses of the solenoid valves predicted by this algorithm agree well the experimental results including bouncing effects

  2. Fast and robust wavelet-based dynamic range compression and contrast enhancement model with color restoration

    Unaldi, Numan; Asari, Vijayan K.; Rahman, Zia-ur

    2009-05-01

    Recently we proposed a wavelet-based dynamic range compression algorithm to improve the visual quality of digital images captured from high dynamic range scenes with non-uniform lighting conditions. The fast image enhancement algorithm that provides dynamic range compression, while preserving the local contrast and tonal rendition, is also a good candidate for real time video processing applications. Although the colors of the enhanced images produced by the proposed algorithm are consistent with the colors of the original image, the proposed algorithm fails to produce color constant results for some "pathological" scenes that have very strong spectral characteristics in a single band. The linear color restoration process is the main reason for this drawback. Hence, a different approach is required for the final color restoration process. In this paper the latest version of the proposed algorithm, which deals with this issue is presented. The results obtained by applying the algorithm to numerous natural images show strong robustness and high image quality.

  3. Effect of core burnup on the dynamic behavior of fast reactors

    Ilberg, D.; Saphier, D.; Yiftah, S.

    1977-01-01

    Performance of a dynamic analysis, taking burnup changes into account, requires fission-product nuclear data of relatively small uncertainty, suitable burnup calculation models, and dynamic computer programs. These were prepared and used with the following results: (1) Significant changes in static and dynamic parameters were observed when investigating the effect of burnup. These changes were found to be larger than differences introduced by the uncertainty of the fission-product nuclear data. (2) A one-dimensional burnup computer program was prepared. It was found that a burnup model based on the generalized radioactive decay scheme is suitable for accurate fast reactor calculations. (3) Space-time dynamic calculations of fast reactors having different burnup levels were performed. The stability difference between ''clean'' and high burnup cores is greater when local rather than uniform perturbations are inserted along the entire core length. The magnitude by which the ''end-of-life'' core increases the transient excursion over that of the clean core depends on the particular region in which the perturbation is inserted. The end-of-life core will magnify the transient excursion more than the clean core whenever the perturbation is inserted into a region having a higher adjoint flux level than that of the clean core. However, when a reactor safety system operates successfully, the difference in the temperature transient of the clean and end-of-life cores will be relatively small. It is suggested that only the analysis of large local perturbations be performed for end-of-life cores as well as for clean cores in the safety evaluation of fast reactors

  4. Detection of fast oscillating magnetic fields using dynamic multiple TR imaging and Fourier analysis.

    Ki Hwan Kim

    Full Text Available Neuronal oscillations produce oscillating magnetic fields. There have been trials to detect neuronal oscillations using MRI, but the detectability in in vivo is still in debate. Major obstacles to detecting neuronal oscillations are (i weak amplitudes, (ii fast oscillations, which are faster than MRI temporal resolution, and (iii random frequencies and on/off intervals. In this study, we proposed a new approach for direct detection of weak and fast oscillating magnetic fields. The approach consists of (i dynamic acquisitions using multiple times to repeats (TRs and (ii an expanded frequency spectral analysis. Gradient echo echo-planar imaging was used to test the feasibility of the proposed approach with a phantom generating oscillating magnetic fields with various frequencies and amplitudes and random on/off intervals. The results showed that the proposed approach could precisely detect the weak and fast oscillating magnetic fields with random frequencies and on/off intervals. Complex and phase spectra showed reliable signals, while no meaningful signals were observed in magnitude spectra. A two-TR approach provided an absolute frequency spectrum above Nyquist sampling frequency pixel by pixel with no a priori target frequency information. The proposed dynamic multiple-TR imaging and Fourier analysis are promising for direct detection of neuronal oscillations and potentially applicable to any pulse sequences.

  5. Molecular packing, hydrogen bonding, and fast dynamics in lysozyme/trehalose/glycerol and trehalose/glycerol glasses at low hydration

    Lerbret, Adrien; Affouard, Frédéric

    2017-01-01

    Water and glycerol are well-known to facilitate the structural relaxation of amorphous protein matrices. However, several studies evidenced that they may also limit fast ($\\sim$ pico-nanosecond, ps-ns) and small-amplitude ($\\sim$ \\AA ) motions of proteins, which govern their stability in freeze-dried sugar mixtures. To determine how they interact with proteins and sugars in glassy matrices and, thereby, modulate their fast dynamics, we performed molecular dynamics (MD) simulations of lysozyme...

  6. Single-cell resolution of intracellular T cell Ca2+ dynamics in response to frequency-based H2O2 stimulation.

    Kniss-James, Ariel S; Rivet, Catherine A; Chingozha, Loice; Lu, Hang; Kemp, Melissa L

    2017-03-01

    Adaptive immune cells, such as T cells, integrate information from their extracellular environment through complex signaling networks with exquisite sensitivity in order to direct decisions on proliferation, apoptosis, and cytokine production. These signaling networks are reliant on the interplay between finely tuned secondary messengers, such as Ca 2+ and H 2 O 2 . Frequency response analysis, originally developed in control engineering, is a tool used for discerning complex networks. This analytical technique has been shown to be useful for understanding biological systems and facilitates identification of the dominant behaviour of the system. We probed intracellular Ca 2+ dynamics in the frequency domain to investigate the complex relationship between two second messenger signaling molecules, H 2 O 2 and Ca 2+ , during T cell activation with single cell resolution. Single-cell analysis provides a unique platform for interrogating and monitoring cellular processes of interest. We utilized a previously developed microfluidic device to monitor individual T cells through time while applying a dynamic input to reveal a natural frequency of the system at approximately 2.78 mHz stimulation. Although our network was much larger with more unknown connections than previous applications, we are able to derive features from our data, observe forced oscillations associated with specific amplitudes and frequencies of stimuli, and arrive at conclusions about potential transfer function fits as well as the underlying population dynamics.

  7. Geosynchronous magnetic field responses to fast solar wind dynamic pressure enhancements: MHD field model

    T. R. Sun

    2012-08-01

    Full Text Available We performed global MHD simulations of the geosynchronous magnetic field in response to fast solar wind dynamic pressure (Pd enhancements. Taking three Pd enhancement events in 2000 as examples, we found that the main features of the total field B and the dominant component Bz can be efficiently predicted by the MHD model. The predicted B and Bz varies with local time, with the highest level near noon and a slightly lower level around mid-night. However, it is more challenging to accurately predict the responses of the smaller component at the geosynchronous orbit (i.e., Bx and By. In contrast, the limitations of T01 model in predicting responses to fast Pd enhancements are presented.

  8. Ultra-fast dynamics in the nonlinear optical response of silver nanoprism ordered arrays.

    Sánchez-Esquivel, Héctor; Raygoza-Sanchez, Karen Y; Rangel-Rojo, Raúl; Kalinic, Boris; Michieli, Niccolò; Cesca, Tiziana; Mattei, Giovanni

    2018-03-15

    In this work we present the study of the ultra-fast dynamics of the nonlinear optical response of a honeycomb array of silver triangular nanoprisms, performed using a femtosecond pulsed laser tuned with the dipolar surface plasmon resonance of the nanoarray. Nonlinear absorption and refraction, and their time-dependence, were explored using the z-scan and time-resolved excite-probe techniques. Nonlinear absorption is shown to change sign with the input irradiance and the behavior was explained on the basis of a three-level model. The response time was determined to be in the picosecond regime. A technique based on a variable frequency chopper was also used in order to discriminate the thermal and electronic contributions to the nonlinearity, which were found to have opposite signs. All these findings propel the investigated nanoprism arrays as good candidates for applications in advanced ultra-fast nonlinear nanophotonic devices.

  9. New version of the reactor dynamics code DYN3D for Sodium cooled Fast Reactor analyses

    Nikitin, Evgeny [Ecole Polytechnique Federale de Lausanne (Switzerland); Helmholtz-Zentrum Dresden-Rossendorf (HZDR) e.V., Dresden (Germany); Fridman, Emil; Bilodid, Yuri; Kliem, Soeren [Helmholtz-Zentrum Dresden-Rossendorf (HZDR) e.V., Dresden (Germany)

    2017-07-15

    The reactor dynamics code DYN3D being developed at the Helmholtz-Zentrum Dresden-Rossendorf is currently under extension for Sodium cooled Fast Reactor analyses. This paper provides an overview on the new version of DYN3D to be used for SFR core calculations. The current article shortly describes the newly implemented thermal mechanical models, which can account for thermal expansion effects of the reactor core. Furthermore, the methodology used in Sodium cooled Fast Reactor analyses to generate homogenized few-group cross sections is summarized. The conducted and planned verification and validation studies are briefly presented. Related publications containing more detailed descriptions are outlined for the completeness of this overview.

  10. The interaction between AMPKβ2 and the PP1-targeting subunit R6 is dynamically regulated by intracellular glycogen content.

    Oligschlaeger, Yvonne; Miglianico, Marie; Dahlmans, Vivian; Rubio-Villena, Carla; Chanda, Dipanjan; Garcia-Gimeno, Maria Adelaida; Coumans, Will A; Liu, Yilin; Voncken, J Willem; Luiken, Joost J F P; Glatz, Jan F C; Sanz, Pascual; Neumann, Dietbert

    2016-04-01

    AMP-activated protein kinase (AMPK) is a metabolic stress-sensing kinase. We previously showed that glucose deprivation induces autophosphorylation of AMPKβ at Thr-148, which prevents the binding of AMPK to glycogen. Furthermore, in MIN6 cells, AMPKβ1 binds to R6 (PPP1R3D), a glycogen-targeting subunit of protein phosphatase type 1 (PP1), thereby regulating the glucose-induced inactivation of AMPK. In the present study, we further investigated the interaction of R6 with AMPKβ and the possible dependency on Thr-148 phosphorylation status. Yeast two-hybrid (Y2H) analyses and co-immunoprecipitation (IP) of the overexpressed proteins in human embryonic kidney (HEK) 293T) cells revealed that both AMPKβ1 and AMPK-β2 wild-type (WT) isoforms bind to R6. The AMPKβ-R6 interaction was stronger with the muscle-specific AMPKβ2-WT and required association with the substrate-binding motif of R6. When HEK293T cells or C2C12 myotubes were cultured in high-glucose medium, AMPKβ2-WT and R6 weakly interacted. In contrast, glycogen depletion significantly enhanced this protein interaction. Mutation of AMPKβ2 Thr-148 prevented the interaction with R6 irrespective of the intracellular glycogen content. Treatment with the AMPK activator oligomycin enhanced the AMPKβ2-R6 interaction in conjunction with increased Thr-148 phosphorylation in cells grown in low-glucose medium. These data are in accordance with R6 binding directly to AMPKβ2 when both proteins detach from the diminishing glycogen particle, which is simultaneous with increased AMPKβ2 Thr-148 autophosphorylation. Such a model points to a possible control of AMPK by PP1-R6 upon glycogen depletion in muscle. © 2016 Authors; published by Portland Press Limited.

  11. Dynamic structural analysis of a fast shutter with a pneumatic actuator

    Nemov, A., E-mail: nemov@compmechlab.com [St. Petersburg State Polytechnical University, Mechanics and Control Processes Department, Computational Mechanichs Laboratory, Polytechnicheskaya, 29, 195251 St. Petersburg (Russian Federation); Panin, A. [Institut fuer Energieforschung – Plasmaphysik, Forschungszentrum Juelich GmbH, Association EURATOM-FZJ, Member of Trilateral Euregio Cluster, 52425 Juelich (Germany); Borovkov, A.; Khovayko, M.; Zhuravskaya, E. [St. Petersburg State Polytechnical University, Mechanics and Control Processes Department, Computational Mechanichs Laboratory, Polytechnicheskaya, 29, 195251 St. Petersburg (Russian Federation); Krasikov, Yu.; Biel, W.; Neubauer, O. [Institut fuer Energieforschung – Plasmaphysik, Forschungszentrum Juelich GmbH, Association EURATOM-FZJ, Member of Trilateral Euregio Cluster, 52425 Juelich (Germany)

    2013-10-15

    Highlights: ► The dynamical simulations of cCXRS shutter with the use of the LS-DYNA explicit solver are presented and discussed. ► The results of the implicit and explicit solvers are compared; their pros and cons are pointed out. ► The simplified LS-DYNA shutter model for parametric studies has been built up and benchmarked against the full model. ► Oscillations of the shutter arms for different actuator flood times were studied. -- Abstract: Fast shutters can play important role for the ITER diagnostics. They protect diagnostic mirrors, especially the first ones closest to the plasma, between measurements, during dwell time and baking. In a nominal mode, as it is assumed, for example, for the ITER upper port plug no. 3 diagnostics, its shutter stays open ∼1 s and closed ∼21 s. The principal idea of the shutter concept is its ability to make fast transitions between the open and closed positions within fractions of second. A pneumatic actuator produces a pressure force to open or close the shutter. Due to the fast transient nature of the shutter operation, complicated by the parts’ impact interaction, the FE codes using the explicit time integration scheme have an advantage over the implicit ones. The shutter operation is modeled using the explicit solver. Since the shutter dynamic behavior strongly depends on the actuator flood time, different time profiles of the actuator pressure rise (drop) has been verified, including a fast transient with duration of ∼0.1 s. The results of the implicit and explicit solvers are compared. Their pros and cons are pointed out. The system damping, estimations of energy loss and ways to specify damping in FE models are discussed in the paper.

  12. Dynamic structural analysis of a fast shutter with a pneumatic actuator

    Nemov, A.; Panin, A.; Borovkov, A.; Khovayko, M.; Zhuravskaya, E.; Krasikov, Yu.; Biel, W.; Neubauer, O.

    2013-01-01

    Highlights: ► The dynamical simulations of cCXRS shutter with the use of the LS-DYNA explicit solver are presented and discussed. ► The results of the implicit and explicit solvers are compared; their pros and cons are pointed out. ► The simplified LS-DYNA shutter model for parametric studies has been built up and benchmarked against the full model. ► Oscillations of the shutter arms for different actuator flood times were studied. -- Abstract: Fast shutters can play important role for the ITER diagnostics. They protect diagnostic mirrors, especially the first ones closest to the plasma, between measurements, during dwell time and baking. In a nominal mode, as it is assumed, for example, for the ITER upper port plug no. 3 diagnostics, its shutter stays open ∼1 s and closed ∼21 s. The principal idea of the shutter concept is its ability to make fast transitions between the open and closed positions within fractions of second. A pneumatic actuator produces a pressure force to open or close the shutter. Due to the fast transient nature of the shutter operation, complicated by the parts’ impact interaction, the FE codes using the explicit time integration scheme have an advantage over the implicit ones. The shutter operation is modeled using the explicit solver. Since the shutter dynamic behavior strongly depends on the actuator flood time, different time profiles of the actuator pressure rise (drop) has been verified, including a fast transient with duration of ∼0.1 s. The results of the implicit and explicit solvers are compared. Their pros and cons are pointed out. The system damping, estimations of energy loss and ways to specify damping in FE models are discussed in the paper

  13. Towards denoising XMCD movies of fast magnetization dynamics using extended Kalman filter.

    Kopp, M; Harmeling, S; Schütz, G; Schölkopf, B; Fähnle, M

    2015-01-01

    The Kalman filter is a well-established approach to get information on the time-dependent state of a system from noisy observations. It was developed in the context of the Apollo project to see the deviation of the true trajectory of a rocket from the desired trajectory. Afterwards it was applied to many different systems with small numbers of components of the respective state vector (typically about 10). In all cases the equation of motion for the state vector was known exactly. The fast dissipative magnetization dynamics is often investigated by x-ray magnetic circular dichroism movies (XMCD movies), which are often very noisy. In this situation the number of components of the state vector is extremely large (about 10(5)), and the equation of motion for the dissipative magnetization dynamics (especially the values of the material parameters of this equation) is not well known. In the present paper it is shown by theoretical considerations that - nevertheless - there is no principle problem for the use of the Kalman filter to denoise XMCD movies of fast dissipative magnetization dynamics. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Numerical methods and parallel algorithms for fast transient strongly coupled fluid-structure dynamics

    Faucher, V.

    2014-01-01

    This HDR is dedicated to the research in the framework of fast transient dynamics for industrial fluid-structure systems carried in the Laboratory of Dynamic Studies from CEA, implementing new numerical methods for the modelling of complex systems and the parallel solution of large coupled problems on supercomputers. One key issue for the proposed approaches is the limitation to its minimum of the number of non-physical parameters, to cope with constraints arising from the area of usage of the concepts: safety for both nuclear applications (CEA, EDF) and aeronautics (ONERA), protection of the citizen (EC/JRC) in particular. Kinematic constraints strongly coupling structures (namely through unilateral contact) or fluid and structures (with both conformant or non-conformant meshes depending on the geometrical situation) are handled through exact methods including Lagrange Multipliers, with consequences on the solution strategy to be dealt with. This latter aspect makes EPX, the simulation code where the methods are integrated, a singular tool in the community of fast transient dynamics software. The document mainly relies on a description of the modelling needs for industrial fast transient scenarios, for nuclear applications in particular, and the proposed solutions built in the framework of the collaboration between CEA, EDF (via the LaMSID laboratory) and the LaMCoS laboratory from INSA Lyon. The main considered examples are the tearing of the fluid-filled tank after impact, the Code Disruptive Accident for a Generation IV reactor or the ruin of reinforced concrete structures under impact. Innovative models and parallel algorithms are thus proposed, allowing to carry out with robustness and performance the corresponding simulations on supercomputers made of interconnected multi-core nodes, with a strict preservation of the quality of the physical solution. This was particularly the main point of the ANR RePDyn project (2010-2013), with CEA as the pilot. (author

  15. Specialists' meeting on design features affecting a dynamic behaviour of fast reactor cores. Summary report

    NONE

    1982-01-01

    The purpose of the meeting was to review and discuss the effects induced by changes in some design characteristics on overall performances and transient behaviour of fast reactor cores. The main topics discussed in the four technical sessions were: National Review Presentations. Identification of the key issues to be considered in the following sessions; Effects of design changes on performance characteristics. Kinetics models and codes; Evaluation and interpretation of reactivity coefficients. Kinetics calculations for restrained and free-standing cores; Comparison of the dynamic behaviour of homogeneous and heterogeneous cores.

  16. Specialists' meeting on design features affecting a dynamic behaviour of fast reactor cores. Summary report

    1982-01-01

    The purpose of the meeting was to review and discuss the effects induced by changes in some design characteristics on overall performances and transient behaviour of fast reactor cores. The main topics discussed in the four technical sessions were: National Review Presentations. Identification of the key issues to be considered in the following sessions; Effects of design changes on performance characteristics. Kinetics models and codes; Evaluation and interpretation of reactivity coefficients. Kinetics calculations for restrained and free-standing cores; Comparison of the dynamic behaviour of homogeneous and heterogeneous cores

  17. Dynamical analysis on carbon transfer in liquid metal cooled fast breeder reactor

    Kataoka, Tadayuki; Matsumoto, Keishi

    1979-01-01

    The dynamical analysis was undertaken on the exchange of carbon taking place between the structural steels and sodium for the case of a bi-metallic secondary system constituted of type 304 stainless and 2 1/4Cr-1Mo steels, representing the secondary system of a liquid sodium cooled fast breeder reactor. The analysis brought to light the effects to be expected on the long terms carbon transfer behavior of: (a) the surface areas of structural steels in contact with flowing sodium, (b) the thickness of the sodium-boundary layer, (c) the initial carbon concentration in the sodium, and (d) the rate of carbon contamination of the sodium. (author)

  18. Fast-ion dynamics in the TEXTOR tokamak measured by collective Thomson scattering

    Bindslev, H; Nielsen, S K; Porte, L; Hoekzema, J A; Korsholm, S B; Meo, F; Michelsen, P K; Michelsen, S; Oosterbeek, J W; Tsakadze, E L; Westerhof, E; Woskov, P

    2007-01-01

    The dynamics of fast ion populations in the TEXTOR tokamak are measured by collective Thomson scattering of millimetre wave radiation generated by a gyrotron operated at 110 GHz and 100-150 kW. Temporal evolution of the energetic ion velocity distribution at switch on of neutral beam injection (NBI) and the slowdown after switch off of NBI are measured. The turn on phase of the NBI has, furthermore, been measured in plasmas with a range of electron densities and temperatures. All of these measurements are shown to be in good agreement with simple Fokker-Planck modelling. Bulk ion rotation velocity is also measured

  19. Plant dynamics analyses of fast reactor concept: RAPID-A without any control rod

    Kambe, Mitsuru

    1996-01-01

    Plant dynamics analyses of a fast reactor concept RAPID-A without any control rod have been demonstrated in case of reactor startup and sudden change of the primary flow rate. RAIP-A concept involves Lithium Expansion Module (LEM) for inherent reactivity feedback, Lithium Injection Module (LIM) for inherent ultimate shutdown and Lithium Release Module (LRM) for automated reactor startup. LEM consists of Quick-LEM and Slow-LEM. Slow-LEM provides with moderate reactivity addition as decreasing temperature. Quick-LEM assures quick negative reactivity feedback as increasing temperature. Plant dynamics analyses revealed that reactor power is nearly proportional to the primary flow rate even if the flow rate increases suddenly. Fully automated reactor startup from the subcritical condition has been attempted by inserting reactivity at a constant rate by LRM. Allowable rate of reactivity addition has been obtained in respect to Quick-LEM reactivity worth. (author)

  20. BRENDA: a dynamic simulator for a sodium-cooled fast reactor power plant

    Hetrick, D.L.; Sowers, G.W.

    1978-06-01

    This report is a users' manual for one version of BRENDA (Breeder Reactor Nuclear Dynamic Analysis), which is a digital program for simulating the dynamic behavior of a sodium-cooled fast reactor power plant. This version, which contains 57 differential equations, represents a simplified model of the Clinch River Breeder Reactor Project (CRBRP). BRENDA is an input deck for DARE P (Differential Analyzer Replacement, Portable), which is a continuous-system simulation language developed at the University of Arizona. This report contains brief descriptions of DARE P and BRENDA, instructions for using BRENDA in conjunction with DARE P, and some sample output. A list of variable names and a listing for BRENDA are included as appendices

  1. Neutron dynamics of fast-spectrum dedicated cores for waste transmutation

    Massara, S.

    2002-04-01

    Among different scenarios achieving minor actinide transmutation, the possibility of double strata scenarios with critical, fast spectrum, dedicated cores must be checked and quantified. In these cores, the waste fraction has to be at the highest level compatible with safety requirements during normal operation and transient conditions. As reactivity coefficients are poor in such critical cores (low delayed neutron fraction and Doppler feed-back, high coolant void coefficient), their dynamic behaviour during transient conditions must be carefully analysed. Three nitride-fuel configurations have been analysed: two liquid metal-cooled (sodium and lead) and a particle-fuel helium-cooled one. A dynamic code, MAT4 DYN, has been developed during the PhD thesis, allowing the study of loss of flow, reactivity insertion and loss of coolant accidents, and taking into account two fuel geometries (cylindrical and spherical) and two thermal-hydraulics models for the coolant (incompressible for liquid metals and compressible for helium). Dynamics calculations have shown that if the fuel nature is appropriately chosen (letting a sufficient margin during transients), this can counterbalance the bad state of reactivity coefficients for liquid metal-cooled cores, thus proving the interest of this kind of concept. On the other side, the gas-cooled core dynamics is very badly affected by the high value of the helium void coefficient (which is a consequence of the choice of a hard spectrum), this effect being amplified by the very low thermal inertia of particle-fuel design. So, a new kind of concept should be considered for a helium-cooled fast-spectrum dedicated core. (authors)

  2. Contrast-enhanced dynamic MR imaging of parasellar tumor using fast spin-echo sequence

    Kusunoki, Katsusuke; Ohue, Shiro; Ichikawa, Haruhisa; Saito, Masahiro; Sadamoto, Kazuhiko; Sakaki, Saburo; Miki, Hitoshi.

    1995-01-01

    We have applied a new dynamic MRI technique that uses a fast spin-echo sequence to parasellar tumors. This sequence has less susceptible effect and better spatial resolution than a gradient echo sequence, providing faster images than a short spin-echo sequence does. Image was obtained in the coronal or sagittal plane using a 1.5T clinical MRI system, and then, dynamic MR images were acquired every 10 to 20 sec after administration of Gd-DTPA (0.1 mmol/kg). The subjects were 12 patients (5 microadenomas, 5 macroadenomas and 2 Rathke's cleft cysts) and 5 normal volunteers. As for volunteers, the cavernous sinus, pituitary stalk and posterior pituitary gland were contrasted on the first image, followed by visualization of the proximal portion adjacent to the junction of the infundibulum and the anterior pituitary gland, and finally by contrasting the distal portion of the anterior pituitary gland. There was a difference with respect to tumor contrast between microadenomas and macroadenomas. In the case of the macroadenomas, the tumor was contrasted at the same time as, or faster than the anterior pituitary gland, while with the microadenomas the tumor was enhanced later than the anterior pituitary gland. No enhancement with contrast medium was seen in Rathke's cleft cysts. In addition, it was possible to differentiate a recurrent tumor from a piece of muscle placed at surgery since the images obtained by the fast spin-echo sequence were clearer than those obtained by gradient echo sequence. (author)

  3. Fast magnetic resonance fingerprinting for dynamic contrast-enhanced studies in mice.

    Gu, Yuning; Wang, Charlie Y; Anderson, Christian E; Liu, Yuchi; Hu, He; Johansen, Mette L; Ma, Dan; Jiang, Yun; Ramos-Estebanez, Ciro; Brady-Kalnay, Susann; Griswold, Mark A; Flask, Chris A; Yu, Xin

    2018-05-09

    The goal of this study was to develop a fast MR fingerprinting (MRF) method for simultaneous T 1 and T 2 mapping in DCE-MRI studies in mice. The MRF sequences based on balanced SSFP and fast imaging with steady-state precession were implemented and evaluated on a 7T preclinical scanner. The readout used a zeroth-moment-compensated variable-density spiral trajectory that fully sampled the entire k-space and the inner 10 × 10 k-space with 48 and 4 interleaves, respectively. In vitro and in vivo studies of mouse brain were performed to evaluate the accuracy of MRF measurements with both fully sampled and undersampled data. The application of MRF to dynamic T 1 and T 2 mapping in DCE-MRI studies were demonstrated in a mouse model of heterotopic glioblastoma using gadolinium-based and dysprosium-based contrast agents. The T 1 and T 2 measurements in phantom showed strong agreement between the MRF and the conventional methods. The MRF with spiral encoding allowed up to 8-fold undersampling without loss of measurement accuracy. This enabled simultaneous T 1 and T 2 mapping with 2-minute temporal resolution in DCE-MRI studies. Magnetic resonance fingerprinting provides the opportunity for dynamic quantification of contrast agent distribution in preclinical tumor models on high-field MRI scanners. © 2018 International Society for Magnetic Resonance in Medicine.

  4. Polysome profiling in liver identifies dynamic regulation of endoplasmic reticulum translatome by obesity and fasting.

    Fu, Suneng; Fan, Jason; Blanco, Joshua; Gimenez-Cassina, Alfredo; Danial, Nika N; Watkins, Steve M; Hotamisligil, Gökhan S

    2012-08-01

    Obesity-associated metabolic complications are generally considered to emerge from abnormalities in carbohydrate and lipid metabolism, whereas the status of protein metabolism is not well studied. Here, we performed comparative polysome and associated transcriptional profiling analyses to study the dynamics and functional implications of endoplasmic reticulum (ER)-associated protein synthesis in the mouse liver under conditions of obesity and nutrient deprivation. We discovered that ER from livers of obese mice exhibits a general reduction in protein synthesis, and comprehensive analysis of polysome-bound transcripts revealed extensive down-regulation of protein synthesis machinery, mitochondrial components, and bile acid metabolism in the obese translatome. Nutrient availability also plays an important but distinct role in remodeling the hepatic ER translatome in lean and obese mice. Fasting in obese mice partially reversed the overall translatomic differences between lean and obese nonfasted controls, whereas fasting of the lean mice mimicked many of the translatomic changes induced by the development of obesity. The strongest examples of such regulations were the reduction in Cyp7b1 and Slco1a1, molecules involved in bile acid metabolism. Exogenous expression of either gene significantly lowered plasma glucose levels, improved hepatic steatosis, but also caused cholestasis, indicating the fine balance bile acids play in regulating metabolism and health. Together, our work defines dynamic regulation of the liver translatome by obesity and nutrient availability, and it identifies a novel role for bile acid metabolism in the pathogenesis of metabolic abnormalities associated with obesity.

  5. Polysome profiling in liver identifies dynamic regulation of endoplasmic reticulum translatome by obesity and fasting.

    Suneng Fu

    2012-08-01

    Full Text Available Obesity-associated metabolic complications are generally considered to emerge from abnormalities in carbohydrate and lipid metabolism, whereas the status of protein metabolism is not well studied. Here, we performed comparative polysome and associated transcriptional profiling analyses to study the dynamics and functional implications of endoplasmic reticulum (ER-associated protein synthesis in the mouse liver under conditions of obesity and nutrient deprivation. We discovered that ER from livers of obese mice exhibits a general reduction in protein synthesis, and comprehensive analysis of polysome-bound transcripts revealed extensive down-regulation of protein synthesis machinery, mitochondrial components, and bile acid metabolism in the obese translatome. Nutrient availability also plays an important but distinct role in remodeling the hepatic ER translatome in lean and obese mice. Fasting in obese mice partially reversed the overall translatomic differences between lean and obese nonfasted controls, whereas fasting of the lean mice mimicked many of the translatomic changes induced by the development of obesity. The strongest examples of such regulations were the reduction in Cyp7b1 and Slco1a1, molecules involved in bile acid metabolism. Exogenous expression of either gene significantly lowered plasma glucose levels, improved hepatic steatosis, but also caused cholestasis, indicating the fine balance bile acids play in regulating metabolism and health. Together, our work defines dynamic regulation of the liver translatome by obesity and nutrient availability, and it identifies a novel role for bile acid metabolism in the pathogenesis of metabolic abnormalities associated with obesity.

  6. Wide and Fast Wavelength-Swept Fiber Laser Based on Dispersion Tuning for Dynamic Sensing

    Shinji Yamashita

    2009-01-01

    Full Text Available We have developed a unique wide and fast wavelength-swept fiber laser for dynamic and accurate fiber sensing. The wavelength tuning is based on the dispersion tuning technique, which simply modulates the loss/gain in the dispersive laser cavity. By using wideband semiconductor optical amplifiers (SOAs, the sweep range could be as wide as ∼180 nm. Since the cavity contains no mechanical components, such as tunable filters, we could achieve very high sweep rate, as high as ∼200 kHz. We have realized the swept lasers at three wavelength bands, 1550 nm, 1300 nm, and 800 nm, using SOAs along with erbium-doped fiber amplifiers (EDFAs, and in two laser configurations, ring and linear ones. We also succeeded in applying the swept laser for a dynamic fiber-Bragg grating (FBG sensor system. In this paper, we review our researches on the wide and fast wavelength-swept fiber lasers.

  7. Fast Dynamic Simulation-Based Small Signal Stability Assessment and Control

    Acharya, Naresh [General Electric Company, Fairfield, CT (United States); Baone, Chaitanya [General Electric Company, Fairfield, CT (United States); Veda, Santosh [General Electric Company, Fairfield, CT (United States); Dai, Jing [General Electric Company, Fairfield, CT (United States); Chaudhuri, Nilanjan [General Electric Company, Fairfield, CT (United States); Leonardi, Bruno [General Electric Company, Fairfield, CT (United States); Sanches-Gasca, Juan [General Electric Company, Fairfield, CT (United States); Diao, Ruisheng [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Wu, Di [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Huang, Zhenyu [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zhang, Yu [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Jin, Shuangshuang [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zheng, Bin [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Chen, Yousu [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2014-12-31

    Power grid planning and operation decisions are made based on simulation of the dynamic behavior of the system. Enabling substantial energy savings while increasing the reliability of the aging North American power grid through improved utilization of existing transmission assets hinges on the adoption of wide-area measurement systems (WAMS) for power system stabilization. However, adoption of WAMS alone will not suffice if the power system is to reach its full entitlement in stability and reliability. It is necessary to enhance predictability with "faster than real-time" dynamic simulations that will enable the dynamic stability margins, proactive real-time control, and improve grid resiliency to fast time-scale phenomena such as cascading network failures. Present-day dynamic simulations are performed only during offline planning studies, considering only worst case conditions such as summer peak, winter peak days, etc. With widespread deployment of renewable generation, controllable loads, energy storage devices and plug-in hybrid electric vehicles expected in the near future and greater integration of cyber infrastructure (communications, computation and control), monitoring and controlling the dynamic performance of the grid in real-time would become increasingly important. The state-of-the-art dynamic simulation tools have limited computational speed and are not suitable for real-time applications, given the large set of contingency conditions to be evaluated. These tools are optimized for best performance of single-processor computers, but the simulation is still several times slower than real-time due to its computational complexity. With recent significant advances in numerical methods and computational hardware, the expectations have been rising towards more efficient and faster techniques to be implemented in power system simulators. This is a natural expectation, given that the core solution algorithms of most commercial simulators were developed

  8. Interaction of fast and slow dynamics in endocrine control systems with an application to β-cell dynamics.

    Wang, Yi-Fang; Khan, Michael; van den Berg, Hugo A

    2012-01-01

    Endocrine dynamics spans a wide range of time scales, from rapid responses to physiological challenges to with slow responses that adapt the system to the demands placed on it. We outline a non-linear averaging procedure to extract the slower dynamics in a way that accounts properly for the non-linear dynamics of the faster time scale and is applicable to a hierarchy of more than two time scales, although we restrict our discussion to two scales for the sake of clarity. The procedure is exact if the slow time scale is infinitely slow (the dimensionless ε-quantity is the period of the fast time scale fluctuation times an upper bound to the slow time scale rate of change). However, even for an imperfect separation of time scales we find that this construction provides an excellent approximation for the slow-time dynamics at considerably reduced computational cost. Besides the computation advantage, the averaged equation provided a qualitative insight into the interaction of the time scales. We demonstrate the procedure and its advantages by applying the theory to the model described by Tolić et al. [I.M. Tolić, E. Mosekilde, J. Sturis, Modeling the insulin-glucose feedback system: the significance of pulsatile insulin secretion, J. Theor. Biol. 207 (2000) 361-375.] for ultradian dynamics of the glucose-insulin homeostasis feedback system, extended to include β-cell dynamics. We find that the dynamics of the β-cell mass are dependent not only on the glycemic load (amount of glucose administered to the system), but also on the way this load is applied (i.e. three meals daily versus constant infusion), effects that are lost in the inappropriate methods used by the earlier authors. Furthermore, we find that the loss of the protection against apoptosis conferred by insulin that occurs at elevated levels of insulin has a functional role in keeping the β-cell mass in check without compromising regulatory function. We also find that replenishment of β-cells from a

  9. Fast "Feast/Famine" Cycles for Studying Microbial Physiology Under Dynamic Conditions: A Case Study with Saccharomyces cerevisiae.

    Suarez-Mendez, Camilo A; Sousa, Andre; Heijnen, Joseph J; Wahl, Aljoscha

    2014-05-15

    Microorganisms are constantly exposed to rapidly changing conditions, under natural as well as industrial production scale environments, especially due to large-scale substrate mixing limitations. In this work, we present an experimental approach based on a dynamic feast/famine regime (400 s) that leads to repetitive cycles with moderate changes in substrate availability in an aerobic glucose cultivation of Saccharomyces cerevisiae. After a few cycles, the feast/famine produced a stable and repetitive pattern with a reproducible metabolic response in time, thus providing a robust platform for studying the microorganism's physiology under dynamic conditions. We found that the biomass yield was slightly reduced (-5%) under the feast/famine regime, while the averaged substrate and oxygen consumption as well as the carbon dioxide production rates were comparable. The dynamic response of the intracellular metabolites showed specific differences in comparison to other dynamic experiments (especially stimulus-response experiments, SRE). Remarkably, the frequently reported ATP paradox observed in single pulse experiments was not present during the repetitive perturbations applied here. We found that intracellular dynamic accumulations led to an uncoupling of the substrate uptake rate (up to 9-fold change at 20 s.) Moreover, the dynamic profiles of the intracellular metabolites obtained with the feast/famine suggest the presence of regulatory mechanisms that resulted in a delayed response. With the feast famine setup many cellular states can be measured at high frequency given the feature of reproducible cycles. The feast/famine regime is thus a versatile platform for systems biology approaches, which can help us to identify and investigate metabolite regulations under realistic conditions (e.g., large-scale bioreactors or natural environments).

  10. Fast “Feast/Famine” Cycles for Studying Microbial Physiology Under Dynamic Conditions: A Case Study with Saccharomyces cerevisiae

    Suarez-Mendez, Camilo A.; Sousa, Andre; Heijnen, Joseph J.; Wahl, Aljoscha

    2014-01-01

    Microorganisms are constantly exposed to rapidly changing conditions, under natural as well as industrial production scale environments, especially due to large-scale substrate mixing limitations. In this work, we present an experimental approach based on a dynamic feast/famine regime (400 s) that leads to repetitive cycles with moderate changes in substrate availability in an aerobic glucose cultivation of Saccharomyces cerevisiae. After a few cycles, the feast/famine produced a stable and repetitive pattern with a reproducible metabolic response in time, thus providing a robust platform for studying the microorganism’s physiology under dynamic conditions. We found that the biomass yield was slightly reduced (−5%) under the feast/famine regime, while the averaged substrate and oxygen consumption as well as the carbon dioxide production rates were comparable. The dynamic response of the intracellular metabolites showed specific differences in comparison to other dynamic experiments (especially stimulus-response experiments, SRE). Remarkably, the frequently reported ATP paradox observed in single pulse experiments was not present during the repetitive perturbations applied here. We found that intracellular dynamic accumulations led to an uncoupling of the substrate uptake rate (up to 9-fold change at 20 s.) Moreover, the dynamic profiles of the intracellular metabolites obtained with the feast/famine suggest the presence of regulatory mechanisms that resulted in a delayed response. With the feast famine setup many cellular states can be measured at high frequency given the feature of reproducible cycles. The feast/famine regime is thus a versatile platform for systems biology approaches, which can help us to identify and investigate metabolite regulations under realistic conditions (e.g., large-scale bioreactors or natural environments). PMID:24957030

  11. Molecular Dynamics of Water in Wood Studied by Fast Field Cycling Nuclear Magnetic Resonance Relaxometry

    Xinyu Li

    2016-01-01

    Full Text Available Water plays a very important role in wood and wood products. The molecular motion of water in wood is susceptible to thermal activation. Thermal energy makes water molecules more active and weakens the force between water and wood; therefore, the water molecules dynamic properties are greatly influenced. Molecular dynamics study is important for wood drying; this paper therefore focuses on water molecular dynamics in wood through fast field cycling nuclear magnetic resonance relaxometry techniques. The results show that the spin-lattice relaxation rate decreases with the Larmor frequency. Nuclear magnetic resonance dispersion profiles at different temperatures could separate the relaxation contribution of water in bigger pores and smaller pores. The T1 distribution from wide to narrow at 10 MHz Larmor frequency reflects the shrinkage of pore size with the higher temperature. The dependence of spin-lattice relaxation rate on correlation time for water molecular motion based on BPP (proposed by Bloembergen, Purcell, and Pound theory shows that water correlation time increases with higher temperature, and its activation energy, calculated using the Arrhenius transformation equation, is 9.06±0.53 kJ/mol.

  12. Coupled slow and fast surface dynamics in an electrocatalytic oscillator: Model and simulations

    Nascimento, Melke A.; Nagao, Raphael; Eiswirth, Markus; Varela, Hamilton

    2014-01-01

    The co-existence of disparate time scales is pervasive in many systems. In particular for surface reactions, it has been shown that the long-term evolution of the core oscillator is decisively influenced by slow surface changes, such as progressing deactivation. Here we present an in-depth numerical investigation of the coupled slow and fast surface dynamics in an electrocatalytic oscillator. The model consists of four nonlinear coupled ordinary differential equations, investigated over a wide parameter range. Besides the conventional bifurcation analysis, the system was studied by means of high-resolution period and Lyapunov diagrams. It was observed that the bifurcation diagram changes considerably as the irreversible surface poisoning evolves, and the oscillatory region shrinks. The qualitative dynamics changes accordingly and the chaotic oscillations are dramatically suppressed. Nevertheless, periodic cascades are preserved in a confined region of the resistance vs. voltage diagram. Numerical results are compared to experiments published earlier and the latter reinterpreted. Finally, the comprehensive description of the time-evolution in the period and Lyapunov diagrams suggests further experimental studies correlating the evolution of the system's dynamics with changes of the catalyst structure

  13. Numerical and on-site experimental dynamic analysis of the Italian PEC fast reactor building

    Castoldi, A.; Muzzi, F.; Orsi, R.; Panzeri, P.; Pezzoli, P.; Ruggeri, G.; Martelli, A.; Masoni, P.; Brancati, V.

    1988-01-01

    On-site dynamic tests and three-dimensional numerical analysis have been performed by ISMES on behalf of ENEA on the building of the Italian PEC fast reactor test facility. These studies aimed at evaluating the safety margins in the PEC reactor seismic analysis and at providing data for the optimization of the PEC seismic monitoring system. The paper describes the on-site dynamic tests carried out using various excitation methods (two eccentric back-rotating-mass mechanical vibrator, blasting in bore-hole and hydraulic actuators at the building foundations). It highlights the purposes of the four tests campaigns performed at various construction stages and reports the main experimental results. In connection with the experimental tests, a detailed 3D finite element model was set up for fixed base analysis; from the results of the 3D model a simplified equivalent model of the structure was then derived for soil-structure interaction analysis. The mathematical model was validated and calibrated by using the results of the experimental dynamic tests. The main numerical results and the comparisons with the experimental data are presented. (author)

  14. Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis

    Wei Wang

    2017-01-01

    Full Text Available Chloride intracellular channel 1 (CLIC1 is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM database using structure-based virtual screening and molecular dynamics (MD simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulation was employed to validate the stability of interactions between each hit and CLIC1 protein from docking simulation, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA analysis was used to refine the virtual hits. Six TCM compounds with top MM-GBSA scores and ideal-binding models were confirmed as the final hits. Our study provides information about the interaction between TCM compounds and CLIC1 protein, which may be helpful for further experimental investigations. In addition, the top 6 natural products structural scaffolds could serve as building blocks in designing drug-like molecules for CLIC1 inhibition.

  15. Quantitative modeling of the dynamics and intracellular trafficking of far-red light-activatable prodrugs: implications in stimuli-responsive drug delivery system.

    Li, Mengjie; Thapa, Pritam; Rajaputra, Pallavi; Bio, Moses; Peer, Cody J; Figg, William D; You, Youngjae; Woo, Sukyung

    2017-12-01

    The combination of photodynamic therapy (PDT) with anti-tumor agents is a complimentary strategy to treat local cancers. We developed a unique photosensitizer (PS)-conjugated paclitaxel (PTX) prodrug in which a PS is excited by near-infrared wavelength light to site-specifically release PTX while generating singlet oxygen (SO) to effectively kill cancer cells with both PTX and SO. The aim of the present study was to identify the determinants influencing the combined efficacy of this light-activatable prodrug, especially the bystander killing effects from released PTX. Using PS-conjugated PTX as a model system, we developed a quantitative mathematical model describing the intracellular trafficking. Dynamics of the prodrug and the model predictions were verified with experimental data using human cancer cells in vitro. The sensitivity analysis suggested that parameters related to extracellular concentration of released PTX, prodrug uptake, target engagement, and target abundance are critical in determining the combined killing efficacy of the prodrug. We found that released PTX cytotoxicity was most sensitive to the retention time of the drug in extracellular space. Modulating drug internalization and conjugating the agents targeted to abundant receptors may provide a new strategy for maximizing the killing capacity of the far-red light-activatable prodrug system. These results provide guidance for the design of the PDT combination study in vivo and have implications for other stimuli-responsive drug delivery systems.

  16. In vivo optical microprobe imaging for intracellular Ca2+ dynamics in response to dopaminergic signaling in deep brain evoked by cocaine

    Luo, Zhongchi; Pan, Yingtian; Du, Congwu

    2012-02-01

    Ca2+ plays a vital role as second messenger in signal transduction and the intracellular Ca2+ ([Ca2+]i) change is an important indicator of neuronal activity in the brain, including both cortical and subcortical brain regions. Due to the highly scattering and absorption of brain tissue, it is challenging to optically access the deep brain regions (e.g., striatum at >3mm under the brain surface) and image [Ca2+]i changes with cellular resolutions. Here, we present two micro-probe approaches (i.e., microlens, and micro-prism) integrated with a fluorescence microscope modified to permit imaging of neuronal [Ca2+]i signaling in the striatum using a calcium indicator Rhod2(AM). While a micro-prism probe provides a larger field of view to image neuronal network from cortex to striatum, a microlens probe enables us to track [Ca2+]i dynamic change in individual neurons within the brain. Both techniques are validated by imaging neuronal [Ca2+]i changes in transgenic mice with dopamine receptors (D1R, D2R) expressing EGFP. Our results show that micro-prism images can map the distribution of D1R- and D2R-expressing neurons in various brain regions and characterize their different mean [Ca2+]i changes induced by an intervention (e.g., cocaine administration, 8mg/kg., i.p). In addition, microlens images can characterize the different [Ca2+]i dynamics of D1 and D2 neurons in response to cocaine, including new mechanisms of these two types of neurons in striatum. These findings highlight the power of the optical micro-probe imaging for dissecting the complex cellular and molecular insights of cocaine in vivo.

  17. Integrating intracellular dynamics using CompuCell3D and Bionetsolver: applications to multiscale modelling of cancer cell growth and invasion.

    Vivi Andasari

    Full Text Available In this paper we present a multiscale, individual-based simulation environment that integrates CompuCell3D for lattice-based modelling on the cellular level and Bionetsolver for intracellular modelling. CompuCell3D or CC3D provides an implementation of the lattice-based Cellular Potts Model or CPM (also known as the Glazier-Graner-Hogeweg or GGH model and a Monte Carlo method based on the metropolis algorithm for system evolution. The integration of CC3D for cellular systems with Bionetsolver for subcellular systems enables us to develop a multiscale mathematical model and to study the evolution of cell behaviour due to the dynamics inside of the cells, capturing aspects of cell behaviour and interaction that is not possible using continuum approaches. We then apply this multiscale modelling technique to a model of cancer growth and invasion, based on a previously published model of Ramis-Conde et al. (2008 where individual cell behaviour is driven by a molecular network describing the dynamics of E-cadherin and β-catenin. In this model, which we refer to as the centre-based model, an alternative individual-based modelling technique was used, namely, a lattice-free approach. In many respects, the GGH or CPM methodology and the approach of the centre-based model have the same overall goal, that is to mimic behaviours and interactions of biological cells. Although the mathematical foundations and computational implementations of the two approaches are very different, the results of the presented simulations are compatible with each other, suggesting that by using individual-based approaches we can formulate a natural way of describing complex multi-cell, multiscale models. The ability to easily reproduce results of one modelling approach using an alternative approach is also essential from a model cross-validation standpoint and also helps to identify any modelling artefacts specific to a given computational approach.

  18. Reduced dynamics in spin-boson models: A method for both slow and fast bath

    Golosov, Andrei A.; Friesner, Richard A.; Pechukas, Philip

    2000-01-01

    We study a model for treating dissipative systems, a one dimensional quantum system coupled to a harmonic bath. The dynamics of such a system can be described by Feynman's path integral expression for the reduced density matrix. In this formulation the interaction of the system with the environment is stored in the influence functional. Recently we showed that fast environmental modes that give rise to correlations in the influence functional which are short range in time can be treated efficiently by a memory equation algorithm, which is a discretized version of a master equation. In this work we extend this approach to treat slow environmental modes as well, thereby efficiently linking adiabatic and nonadiabatic regimes. In this extended method the long range correlations in the influence functional arising from slow bath modes are taken into account through Stock's semiclassical self-consistent-field approach. (c) 2000 American Institute of Physics

  19. A fast and systematic procedure to develop dynamic models of bioprocesses: application to microalgae cultures

    J. Mailier

    2010-09-01

    Full Text Available The purpose of this paper is to report on the development of a procedure for inferring black-box, yet biologically interpretable, dynamic models of bioprocesses based on sets of measurements of a few external components (biomass, substrates, and products of interest. The procedure has three main steps: (a the determination of the number of macroscopic biological reactions linking the measured components; (b the estimation of a first reaction scheme, which has interesting mathematical properties, but might lack a biological interpretation; and (c the "projection" (or transformation of this reaction scheme onto a biologically-consistent scheme. The advantage of the method is that it allows the fast prototyping of models for the culture of microorganisms that are not well documented. The good performance of the third step of the method is demonstrated by application to an example of microalgal culture.

  20. Connection between slow and fast dynamics of molecular liquids around the glass transition

    Niss, Kristine; Dalle-Ferrier, Cecile; Frick, Bernhard; Russo, Daniela; Dyre, Jeppe; Alba-Simionesco, Christiane

    2010-01-01

    The mean-square displacement (MSD) was measured by neutron scattering at various temperatures and pressures for a number of molecular glass-forming liquids. The MSD is invariant along the glass-transition line at the pressure studied, thus establishing an 'intrinsic' Lindemann criterion for any given liquid. A one-to-one connection between the MSD's temperature dependence and the liquid's fragility is found when the MSD is evaluated on a time scale of ∼4 ns, but does not hold when the MSD is evaluated at shorter times. The findings are discussed in terms of the elastic model and the role of relaxations, and the correlations between slow and fast dynamics are addressed.

  1. Dynamic operator actions analysis for inherently safe fast reactors and light water reactors

    Ho, V.; Apostolakis, G.

    1988-01-01

    A comparative dynamic human actions analysis of inherently safe fast reactors (ISFRs) and light water reactors (LWRs) in terms of systems response and estimated human error rates is presented. Brief overviews of the ISFR and LWR systems are given to illustrate the design differences. Key operator actions required by the ISFR reactor shutdown and decay heat removal systems are identified and are compared with those of the LWR. It is observed that, because of the passive nature of the ISFR safety-related systems, a large time window is available for operator actions during transient events. Furthermore, these actions are fewer in number, are less complex, and have lower error rates and less severe consequences than those of the LWRs. We expect the ISFR operator errors' contribution to risk is smaller (at least in the context of the existing human reliability models) than that of the LWRs. (author)

  2. Dynamic analysis of Korean nuclear fuel cycle with fast reactor systems

    Jeong, Chang Joon

    2004-12-01

    The Korean nuclear fuel cycle scenario was analyzed by the dynamic analysis method, including Pressurized Water Reactor (PWR), Canadian Deuterium Uranium (CANDU) and fast reactor systems. For the once-through fuel cycle model, the existing nuclear power plant construction plan was considered up to 2016, while the nuclear demand growth rate from the year 2016 was assumed to be 1%. After setting up the once-through fuel cycle model, the Korea Advanced Liquid Metal Reactor (KALIMER) scenario was modeled to investigate the fuel cycle parameters. For the analysis of the fast reactor fuel cycle, both KAILMER-150 and KALIMER-600 reactors were considered. In this analysis, the spent fuel inventory as well as the amount of plutonium, Minor Actinides (MA) and Fission Products (FP) of the recycling fuel cycle was estimated and compared to that of the once-through fuel cycle. Results of the once-through fuel cycle calculation showed that the demand grows up to 64 GWe and total amount of spent fuel would be ∼102 kt in 2100. If the KALIMER scenario is implemented, the total spent fuel inventory can be reduced by ∼80%. However it was found that the KALIMER scenario does not contribute to reduce the amount of MA and FP, which is important when designing a repository. For the further destruction of MA, an actinide burner can be considered in the future nuclear fuel cycle

  3. Dynamic measurements at THz frequencies with a fast rotary delay line

    Guerboukha, Hichem; Markov, Andrey; Qu, Hang; Skorobogatiy, Maksim

    2016-02-01

    Fabrication, characterization, and applications of a fast rotary linear optical delay line (FRLODL) for THz time-domain spectroscopy are presented. The FRLODL features two reflective surfaces with spatially separated incoming and outgoing beams. It has been manufactured using CNC machining. A linear dependence of the optical delay on the rotation angle allows a straightforward extraction of the conversion factor between the acquisition time (in ms) and the terahertz pulse time (in ps). The FRLODL has been tested using rotation speeds of up to 48 Hz, corresponding to an acquisition rate of up to 192 Hz with four blades incorporated on the same disk. At high speeds we observe a decrease of the bandwidth due to the limitations of the electronics, in particular, the transimpedance amplifier. An error analysis is performed by experimentally evaluating the signal-to-noise ratio and the dynamic range. With regard to the applications of the FRLODL, we first present observation of the evaporation of liquids, namely water, acetone and methanol. We then demonstrate monitoring of the spray painting process. Finally, detection of fast moving objects at 1 m/s and their thickness characterization are presented.

  4. Fast fission phenomenon, deep inelastic reactions and compound nucleus formation described within a dynamical macroscopic model

    Gregoire, C.; Ngo, C.; Remaud, B.

    1982-01-01

    We present a dynamical model to describe dissipative heavy ion reactions. It treats explicitly the relative motion of the two ions, the mass asymmetry of the system and the projection of the isospin of each ion. The deformations, which are induced during the collision, are simulated with a time-dependent interaction potential. This is done by a time-dependent transition between a sudden interaction potential in the entrance channel and an adiabatic potential in the exit channel. The model allows us to compute the compound-nucleus cross section and multidifferential cross-sections for deep inelastic reactions. In addition, for some systems, and under certain conditions which are discussed in detail, a new dissipative heavy ion collision appears: fast-fission phenomenon which has intermediate properties between deep inelastic and compound nucleus reactions. The calculated properties concerning fast fission are compared with experimental results and reproduce some of those which could not be understood as belonging to deep inelastic or compound-nucleus reactions. (orig.)

  5. Dynamic Ureas with Fast and pH-Independent Hydrolytic Kinetics.

    Cai, Kaimin; Ying, Hanze; Cheng, Jianjun

    2018-04-06

    Low cost, high performance hydrolysable polymers are of great importance in biomedical applications and materials industries. While many applications require materials to have a degradation profile insensitive to external pH to achieve consistent release profiles under varying conditions, hydrolysable chemistry techniques developed so far have pH-dependent hydrolytic kinetics. This work reports the design and synthesis of a new type of hydrolysable polymer that has identical hydrolysis kinetics from pH 3 to 11. The unprecedented pH independent hydrolytic kinetics of the aryl ureas were shown to be related to the dynamic bond dissociation controlled hydrolysis mechanism; the resulting hindered poly(aryl urea) can be degraded with a hydrolysis half-life of 10 min in solution. More importantly, these fast degradable hindered aromatic polyureas can be easily prepared by addition polymerization from commercially available monomers and are resistant to hydrolysis in solid form for months under ambient storage conditions. The combined features of good stability in solid state and fast hydrolysis at various pH values is unprecedented in polyurea material, and will have implications for materials design and applications, such as sacrificial coatings and biomaterials. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Forecasting municipal solid waste generation in a fast-growing urban region with system dynamics modeling

    Dyson, Brian; Chang, N.-B.

    2005-01-01

    Both planning and design of municipal solid waste management systems require accurate prediction of solid waste generation. Yet achieving the anticipated prediction accuracy with regard to the generation trends facing many fast-growing regions is quite challenging. The lack of complete historical records of solid waste quantity and quality due to insufficient budget and unavailable management capacity has resulted in a situation that makes the long-term system planning and/or short-term expansion programs intangible. To effectively handle these problems based on limited data samples, a new analytical approach capable of addressing socioeconomic and environmental situations must be developed and applied for fulfilling the prediction analysis of solid waste generation with reasonable accuracy. This study presents a new approach - system dynamics modeling - for the prediction of solid waste generation in a fast-growing urban area based on a set of limited samples. To address the impact on sustainable development city wide, the practical implementation was assessed by a case study in the city of San Antonio, Texas (USA). This area is becoming one of the fastest-growing regions in North America due to the economic impact of the North American Free Trade Agreement (NAFTA). The analysis presents various trends of solid waste generation associated with five different solid waste generation models using a system dynamics simulation tool - Stella[reg]. Research findings clearly indicate that such a new forecasting approach may cover a variety of possible causative models and track inevitable uncertainties down when traditional statistical least-squares regression methods are unable to handle such issues

  7. Theoretical and experimental investigation of the nonlinear structural dynamics of Fast Breeder Reactor fuel elements

    Liebe, R.

    1978-04-01

    This study describes theoretical and experimental investigations of the dynamic deformation behavior of single and clustered fuel elements under local fault conditions in a Fast Breeder Reactor core. In particular an energetic molten-fuel-coolant-interaction (FCI) is assumed in one subassembly with corresponding pressure pulses, which may rupture the wrapper and load the adjacent fuel elements impulsively. Associated coherent structural deformation may exceed tolerable and damage the control rods. To attack the outlined coupled fluid-structure-interaction problem it is assumed, that the loading at the structures is known in space and time, and that there is no feedback from the deformation response. Then current FCI-knowledge and experience from underwater core model explosion tests is utilized to estimate upper limits of relevant pulse characteristics. As a first step the static carrying capacity of the rigid-plastic hexagonal wrapper tube is calculated using the methods of limit analysis. Then for a general dynamic simulation of the complete elastoplastic subassembly response the concept of a discrete nonlinear hinge is introduced. A corresponding physical lumped parameter hinge model is presented, and general equations of motion are derived using D'Alembert's principle. Application to the static and dynamic analysis of a single complete fuel element includes the semiempirical modelling of the fuel-pin bundle by a homogeneous compressible medium. Most important conclusions are concerning the capability of the theoretical models, the failure modes and threshold load levels of single as well as clustered SNR-300 fuel elements and the safety relevant finding, that only limited deformations are found in the first row around the incident element. This shows in agreement with explosion test results that the structured and closely spaced fuel elements constitute an effective, inherent barrier against extreme dynamic loadings. (orig.) [de

  8. Dynamic relations between fast-food restaurant and body weight status: a longitudinal and multilevel analysis of Chinese adults.

    Xu, Hongwei; Short, Susan E; Liu, Tao

    2013-03-01

    Mixed findings have been reported on the association between Western fast-food restaurants and body weight status. Results vary across study contexts and are sensitive to the samples, measures and methods used. Most studies have failed to examine the temporally dynamic associations between community exposure to fast-food restaurants and weight changes. Bayesian hierarchical regressions are used to model changes in body mass index, waist-to-height ratio (WHtR) and waist-to-hip ratio (WHpR) as a function of changes in Western fast-food restaurants in 216 communities for more than 9000 Chinese adults followed up multiple times between 2000 and 2009. Number of Western fast-food restaurants is positively associated with subsequent increases in WHtR and WHpR among rural population. More fast-food restaurants are positively associated with a future increase in WHpR for urban women. Increased availability of fast food between two waves is related to increased WHtR for urban men over the same period. A past increase in number of fast-food restaurants is associated with subsequent increases in WHtR and WHpR for rural population. The associations between community exposure to Western fast food and weight changes are temporally dynamic rather than static. Improved measures of exposure to community environment are needed to achieve more precise estimates and better understanding of these relationships. In light of the findings in this study and China's rapid economic growth, further investigation and increased public health monitoring is warranted since Western fast food is likely to be more accessible and affordable in the near future.

  9. Petascale molecular dynamics simulation using the fast multipole method on K computer

    Ohno, Yousuke; Yokota, Rio; Koyama, Hiroshi; Morimoto, Gentaro; Hasegawa, Aki; Masumoto, Gen; Okimoto, Noriaki; Hirano, Yoshinori; Ibeid, Huda; Narumi, Tetsu; Taiji, Makoto

    2014-01-01

    In this paper, we report all-atom simulations of molecular crowding - a result from the full node simulation on the "K computer", which is a 10-PFLOPS supercomputer in Japan. The capability of this machine enables us to perform simulation of crowded cellular environments, which are more realistic compared to conventional MD simulations where proteins are simulated in isolation. Living cells are "crowded" because macromolecules comprise ∼30% of their molecular weight. Recently, the effects of crowded cellular environments on protein stability have been revealed through in-cell NMR spectroscopy. To measure the performance of the "K computer", we performed all-atom classical molecular dynamics simulations of two systems: target proteins in a solvent, and target proteins in an environment of molecular crowders that mimic the conditions of a living cell. Using the full system, we achieved 4.4 PFLOPS during a 520 million-atom simulation with cutoff of 28 Å. Furthermore, we discuss the performance and scaling of fast multipole methods for molecular dynamics simulations on the "K computer", as well as comparisons with Ewald summation methods. © 2014 Elsevier B.V. All rights reserved.

  10. Implementation of a fast 16-Bit dynamic clamp using LabVIEW-RT.

    Kullmann, Paul H M; Wheeler, Diek W; Beacom, Joshua; Horn, John P

    2004-01-01

    The dynamic-clamp method provides a powerful electrophysiological tool for creating virtual ionic conductances in living cells and studying their influence on membrane potential. Here we describe G-clamp, a new way to implement a dynamic clamp using the real-time version of the Lab-VIEW programming environment together with a Windows host, an embedded microprocessor that runs a real-time operating system and a multifunction data-acquisition board. The software includes descriptions of a fast voltage-dependent sodium conductance, delayed rectifier, M-type and A-type potassium conductances, and a leak conductance. The system can also read synaptic conductance waveforms from preassembled data files. These virtual conductances can be reliably implemented at speeds < or =43 kHz while simultaneously saving two channels of data with 16-bit precision. G-clamp also includes utilities for measuring current-voltage relations, synaptic strength, and synaptic gain. Taking an approach built on a commercially available software/hardware platform has resulted in a system that is easy to assemble and upgrade. In addition, the graphical programming structure of LabVIEW should make it relatively easy for others to adapt G-clamp for new experimental applications.

  11. Petascale molecular dynamics simulation using the fast multipole method on K computer

    Ohno, Yousuke

    2014-10-01

    In this paper, we report all-atom simulations of molecular crowding - a result from the full node simulation on the "K computer", which is a 10-PFLOPS supercomputer in Japan. The capability of this machine enables us to perform simulation of crowded cellular environments, which are more realistic compared to conventional MD simulations where proteins are simulated in isolation. Living cells are "crowded" because macromolecules comprise ∼30% of their molecular weight. Recently, the effects of crowded cellular environments on protein stability have been revealed through in-cell NMR spectroscopy. To measure the performance of the "K computer", we performed all-atom classical molecular dynamics simulations of two systems: target proteins in a solvent, and target proteins in an environment of molecular crowders that mimic the conditions of a living cell. Using the full system, we achieved 4.4 PFLOPS during a 520 million-atom simulation with cutoff of 28 Å. Furthermore, we discuss the performance and scaling of fast multipole methods for molecular dynamics simulations on the "K computer", as well as comparisons with Ewald summation methods. © 2014 Elsevier B.V. All rights reserved.

  12. Fast two-photon imaging of subcellular voltage dynamics in neuronal tissue with genetically encoded indicators.

    Chamberland, Simon; Yang, Helen H; Pan, Michael M; Evans, Stephen W; Guan, Sihui; Chavarha, Mariya; Yang, Ying; Salesse, Charleen; Wu, Haodi; Wu, Joseph C; Clandinin, Thomas R; Toth, Katalin; Lin, Michael Z; St-Pierre, François

    2017-07-27

    Monitoring voltage dynamics in defined neurons deep in the brain is critical for unraveling the function of neuronal circuits but is challenging due to the limited performance of existing tools. In particular, while genetically encoded voltage indicators have shown promise for optical detection of voltage transients, many indicators exhibit low sensitivity when imaged under two-photon illumination. Previous studies thus fell short of visualizing voltage dynamics in individual neurons in single trials. Here, we report ASAP2s, a novel voltage indicator with improved sensitivity. By imaging ASAP2s using random-access multi-photon microscopy, we demonstrate robust single-trial detection of action potentials in organotypic slice cultures. We also show that ASAP2s enables two-photon imaging of graded potentials in organotypic slice cultures and in Drosophila . These results demonstrate that the combination of ASAP2s and fast two-photon imaging methods enables detection of neural electrical activity with subcellular spatial resolution and millisecond-timescale precision.

  13. Fast analysis of molecular dynamics trajectories with graphics processing units-Radial distribution function histogramming

    Levine, Benjamin G.; Stone, John E.; Kohlmeyer, Axel

    2011-01-01

    The calculation of radial distribution functions (RDFs) from molecular dynamics trajectory data is a common and computationally expensive analysis task. The rate limiting step in the calculation of the RDF is building a histogram of the distance between atom pairs in each trajectory frame. Here we present an implementation of this histogramming scheme for multiple graphics processing units (GPUs). The algorithm features a tiling scheme to maximize the reuse of data at the fastest levels of the GPU's memory hierarchy and dynamic load balancing to allow high performance on heterogeneous configurations of GPUs. Several versions of the RDF algorithm are presented, utilizing the specific hardware features found on different generations of GPUs. We take advantage of larger shared memory and atomic memory operations available on state-of-the-art GPUs to accelerate the code significantly. The use of atomic memory operations allows the fast, limited-capacity on-chip memory to be used much more efficiently, resulting in a fivefold increase in performance compared to the version of the algorithm without atomic operations. The ultimate version of the algorithm running in parallel on four NVIDIA GeForce GTX 480 (Fermi) GPUs was found to be 92 times faster than a multithreaded implementation running on an Intel Xeon 5550 CPU. On this multi-GPU hardware, the RDF between two selections of 1,000,000 atoms each can be calculated in 26.9 s per frame. The multi-GPU RDF algorithms described here are implemented in VMD, a widely used and freely available software package for molecular dynamics visualization and analysis.

  14. Ignoring detailed fast-changing dynamics of land use overestimates regional terrestrial carbon sequestration

    S. Q. Zhao

    2009-08-01

    Full Text Available Land use change is critical in determining the distribution, magnitude and mechanisms of terrestrial carbon budgets at the local to global scales. To date, almost all regional to global carbon cycle studies are driven by a static land use map or land use change statistics with decadal time intervals. The biases in quantifying carbon exchange between the terrestrial ecosystems and the atmosphere caused by using such land use change information have not been investigated. Here, we used the General Ensemble biogeochemical Modeling System (GEMS, along with consistent and spatially explicit land use change scenarios with different intervals (1 yr, 5 yrs, 10 yrs and static, respectively, to evaluate the impacts of land use change data frequency on estimating regional carbon sequestration in the southeastern United States. Our results indicate that ignoring the detailed fast-changing dynamics of land use can lead to a significant overestimation of carbon uptake by the terrestrial ecosystem. Regional carbon sequestration increased from 0.27 to 0.69, 0.80 and 0.97 Mg C ha−1 yr−1 when land use change data frequency shifting from 1 year to 5 years, 10 years interval and static land use information, respectively. Carbon removal by forest harvesting and prolonged cumulative impacts of historical land use change on carbon cycle accounted for the differences in carbon sequestration between static and dynamic land use change scenarios. The results suggest that it is critical to incorporate the detailed dynamics of land use change into local to global carbon cycle studies. Otherwise, it is impossible to accurately quantify the geographic distributions, magnitudes, and mechanisms of terrestrial carbon sequestration at the local to global scales.

  15. Fast computation of statistical uncertainty for spatiotemporal distributions estimated directly from dynamic cone beam SPECT projections

    Reutter, Bryan W.; Gullberg, Grant T.; Huesman, Ronald H.

    2001-01-01

    The estimation of time-activity curves and kinetic model parameters directly from projection data is potentially useful for clinical dynamic single photon emission computed tomography (SPECT) studies, particularly in those clinics that have only single-detector systems and thus are not able to perform rapid tomographic acquisitions. Because the radiopharmaceutical distribution changes while the SPECT gantry rotates, projections at different angles come from different tracer distributions. A dynamic image sequence reconstructed from the inconsistent projections acquired by a slowly rotating gantry can contain artifacts that lead to biases in kinetic parameters estimated from time-activity curves generated by overlaying regions of interest on the images. If cone beam collimators are used and the focal point of the collimators always remains in a particular transaxial plane, additional artifacts can arise in other planes reconstructed using insufficient projection samples [1]. If the projection samples truncate the patient's body, this can result in additional image artifacts. To overcome these sources of bias in conventional image based dynamic data analysis, we and others have been investigating the estimation of time-activity curves and kinetic model parameters directly from dynamic SPECT projection data by modeling the spatial and temporal distribution of the radiopharmaceutical throughout the projected field of view [2-8]. In our previous work we developed a computationally efficient method for fully four-dimensional (4-D) direct estimation of spatiotemporal distributions from dynamic SPECT projection data [5], which extended Formiconi's least squares algorithm for reconstructing temporally static distributions [9]. In addition, we studied the biases that result from modeling various orders temporal continuity and using various time samplings [5]. the present work, we address computational issues associated with evaluating the statistical uncertainty of

  16. Differentiation between benign and malignant colon tumors using fast dynamic gadolinium-enhanced MR colonography; a feasibility study

    Achiam, M P; Andersen, L P H; Klein, M

    2010-01-01

    Colorectal cancer will present itself as a bowel obstruction in 16-23% of all cases. However, not all obstructing tumors are malignant and the differentiation between a benign and a malignant tumor can be difficult. The purpose of our study was to determine whether fast dynamic gadolinium...

  17. Differentiation between benign and malignant colon tumors using fast dynamic gadolinium-enhanced MR colonography; a feasibility study

    Achiam, M P; Andersen, L P H; Klein, M

    2010-01-01

    Colorectal cancer will present itself as a bowel obstruction in 16-23% of all cases. However, not all obstructing tumors are malignant and the differentiation between a benign and a malignant tumor can be difficult. The purpose of our study was to determine whether fast dynamic gadolinium-enhance...

  18. Linearly scaling and almost Hamiltonian dielectric continuum molecular dynamics simulations through fast multipole expansions

    Lorenzen, Konstantin; Mathias, Gerald; Tavan, Paul, E-mail: tavan@physik.uni-muenchen.de [Lehrstuhl für BioMolekulare Optik, Ludig–Maximilians Universität München, Oettingenstr. 67, 80538 München (Germany)

    2015-11-14

    Hamiltonian Dielectric Solvent (HADES) is a recent method [S. Bauer et al., J. Chem. Phys. 140, 104103 (2014)] which enables atomistic Hamiltonian molecular dynamics (MD) simulations of peptides and proteins in dielectric solvent continua. Such simulations become rapidly impractical for large proteins, because the computational effort of HADES scales quadratically with the number N of atoms. If one tries to achieve linear scaling by applying a fast multipole method (FMM) to the computation of the HADES electrostatics, the Hamiltonian character (conservation of total energy, linear, and angular momenta) may get lost. Here, we show that the Hamiltonian character of HADES can be almost completely preserved, if the structure-adapted fast multipole method (SAMM) as recently redesigned by Lorenzen et al. [J. Chem. Theory Comput. 10, 3244-3259 (2014)] is suitably extended and is chosen as the FMM module. By this extension, the HADES/SAMM forces become exact gradients of the HADES/SAMM energy. Their translational and rotational invariance then guarantees (within the limits of numerical accuracy) the exact conservation of the linear and angular momenta. Also, the total energy is essentially conserved—up to residual algorithmic noise, which is caused by the periodically repeated SAMM interaction list updates. These updates entail very small temporal discontinuities of the force description, because the employed SAMM approximations represent deliberately balanced compromises between accuracy and efficiency. The energy-gradient corrected version of SAMM can also be applied, of course, to MD simulations of all-atom solvent-solute systems enclosed by periodic boundary conditions. However, as we demonstrate in passing, this choice does not offer any serious advantages.

  19. Slow-fast stochastic diffusion dynamics and quasi-stationarity for diploid populations with varying size.

    Coron, Camille

    2016-01-01

    We are interested in the long-time behavior of a diploid population with sexual reproduction and randomly varying population size, characterized by its genotype composition at one bi-allelic locus. The population is modeled by a 3-dimensional birth-and-death process with competition, weak cooperation and Mendelian reproduction. This stochastic process is indexed by a scaling parameter K that goes to infinity, following a large population assumption. When the individual birth and natural death rates are of order K, the sequence of stochastic processes indexed by K converges toward a new slow-fast dynamics with variable population size. We indeed prove the convergence toward 0 of a fast variable giving the deviation of the population from quasi Hardy-Weinberg equilibrium, while the sequence of slow variables giving the respective numbers of occurrences of each allele converges toward a 2-dimensional diffusion process that reaches (0,0) almost surely in finite time. The population size and the proportion of a given allele converge toward a Wright-Fisher diffusion with stochastically varying population size and diploid selection. We insist on differences between haploid and diploid populations due to population size stochastic variability. Using a non trivial change of variables, we study the absorption of this diffusion and its long time behavior conditioned on non-extinction. In particular we prove that this diffusion starting from any non-trivial state and conditioned on not hitting (0,0) admits a unique quasi-stationary distribution. We give numerical approximations of this quasi-stationary behavior in three biologically relevant cases: neutrality, overdominance, and separate niches.

  20. Dynamic gene expression in fish muscle during recovery growth induced by a fasting-refeeding schedule

    Esquerré Diane

    2007-11-01

    Full Text Available Abstract Background Recovery growth is a phase of rapid growth that is triggered by adequate refeeding of animals following a period of weight loss caused by starvation. In this study, to obtain more information on the system-wide integration of recovery growth in muscle, we undertook a time-course analysis of transcript expression in trout subjected to a food deprivation-refeeding sequence. For this purpose complex targets produced from muscle of trout fasted for one month and from muscle of trout fasted for one month and then refed for 4, 7, 11 and 36 days were hybridized to cDNA microarrays containing 9023 clones. Results Significance analysis of microarrays (SAM and temporal expression profiling led to the segregation of differentially expressed genes into four major clusters. One cluster comprising 1020 genes with high expression in muscle from fasted animals included a large set of genes involved in protein catabolism. A second cluster that included approximately 550 genes with transient induction 4 to 11 days post-refeeding was dominated by genes involved in transcription, ribosomal biogenesis, translation, chaperone activity, mitochondrial production of ATP and cell division. A third cluster that contained 480 genes that were up-regulated 7 to 36 days post-refeeding was enriched with genes involved in reticulum and Golgi dynamics and with genes indicative of myofiber and muscle remodelling such as genes encoding sarcomeric proteins and matrix compounds. Finally, a fourth cluster of 200 genes overexpressed only in 36-day refed trout muscle contained genes with function in carbohydrate metabolism and lipid biosynthesis. Remarkably, among the genes induced were several transcriptional regulators which might be important for the gene-specific transcriptional adaptations that underlie muscle recovery. Conclusion Our study is the first demonstration of a coordinated expression of functionally related genes during muscle recovery growth

  1. A fast chaos-based image encryption scheme with a dynamic state variables selection mechanism

    Chen, Jun-xin; Zhu, Zhi-liang; Fu, Chong; Yu, Hai; Zhang, Li-bo

    2015-03-01

    In recent years, a variety of chaos-based image cryptosystems have been investigated to meet the increasing demand for real-time secure image transmission. Most of them are based on permutation-diffusion architecture, in which permutation and diffusion are two independent procedures with fixed control parameters. This property results in two flaws. (1) At least two chaotic state variables are required for encrypting one plain pixel, in permutation and diffusion stages respectively. Chaotic state variables produced with high computation complexity are not sufficiently used. (2) The key stream solely depends on the secret key, and hence the cryptosystem is vulnerable against known/chosen-plaintext attacks. In this paper, a fast chaos-based image encryption scheme with a dynamic state variables selection mechanism is proposed to enhance the security and promote the efficiency of chaos-based image cryptosystems. Experimental simulations and extensive cryptanalysis have been carried out and the results prove the superior security and high efficiency of the scheme.

  2. Effect of coupling currents on the dynamic inductance during fast transient in superconducting magnets

    V. Marinozzi

    2015-03-01

    Full Text Available We present electromagnetic models aiming to calculate the variation of the inductance in a magnet due to dynamic effects such as the variation of magnetization or the coupling with eddy currents. The models are studied with special regard to the calculation of the inductance in superconducting magnets which are affected by interfilament coupling currents. The developed models have been compared with experimental data coming from tests of prototype Nb_{3}Sn magnets designed for the new generation of accelerators. This work is relevant for the quench protection study of superconducting magnets: quench is an unwanted event, when part of the magnet becomes resistive; in these cases, the current should be discharged as fast as possible, in order to maintain the resistive zone temperature under a safe limit. The magnet inductance is therefore a relevant term for the description of the current discharge, especially for the high-field new generation superconducting magnets for accelerators, and this work shows how to calculate the correct value during rapid current changes, providing a mean for simulations of the reached temperature.

  3. Effects of slow and fast pyrolysis biochar on soil C and N turnover dynamics

    Bruun, Esben; Ambus, Per; Egsgaard, Helge

    2012-01-01

    This study compared the effect of two principal pyrolysis methods on the chemical characteristics of biochar and the impact on C and N dynamics after soil incorporation. Biochar was produced from wheat straw that was thermally decomposed at 525 °C by slow pyrolysis (SP) in a nitrogen flushed oven...... and by fast pyrolysis (FP) using a Pyrolysis Centrifuge Reactor (PCR). After 65 days of soil incubation, 2.9% and 5.5% of the SP- and FP-biochar C, respectively, was lost as CO2, significantly less than the 53% C-loss observed when un-pyrolyzed feedstock straw was incubated. Whereas the SP-biochar appeared...... completely pyrolyzed, an un-pyrolyzed carbohydrate fraction (8.8% as determined by acid released C6 and C5 sugars) remained in the FP-biochar. This labile fraction possibly supported the higher CO2 emission and larger microbial biomass (SMB-C) in the FP-biochar soil. Application of fresh FP-biochar to soil...

  4. Fast Optimal Replica Placement with Exhaustive Search Using Dynamically Reconfigurable Processor

    Hidetoshi Takeshita

    2011-01-01

    Full Text Available This paper proposes a new replica placement algorithm that expands the exhaustive search limit with reasonable calculation time. It combines a new type of parallel data-flow processor with an architecture tuned for fast calculation. The replica placement problem is to find a replica-server set satisfying service constraints in a content delivery network (CDN. It is derived from the set cover problem which is known to be NP-hard. It is impractical to use exhaustive search to obtain optimal replica placement in large-scale networks, because calculation time increases with the number of combinations. To reduce calculation time, heuristic algorithms have been proposed, but it is known that no heuristic algorithm is assured of finding the optimal solution. The proposed algorithm suits parallel processing and pipeline execution and is implemented on DAPDNA-2, a dynamically reconfigurable processor. Experiments show that the proposed algorithm expands the exhaustive search limit by the factor of 18.8 compared to the conventional algorithm search limit running on a Neumann-type processor.

  5. Nutrients dynamics of co-composting poultry litter with fast food wastes

    Hayat, A.; Chaudhary, A.N.

    2015-01-01

    Co-composting of poultry litter (PL) and fast food waste (FFW) in different combinations was carried out to explore the nutrient dynamics. The PL and FFW were co-composted in pits of dimensions 2 m*2 m*1.5 m (L*W*D) in ratios of 100:0, 75:25, 50:50, 25:75 and 0:100, respectively, for a period of 105 days. Co-composts of PL and FFW in a 50:50 ratio yielded highest total nitrogen (3.63%), total phosphorus (0.81%), and total potassium (3.40%) levels in the mature compost after 105 days of composting period. Carbon to nitrogen ratio for this combination was 18.33, which is suitable for safe land application. Present study identified PL and FFW co-composting in equal proportions yields maximum N, P and K levels with suitable C:N ratio which may be applied to soils to meet crop nutrient demands and enhanced agricultural productivity. (author)

  6. Dynamics of local isolated magnetic flux tubes in a fast-rotating stellar atmosphere

    Chou, W.; Tajima, C.T.; Shibata, K.

    1998-01-01

    Dynamics of magnetic flux tubes in the fast rotating stellar atmosphere is studied. We focus on the effects and signatures of the instability of the flux tube emergence influenced by the Coriolis force. We present the result from a linear stability analysis and discuss its possible signatures in the course of the evolution of G-type and M-type stars. We present a three dimensional magnetohydrodynamical simulation of local isolated magnetic flux tubes under a magnetic buoyancy instability in co-rotating Cartesian coordinates. We find that the combination of the buoyancy instability and the Coriolis effect gives rise to a mechanism, to twist the emerging magnetic flux tube into a helical structure. The tilt angle, east-west asymmetry and magnetic helicity of the Twisted flux tubes in the simulations are studied in detail. The linear and nonlinear analyses provide hints as to what kind of pattern of large spots in young M-type main-sequence stars might be observed. We find that young and old G-type stars may have different distributions of spots while M-type stars may always have low latitudes spots. The size of stellar spots may decrease when a star becomes older, due to the decreasing of magnetic field. A qualitative comparison with solar observations is also presented

  7. Fast ion dynamics in ASDEX upgrade and TEXTOR measured by collective Thomson scattering

    Moseev, D.

    2011-11-01

    Fast ions are an essential ingredient in burning nuclear fusion plasmas: they are responsible for heating the bulk plasma, carry a significant amount of plasma current and moreover interact with various magnetohydrodynamic (MHD) instabilities. The collective Thomson scattering (CTS) diagnostic is sensitive to the projection of fast ion velocity distribution function. This thesis is mainly devoted to investigations of fast ion physics in tokamak plasmas by means of CTS. (Author)

  8. Fast ion dynamics in ASDEX upgrade and TEXTOR measured by collective Thomson scattering

    Moseev, D.

    2011-11-15

    Fast ions are an essential ingredient in burning nuclear fusion plasmas: they are responsible for heating the bulk plasma, carry a significant amount of plasma current and moreover interact with various magnetohydrodynamic (MHD) instabilities. The collective Thomson scattering (CTS) diagnostic is sensitive to the projection of fast ion velocity distribution function. This thesis is mainly devoted to investigations of fast ion physics in tokamak plasmas by means of CTS. (Author)

  9. Modeling in fast dynamics of accidents in the primary circuit of PWR type reactors

    Robbe, M.F.

    2003-12-01

    Two kinds of accidents, liable to occur in the primary circuit of a Pressurized Water Reactor and involving fast dynamic phenomena, are analyzed. The Loss Of Coolant Accident (LOCA) is the accident used to define the current PWR. It consists in a large-size break located in a pipe of the primary circuit. A blowdown wave propagates through the circuit. The pressure differences between the different zones of the reactor induce high stresses in the structures of the lower head and may degrade the reactor core. The primary circuit starts emptying from the break opening. Pressure decreases very quickly, involving a large steaming. Two thermal-hydraulic simulations of the blowdown phase of a LOCA are computed with the Europlexus code. The primary circuit is represented by a pipe-model including the hydraulic peculiarities of the circuit. The main differences between both computations concern the kind of reactor, the break location and model, and the initialization of the accidental operation. Steam explosion is a hypothetical severe accident liable to happen after a core melting. The molten part of the core (called corium) falls in the lower part of the reactor. The interaction between the hot corium and the cold water remaining at the bottom of the vessel induces a massive and violent vaporization of water, similar to an explosive phenomenon. A shock wave propagates in the vessel. what can damage seriously the neighbouring structures or drill the vessel. This work presents a synthesis of in-vessel parametrical studies carried out with the Europlexus code, the linkage of the thermal-hydraulic code Mc3d dedicated to the pre-mixing phase with the Europlexus code dealing with the explosion, and finally a benchmark between the Cigalon and Europlexus codes relative to the Vulcano mock-up. (author)

  10. Plasma sheet fast flows and auroral dynamics during substorm: a case study

    N. L. Borodkova

    2002-03-01

    Full Text Available Interball-1 observations of a substorm development in the mid-tail on 16 December 1998 are compared with the auroral dynamics obtained from the Polar UV imager. Using these data, the relationship between plasma flow directions in the tail and the location of the auroral activation is examined. Main attention is given to tailward and earth-ward plasma flows, interpreted as signatures of a Near Earth Neutral Line (NENL. It is unambiguously shown that in the mid-plasma sheet the flows were directed tailward when the auroral bulge developed equatorward of the spacecraft ionospheric footprint. On the contrary, when active auroras moved poleward of the Interball-1 projection, earthward fast flow bursts were observed. This confirms the concept that the NENL (or flow reversal region is the source of auroras forming the poleward edge of the auroral bulge. The observed earthward flow bursts have all typical signatures of Bursty Bulk Flows (BBFs, described by Angelopolous et al. (1992. These BBFs are related to substorm activations starting at the poleward edge of the expanded auroral bulge. We interpret the BBFs as a result of reconnection pulses occurring tail-ward of Interball-1. In addition, some non-typically observed phenomena were detected in the plasma sheet during this substorm: (i tailward/earthward flows were superimposed on a very strong duskward flow, and (ii wavy structures of both magnetic field and plasma density were registered. The latter observation is probably linked to the filamentary structure of the current sheet.Key words. Magnetospheric physics (auroral phenomena; plasma sheet; storms and substorms

  11. Dynamics analysis of the fast-slow hydro-turbine governing system with different time-scale coupling

    Zhang, Hao; Chen, Diyi; Wu, Changzhi; Wang, Xiangyu

    2018-01-01

    Multi-time scales modeling of hydro-turbine governing system is crucial in precise modeling of hydropower plant and provides support for the stability analysis of the system. Considering the inertia and response time of the hydraulic servo system, the hydro-turbine governing system is transformed into the fast-slow hydro-turbine governing system. The effects of the time-scale on the dynamical behavior of the system are analyzed and the fast-slow dynamical behaviors of the system are investigated with different time-scale. Furthermore, the theoretical analysis of the stable regions is presented. The influences of the time-scale on the stable region are analyzed by simulation. The simulation results prove the correctness of the theoretical analysis. More importantly, the methods and results of this paper provide a perspective to multi-time scales modeling of hydro-turbine governing system and contribute to the optimization analysis and control of the system.

  12. Fast pulsing dynamics of a vertical-cavity surface-emitting laser operating in the low-frequency fluctuation regime

    Sciamanna, M.; Rogister, F.; Megret, P.; Blondel, M.; Masoller, C.; Abraham, N. B.

    2003-01-01

    We analyze the dynamics of a vertical-cavity surface-emitting laser with optical feedback operating in the low-frequency fluctuation regime. By focusing on the fast pulsing dynamics, we show that the two linearly polarized modes of the laser exhibit two qualitatively different behaviors: they emit pulses in phase just after a power dropout and they emit pulses out of phase after the recovery process of the output power. As a consequence, two distinct statistical distributions of the fast pulsating total intensity are observed, either monotonically decaying from the noise level or peaked around the mean intensity value. We further show that gain self-saturation of the lasing transition strongly modifies the shape of the intensity distribution

  13. Attractors of relaxation discrete-time systems with chaotic dynamics on a fast time scale

    Maslennikov, Oleg V.; Nekorkin, Vladimir I.

    2016-01-01

    In this work, a new type of relaxation systems is considered. Their prominent feature is that they comprise two distinct epochs, one is slow regular motion and another is fast chaotic motion. Unlike traditionally studied slow-fast systems that have smooth manifolds of slow motions in the phase space and fast trajectories between them, in this new type one observes, apart the same geometric objects, areas of transient chaos. Alternating periods of slow regular motions and fast chaotic ones as well as transitions between them result in a specific chaotic attractor with chaos on a fast time scale. We formulate basic properties of such attractors in the framework of discrete-time systems and consider several examples. Finally, we provide an important application of such systems, the neuronal electrical activity in the form of chaotic spike-burst oscillations.

  14. High-definition velocity-space tomography of fast-ion dynamics

    Salewski, Mirko; Geiger, B.; Jacobsen, A.S.

    2016-01-01

    Velocity-space tomography of the fast-ion distribution function in a fusion plasma is usually a photon-starved tomography method due to limited optical access and signal-to-noise ratio of fast-ion Dα (FIDA) spectroscopy as well as the strive for high-resolution images. In high-definition tomography...... information to reconstruct where in velocity space the measurements and the simulation disagree. This alternative approach is demonstrated for four-view as well as for two-view FIDA measurements. The high-definition tomography tools allow us to study fast ions in sawtoothing plasmas and the formation of NBI...

  15. Modeling HIV-1 intracellular replication: two simulation approaches

    Zarrabi, N.; Mancini, E.; Tay, J.; Shahand, S.; Sloot, P.M.A.

    2010-01-01

    Many mathematical and computational models have been developed to investigate the complexity of HIV dynamics, immune response and drug therapy. However, there are not many models which consider the dynamics of virus intracellular replication at a single level. We propose a model of HIV intracellular

  16. Plasticization effect of C60 on the fast dynamics of polystyrene and related polymers: an incoherent neutron scattering study

    Sanz, Alejandro; Ruppel, Markus; Cabral, Joao T; Douglas, Jack F

    2008-01-01

    We utilize inelastic incoherent neutron scattering (INS) to quantify how fullerenes affect the 'fast' molecular dynamics of a family of polystyrene related macromolecules. In particular, we prepared bulk nanocomposites of (hydrogenous and ring-deuterated) polystyrene and poly(4-methyl styrene) using a rapid precipitation method where the C 60 relative mass fraction ranged from 0% to 4%. Elastic window scan measurements, using a high resolution (0.9 μeV) backscattering spectrometer, are reported over a wide temperature range (2-450 K). Apparent Debye-Waller (DW) factors 2 >, characterizing the mean-square amplitude of proton displacements, are determined as a function of temperature, T. We find that the addition of C 60 to these polymers leads to a progressive increase in 2 > relative to the pure polymer value over the entire temperature range investigated, where the effect is larger for larger nanoparticle concentration. This general trend seems to indicate that the C 60 nanoparticles plasticize the fast (∼10 -15 s) local (∼1 A) dynamics of these polymer glasses. Generally, we expect nanoparticle additives to affect polymer dynamics in a similar fashion to thin films in the sense that the high interfacial area may cause both a speeding up and slowing down of the glass state dynamics depending on the polymer-surface interaction

  17. Extending the Capabilities of the Mooring Analysis Program: A Survey of Dynamic Mooring Line Theories for Integration into FAST: Preprint

    Masciola, M.; Jonkman, J.; Robertson, A.

    2014-03-01

    Techniques to model dynamic mooring lines come in various forms. The most widely used models include either a heuristic representation of the physics (such as a Lumped-Mass, LM, system), a Finite-Element Analysis (FEA) discretization of the lines (discretized in space), or a Finite-Difference (FD) model (which is discretized in both space and time). In this paper, we explore the features of the various models, weigh the advantages of each, and propose a plan for implementing one dynamic mooring line model into the open-source Mooring Analysis Program (MAP). MAP is currently used as a module for the FAST offshore wind turbine computer-aided engineering (CAE) tool to model mooring systems quasi-statically, although dynamic mooring capabilities are desired. Based on the exploration in this manuscript, the lumped-mass representation is selected for implementation in MAP based on its simplicity, computational cost, and ability to provide similar physics captured by higher-order models.

  18. 3D Dynamic Modeling of the Head-Neck Complex for Fast Eye and Head Orientation Movements Research

    Daniel A. Sierra

    2011-01-01

    Full Text Available A 3D dynamic computer model for the movement of the head-neck complex is presented. It incorporates anatomically correct information about the diverse elements forming the system. The skeleton is considered as a set of interconnected rigid 3D bodies following the Newton-Euler laws of movement. The muscles are modeled using Enderle's linear model, which shows equivalent dynamic characteristics to Loeb's virtual muscle model. The soft tissues, namely, the ligaments, intervertebral disks, and facet joints, are modeled considering their physiological roles and dynamics. In contrast with other head and neck models developed for safety research, the model is aimed to study the neural control of the complex during fast eye and head movements, such as saccades and gaze shifts. In particular, the time-optimal hypothesis and the feedback control ones are discussed.

  19. Applying System Dynamics Approach to the Fast Fashion Supply Chain: Case Study of an SME in Indonesia

    Mariany W Lidia

    2012-09-01

    Full Text Available The fashion industry is the biggest contributor among the 14 creative industries in Indonesia. Nowadays many apparel companies are shifting toward the vertical integration. Since speed is everything to be successful in the apparel industry, fast fashion retailers must quickly respond to the market demand. This papers aims to develop a model of the supply chain of a small and medium scale enterprise (SME of an apparel company in Indonesia and to propose a decision support system using System Dynamics (SD and helps the management to identify the best business strategy. Simulated scenarios can help the management to identify the most appropriate policy to be applied in the future. Case study method was used in this research where data were collected from a typical fast fashion firm in Indonesia that produces its own wares ranging from raw materials to be ready-to-wear clothes, has three stores, a warehouse and is running online sales system. We analyses the result of many simulations in a fashion company from an operational point of view and from them we derive suggestions about the future business strategy in a small and medium fashion company in Indonesia. Keywords: system dynamics, fast fashion, supply chain management, SME, Indonesia

  20. Cortical networks dynamically emerge with the interplay of slow and fast oscillations for memory of a natural scene.

    Mizuhara, Hiroaki; Sato, Naoyuki; Yamaguchi, Yoko

    2015-05-01

    Neural oscillations are crucial for revealing dynamic cortical networks and for serving as a possible mechanism of inter-cortical communication, especially in association with mnemonic function. The interplay of the slow and fast oscillations might dynamically coordinate the mnemonic cortical circuits to rehearse stored items during working memory retention. We recorded simultaneous EEG-fMRI during a working memory task involving a natural scene to verify whether the cortical networks emerge with the neural oscillations for memory of the natural scene. The slow EEG power was enhanced in association with the better accuracy of working memory retention, and accompanied cortical activities in the mnemonic circuits for the natural scene. Fast oscillation showed a phase-amplitude coupling to the slow oscillation, and its power was tightly coupled with the cortical activities for representing the visual images of natural scenes. The mnemonic cortical circuit with the slow neural oscillations would rehearse the distributed natural scene representations with the fast oscillation for working memory retention. The coincidence of the natural scene representations could be obtained by the slow oscillation phase to create a coherent whole of the natural scene in the working memory. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Effects of fast monoenergetic electrons on the ion dynamics near the cathode in a pulsed direct current plasma sheath

    Sharifian, M.; Shokri, B.

    2008-01-01

    A detailed one-dimensional simulation of the ion dynamics of the plasma sheath near a substrate (cathode) in the presence of fast monoenergetic electrons has been carried out in this article. The sheath evolution is investigated by using a fluid model assuming that the ions, plasma electrons and monoenergetic, fast electrons act as three fluids (fluid approach). The effect of the density of fast electrons on the ion density, ion velocity, and ion energy near the cathode and the evolution of the sheath boundary in front of the cathode are separately explored. Also, the variation of the ion velocity and ion density at the vicinity of the cathode as a function of time is investigated in the absence and presence of the electron beam. Results indicate that the presence of fast electrons in the sheath causes significant change in the sheath thickness and therefore basically changes the ion velocity, ion density, and ion impact energy on the cathode compared to the absence of the electron beam case

  2. Distinct slow and fast cortical theta dynamics in episodic memory retrieval.

    Pastötter, Bernhard; Bäuml, Karl-Heinz T

    2014-07-01

    Brain oscillations in the theta frequency band (3-8 Hz) have been shown to be critically involved in human episodic memory retrieval. In prior work, both positive and negative relationships between cortical theta power and retrieval success have been reported. This study examined the hypothesis that slow and fast cortical theta oscillations at the edges of the traditional theta frequency band are differentially related to retrieval success. Scalp EEG was recorded in healthy human participants as they performed a cued-recall episodic memory task. Slow (~3 Hz) and fast (~7 Hz) theta oscillations at retrieval were examined as a function of whether an item was recalled or not and as a function of the items' output position at test. Recall success typically declines with output position, due to increases in interference level. The results showed that slow theta power was positively related but fast theta power was negatively related to retrieval success. Concurrent positive and negative episodic memory effects for slow and fast theta oscillations were dissociable in time and space, showing different time courses and different spatial locations on the scalp. Moreover, fast theta power increased from early to late output positions, whereas slow theta power was unaffected by items' output position. Together with prior work, the results suggest that slow and fast theta oscillations have distinct functional roles in episodic memory retrieval, with slow theta oscillations being related to processes of recollection and conscious awareness, and fast theta oscillations being linked to processes of interference and interference resolution. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Contrast-enhanced magnetic resonance imaging of the breast: the value of pharmacokinetic parameters derived from fast dynamic imaging during initial enhancement in classifying lesions

    Veltman, J.; Stoutjesdijk, M.; Mann, R.; Huisman, H.J.; Barentsz, J.O.; Blickman, J.G.; Boetes, C.

    2008-01-01

    The value of pharmacokinetic parameters derived from fast dynamic imaging during initial enhancement in characterizing breast lesions on magnetic resonance imaging (MRI) was evaluated. Sixty-eight malignant and 34 benign lesions were included. In the scanning protocol, high temporal resolution imaging was combined with high spatial resolution imaging. The high temporal resolution images were recorded every 4.1 s during initial enhancement (fast dynamic analysis). The high spatial resolution images were recorded at a temporal resolution of 86 s (slow dynamic analysis). In the fast dynamic evaluation pharmacokinetic parameters (K trans , V e and k ep ) were evaluated. In the slow dynamic analysis, each lesion was scored according to the BI-RADS classification. Two readers evaluated all data prospectively. ROC and multivariate analysis were performed. The slow dynamic analysis resulted in an AUC of 0.85 and 0.83, respectively. The fast dynamic analysis resulted in an AUC of 0.83 in both readers. The combination of both the slow and fast dynamic analyses resulted in a significant improvement of diagnostic performance with an AUC of 0.93 and 0.90 (P = 0.02). The increased diagnostic performance found when combining both methods demonstrates the additional value of our method in further improving the diagnostic performance of breast MRI. (orig.)

  4. Dynamic mechanical properties of polymer blends of polypropylene and poly(ethylene-co-vinyl acetate) irradiated with fast electrons

    Mihaylova, M.; Kresteva, M.; Perena, J; Phillips, P.

    2001-01-01

    Extruded blends of polypropylene and poly(ethylene-co-vinyl acetate) irradiated with fast electrons were studied. The dynamic mechanical properties were investigated with respects to the blend composition and irradiation dose. Two glass transition temperatures corresponding to the glass transitions of the pure components were observed. Their existence is an evidence of immiscibility of the components. Nevertheless, the peaks broadening, the single jump in the storage modulus values and the changes of T g with the blend ratio suggest the creation of an interface region, leading to the improvement of the compatibility of the components. The irradiation with fast electrons at doses higher than 100 KGy results in single T g transition because of the broadening of the interface layer. (authors)

  5. Fast, high-fidelity, all-optical and dynamically-controlled polarization gate using room-temperature atomic vapor

    Li, Runbing [National Institute of Standards and Technology, Gaithersburg, Maryland 20899 (United States); State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Center for Cold Atom Physics, Chinese Academy of Sciences, Wuhan 430071 (China); Zhu, Chengjie [National Institute of Standards and Technology, Gaithersburg, Maryland 20899 (United States); School of Physics Science and Engineering, Tongji University, Shanghai 200092 (China); Deng, L.; Hagley, E. W. [National Institute of Standards and Technology, Gaithersburg, Maryland 20899 (United States)

    2014-10-20

    We demonstrate a fast, all-optical polarization gate in a room-temperature atomic medium. Using a Polarization-Selective-Kerr-Phase-Shift (PSKPS) technique, we selectively write a π phase shift to one circularly-polarized component of a linearly-polarized input signal field. The output signal field maintains its original strength but acquires a 90° linear polarization rotation, demonstrating fast, high-fidelity, dynamically-controlled polarization gate operation. The intensity of the polarization-switching field used in this PKSPK-based polarization gate operation is only 2 mW/cm{sup 2}, which would be equivalent to 0.5 nW of light power (λ = 800 nm) confined in a typical commercial photonic hollow-core fiber. This development opens a realm of possibilities for potential future extremely low light level telecommunication and information processing systems.

  6. Carnivora population dynamics are as slow and as fast as those of other mammals

    van de Kerk, Madelon; de Kroon, Hans; Jongejans, Eelke

    2013-01-01

    in triangular elasticity plots as those of other mammal species, despite the specific place of Carnivora in the food chain. Furthermore, reproductive loop elasticity analysis shows that the studied species spread out evenly over a slow-fast continuum, but also quantifies the large variation in the duration...... to unstudied species. With several examples we discuss how this slow-fast continuum, and related patterns of variation in reproductive loop elasticity, can be used in the formulation of tentative management plans for threatened species that cannot wait for the results of thorough demographic studies. We argue...

  7. A fast network solution by the decoupled procedure during short-term dynamic processes in power systems

    Popovic, D P; Stefanovic, M D [Nikola Tesla Inst., Belgrade (YU). Power System Dept.

    1990-01-01

    A simple, fast and reliable decoupled procedure for solving the network problems during short-term dynamic processes in power systems is presented. It is based on the Newton-Raphson method applied to the power balance equations, which include the effects of generator saliency and non-impedance loads, with further modifications resulting from the physical properties of the phenomena under study. The good convergence characteristics of the developed procedure are demonstrated, and a comparison is made with the traditional method based on the current equation and the triangularized admittance matrix, using the example of stability analysis of the Yugoslav power grid. (author).

  8. Ultra-fast x-ray tomography for multi-phase flow interface dynamic studies

    Misawa, M.; Ichikawa, N.; Akai, M.; Tiseanu, I.; Prasser, H.-M.

    2003-01-01

    The present paper describes the concept of a fast scanning X-ray tomograph, the hardware development, and measurement results of gas-liquid two-phase flow in a vertical pipe. The device uses 18 pulsed X-ray sources activated in a successive order. In this way, a complete set of 18 independent projections of the object is obtained within 38 ms, i.e. the measuring rate is about 250 frames per second. Finally, to evaluate the measurement capability of the fast X-ray CT, a wire-mesh sensor was installed in the flow loop and both systems were operated for the same two-phase flow simultaneously. Comparison of the time series of the cross section averaged void fraction from both systems showed sufficient agreement for slug flow at large void fractions, while the fast CT underestimated the void fraction of bubbly flow especially in low void fraction range. For the wire-mesh sensor, coerced deformation of slug bubble interface was found. Further hardware improvement is in progress to achieve better resolution with the fast X-ray CT scanner. (orig.)

  9. Fast and stable redox reactions of MnO2/CNT hybrid electrodes for dynamically stretchable pseudocapacitors

    Gu, Taoli; Wei, Bingqing

    2015-07-01

    Pseudocapacitors, which are energy storage devices that take advantage of redox reactions to store electricity, have a different charge storage mechanism compared to lithium-ion batteries (LIBs) and electric double-layer capacitors (EDLCs), and they could realize further gains if they were used as stretchable power sources. The realization of dynamically stretchable pseudocapacitors and understanding of the underlying fundamentals of their mechanical-electrochemical relationship have become indispensable. We report herein the electrochemical performance of dynamically stretchable pseudocapacitors using buckled MnO2/CNT hybrid electrodes. The extremely small relaxation time constant of less than 0.15 s indicates a fast redox reaction at the MnO2/CNT hybrid electrodes, securing a stable electrochemical performance for the dynamically stretchable pseudocapacitors. This finding and the fundamental understanding gained from the pseudo-capacitive behavior coupled with mechanical deformation under a dynamic stretching mode would provide guidance to further improve their overall performance including a higher power density than LIBs, a higher energy density than EDLCs, and a long-life cycling stability. Most importantly, these results will potentially accelerate the applications of stretchable pseudocapacitors for flexible and biomedical electronics.Pseudocapacitors, which are energy storage devices that take advantage of redox reactions to store electricity, have a different charge storage mechanism compared to lithium-ion batteries (LIBs) and electric double-layer capacitors (EDLCs), and they could realize further gains if they were used as stretchable power sources. The realization of dynamically stretchable pseudocapacitors and understanding of the underlying fundamentals of their mechanical-electrochemical relationship have become indispensable. We report herein the electrochemical performance of dynamically stretchable pseudocapacitors using buckled MnO2/CNT hybrid

  10. Rational design of reversible fluorescent probes for live-cell imaging and quantification of fast glutathione dynamics

    Umezawa, Keitaro; Yoshida, Masafumi; Kamiya, Mako; Yamasoba, Tatsuya; Urano, Yasuteru

    2017-03-01

    Alterations in glutathione (GSH) homeostasis are associated with a variety of diseases and cellular functions, and therefore, real-time live-cell imaging and quantification of GSH dynamics are important for understanding pathophysiological processes. However, existing fluorescent probes are unsuitable for these purposes due to their irreversible fluorogenic mechanisms or slow reaction rates. In this work, we have successfully overcome these problems by establishing a design strategy inspired by Mayr's work on nucleophilic reaction kinetics. The synthesized probes exhibit concentration-dependent, reversible and rapid absorption/fluorescence changes (t1/2 = 620 ms at [GSH] = 1 mM), as well as appropriate Kd values (1-10 mM: within the range of intracellular GSH concentrations). We also developed FRET-based ratiometric probes, and demonstrated that they are useful for quantifying GSH concentration in various cell types and also for real-time live-cell imaging of GSH dynamics with temporal resolution of seconds.

  11. Comparison of dynamic dual spin-echo and fast-gradient-echo techniques in the evaluation of cardiac diseases

    Pettigrew, R.I.; Eisner, R.L.; Groen, J.P.; Baron, M.G.

    1987-01-01

    To determine the relative roles of a dynamic spin-echo method and a fast acquisition with multiphase excitations (FAME) technique, ten patients with myocardial infarction (MI), five with myocardial masses, and five healthy patients were studied with both methods. The dynamic dual-spin-echo (DSE) technique allows acquisition of each of seven sections at 14 cardiac phases in 20 minutes. Wall motion abnormalities were seen equally well with both techniques, but FAME usually required a shorter study time (10 minutes). DSE, however, was superior for evaluating cardiac masses and provided superior wall blood contrast. Thus, these techniques are complementary, and both are now a routine part of the authors' study of cardiac patients

  12. Phosphorus dynamics and limitation of fast- and slow-growing temperate seaweeds in Oslofjord, Norway

    Pedersen, Morten Foldager; Borum, Jens; Fotel, Frank Leck

    2010-01-01

    During coastal eutrophication, fast-growing, ephemeral macroalgae bloom at the expense of slow-growing, perennial macroalgae. This change in community composition has been explained by a differential ability to exploit and utilize inorganic nitrogen among macroalgae with different growth strategies......-growing algae (Ulva and Ceramium) took up dissolved inorganic P (DIP) much faster than thicker, slower growing species (belonging to Fucus, Ascophyllum and Laminaria) but also had much higher P-demands per unit biomass and time. DIP concentrations in the Oslofjord were low from April through August, and fast......-growing species were unable to meet their P-demand from uptake for several months during summer. Hence, Ceramium and Ulva were potentially P-limited during summer, whereas Ascophyllum and Laminaria were able to acquire sufficient external DIP to remain P-replete throughout the year. Storage of P prevented Fucus...

  13. Calculation of the MT25 microtron dynamics and its fast simulation

    Krist, Pavel; Chvatil, David; Bila, Jiri

    2011-01-01

    This paper presents the design of a mathematical model and its fast simulation developed for the setup of the control system of the MT25 microtron, which is a cyclic electron accelerator. This type of accelerator has been controlled manually until now. The mathematical model is based on calculations of the electron motion in the accelerating cavity and vacuum chamber. The simulation diagram was created using the Matlab-Simulink tools. (author)

  14. A fast large dynamic range shaping amplifier for particle detector front-end

    Rivetti, Angelo; Delaurenti, Paolo

    2007-01-01

    The paper describes a fast shaping amplifier with rail-to-rail output swing. The circuit is based on a CMOS operational amplifier with a class AB output stage. A baseline holder, incorporating a closed-loop unity gain buffer with slew rate limitation, performs the AC coupling with the preamplifier and guarantees a baseline shift smaller than 3 mV for unipolar output pulses of 3 V and 10 MHz rate

  15. Influence of dynamic material properties on the design criteria of containment structures for fast breeder reactors

    Albertini, C.; Montagnani, M.

    1978-01-01

    Effects of defects in materials, created by welding processes and irradiation, are examined taking into account the influence of strain-rate. Materials examined are austenitic stainless steels, such as AISI 316 L and H, AISI 304 L. The influence of such parameters on the flow curves of these materials requires the introduction of additional safety coefficients in calculating the response of dynamically loaded structures such as the pressure vessel in the case of an accident. Furthermore the effects of dynamic multi-axial loading and wave propagation should be taken into account in the safety analysis. Running experiments in dynamic biaxial loading conditions are introduced. (author)

  16. Radiation assisted thermonuclear burn wave dynamics in heavy ion fast ignition of cylindrical deuterium-tritium fuel target

    Rehman, S.; Kouser, R.; Nazir, R.; Manzoor, Z.; Tasneem, G.; Jehan, N.; Nasim, M.H.; Salahuddin, M.

    2015-01-01

    Dynamics of thermonuclear burn wave propagation assisted by thermal radiation precursor in a heavy ion fast ignition of cylindrical deuterium-tritium (DT) fuel target are studied by two dimensional radiation hydrodynamic simulations using Multi-2D code. Thermal radiations, as they propagate ahead of the burn wave, suffer multiple reflections and preheat the fuel, are found to play a vital role in burn wave dynamics. After fuel ignition, the burn wave propagates in a steady state manner for some time. Multiple reflection and absorption of radiation at the fuel-tamper interface, fuel ablation and radial implosion driven by ablative shock and fast fusion rates on the fuel axis, at relatively later times, result into filamentary wave front. Strong pressure gradients are developed and sausage like structures behind the front are appeared. The situation leads to relatively reduced and non-uniform radial fuel burning and burn wave propagation. The fuel burning due to DD reaction is also taken into account and overall fusion energy and fusion power density, due to DT and DD reactions, during the burn wave propagation are determined as a function of time. (authors)

  17. Development and testing of a fast Fourier transform high dynamic-range spectral diagnostics for millimeter wave characterization

    Thoen, D. J.; Bongers, W. A.; Westerhof, E.; Baar, M. R. de; Berg, M. A. van den; Beveren, V. van; Goede, A. P. H.; Graswinckel, M. F.; Schueller, F. C.; Oosterbeek, J. W.; Buerger, A.; Hennen, B. A.

    2009-01-01

    A fast Fourier transform (FFT) based wide range millimeter wave diagnostics for spectral characterization of scattered millimeter waves in plasmas has been successfully brought into operation. The scattered millimeter waves are heterodyne downconverted and directly digitized using a fast analog-digital converter and a compact peripheral component interconnect computer. Frequency spectra are obtained by FFT in the time domain of the intermediate frequency signal. The scattered millimeter waves are generated during high power electron cyclotron resonance heating experiments on the TEXTOR tokamak and demonstrate the performance of the diagnostics and, in particular, the usability of direct digitizing and Fourier transformation of millimeter wave signals. The diagnostics is able to acquire 4 GHz wide spectra of signals in the range of 136-140 GHz. The rate of spectra is tunable and has been tested between 200 000 spectra/s with a frequency resolution of 100 MHz and 120 spectra/s with a frequency resolution of 25 kHz. The respective dynamic ranges are 52 and 88 dB. Major benefits of the new diagnostics are a tunable time and frequency resolution due to postdetection, near-real time processing of the acquired data. This diagnostics has a wider application in astrophysics, earth observation, plasma physics, and molecular spectroscopy for the detection and analysis of millimeter wave radiation, providing high-resolution spectra at high temporal resolution and large dynamic range.

  18. Impedance spectroscopy applied to the fast wounding dynamics of an electrical wound-healing assay in mammalian cells

    Bellotti, Mariela I.; Giana, Fabián E.; Bonetto, Fabián J.

    2015-08-01

    Electrical wound-healing assays are often used as a means to study in vitro cell migration and proliferation. In such analysis, a cell monolayer that sits on a small electrode is electrically wounded and its spectral impedance is then continuously measured in order to monitor the healing process. The relatively slow dynamics of the cell healing have been extensively studied, while those of the much faster wounding phase have not yet been investigated. An analysis of the electrical properties of a particular cell type during this phase could give extra information about the changes in the cell membrane due to the application of the wounding current, and could also be useful to optimize the wounding regime for different cell types. The main issue when trying to register information about these dynamics is that the traditional measurement scheme employed in typical wound-healing assays doesn’t allow the simultaneous application of the wounding signal and measurement of the system’s impedance. In this paper, we overcome this limitation by implementing a measurement strategy consisting of cycles of fast alternating low- and high-voltage signals applied on electrodes covered with mammalian cells. This approach is capable of registering the fast impedance changes during the transient regime corresponding to the cell wounding process. Furthermore, these quasi-simultaneous high- and low-voltage measurements can be compared in order to obtain an empirical correlation between both quantities.

  19. Impedance spectroscopy applied to the fast wounding dynamics of an electrical wound-healing assay in mammalian cells

    Bellotti, Mariela I; Giana, Fabián E; Bonetto, Fabián J

    2015-01-01

    Electrical wound-healing assays are often used as a means to study in vitro cell migration and proliferation. In such analysis, a cell monolayer that sits on a small electrode is electrically wounded and its spectral impedance is then continuously measured in order to monitor the healing process. The relatively slow dynamics of the cell healing have been extensively studied, while those of the much faster wounding phase have not yet been investigated. An analysis of the electrical properties of a particular cell type during this phase could give extra information about the changes in the cell membrane due to the application of the wounding current, and could also be useful to optimize the wounding regime for different cell types. The main issue when trying to register information about these dynamics is that the traditional measurement scheme employed in typical wound-healing assays doesn’t allow the simultaneous application of the wounding signal and measurement of the system’s impedance. In this paper, we overcome this limitation by implementing a measurement strategy consisting of cycles of fast alternating low- and high-voltage signals applied on electrodes covered with mammalian cells. This approach is capable of registering the fast impedance changes during the transient regime corresponding to the cell wounding process. Furthermore, these quasi-simultaneous high- and low-voltage measurements can be compared in order to obtain an empirical correlation between both quantities. (paper)

  20. Validity of the top-down approach of inverse dynamics analysis in fast and large rotational trunk movements.

    Iino, Yoichi; Kojima, Takeji

    2012-08-01

    This study investigated the validity of the top-down approach of inverse dynamics analysis in fast and large rotational movements of the trunk about three orthogonal axes of the pelvis for nine male collegiate students. The maximum angles of the upper trunk relative to the pelvis were approximately 47°, 49°, 32°, and 55° for lateral bending, flexion, extension, and axial rotation, respectively, with maximum angular velocities of 209°/s, 201°/s, 145°/s, and 288°/s, respectively. The pelvic moments about the axes during the movements were determined using the top-down and bottom-up approaches of inverse dynamics and compared between the two approaches. Three body segment inertial parameter sets were estimated using anthropometric data sets (Ae et al., Biomechanism 11, 1992; De Leva, J Biomech, 1996; Dumas et al., J Biomech, 2007). The root-mean-square errors of the moments and the absolute errors of the peaks of the moments were generally smaller than 10 N·m. The results suggest that the pelvic moment in motions involving fast and large trunk movements can be determined with a certain level of validity using the top-down approach in which the trunk is modeled as two or three rigid-link segments.

  1. Salmonella Intracellular Lifestyles and Their Impact on Host-to-Host Transmission.

    Pucciarelli, M Graciela; García-Del Portillo, Francisco

    2017-07-01

    More than a century ago, infections by Salmonella were already associated with foodborne enteric diseases with high morbidity in humans and cattle. Intestinal inflammation and diarrhea are hallmarks of infections caused by nontyphoidal Salmonella serovars, and these pathologies facilitate pathogen transmission to the environment. In those early times, physicians and microbiologists also realized that typhoid and paratyphoid fever caused by some Salmonella serovars could be transmitted by "carriers," individuals outwardly healthy or at most suffering from some minor chronic complaint. In his pioneering study of the nontyphoidal serovar Typhimurium in 1967, Takeuchi published the first images of intracellular bacteria enclosed by membrane-bound vacuoles in the initial stages of the intestinal epithelium penetration. These compartments, called Salmonella -containing vacuoles, are highly dynamic phagosomes with differing biogenesis depending on the host cell type. Single-cell studies involving real-time imaging and gene expression profiling, together with new approaches based on genetic reporters sensitive to growth rate, have uncovered unprecedented heterogeneous responses in intracellular bacteria. Subpopulations of intracellular bacteria displaying fast, reduced, or no growth, as well as cytosolic and intravacuolar bacteria, have been reported in both in vitro and in vivo infection models. Recent investigations, most of them focused on the serovar Typhimurium, point to the selection of persisting bacteria inside macrophages or following an autophagy attack in fibroblasts. Here, we discuss these heterogeneous intracellular lifestyles and speculate on how these disparate behaviors may impact host-to-host transmissibility of Salmonella serovars.

  2. An Improved Fast Flocking Algorithm with Obstacle Avoidance for Multiagent Dynamic Systems

    Jialiang Wang

    2014-01-01

    Full Text Available Flocking behavior is a common phenomenon in nature, such as flocks of birds and groups of fish. In order to make the agents effectively avoid obstacles and fast form flocking towards the direction of destination point, this paper proposes a fast multiagent obstacle avoidance (FMOA algorithm. FMOA is illustrated based on the status of whether the flocking has formed. If flocking has not formed, agents should avoid the obstacles toward the direction of target. If otherwise, these agents have reached the state of lattice and then these agents only need to avoid the obstacles and ignore the direction of target. The experimental results show that the proposed FMOA algorithm has better performance in terms of flocking path length. Furthermore, the proposed FMOA algorithm is applied to the formation flying of quad-rotor helicopters. Compared with other technologies to perform the localization of quad-rotor helicopter, this paper innovatively constructs a smart environment by deploying some wireless sensor network (WSN nodes using the proposed localization algorithm. Finally, the proposed FMOA algorithm is used to conduct the formation flying of these quad-rotor helicopters in the smart environment.

  3. The relationship between gallbladder dynamics and the migrating motor complex in fasting healthy subjects

    Qvist, N; Oster-Jørgensen, E; Rasmussen, L

    1988-01-01

    The relationship between gallbladder dynamics and the interdigestive migrating motor complex (MMC) was investigated in 10 healthy male volunteers by a hepatobiliary scintigraphy and gastroduodenal pressure recordings. Filling of the gallbladder commenced in late phase II or in phase III of the MM...

  4. Fast-scan em with digital image processing for dynamic experiments

    Charles W. McMillin; Fred C. Billingsley; Robert E. Frazer

    1973-01-01

    The recent introduction of accessory instrumentation capable of display at television scan rates suggests a broadened application for the scanning electron microscope - the direct observation of motion (dynamic events) at magnifactions otherwise unattainable. In one illustrative experiment, the transverse surface of southern pine was observed when subjected to large...

  5. Plasma dynamics study by fast imaging and Sm1-xNdxNiO3 thin film deposition

    Lafane, S.; Kerdja, T.; Abdelli-Messaci, S.; Malek, S.; Maaza, M.

    2009-01-01

    The plume expansion dynamics of an ablated target of Sm 2 O 3 , Nd 2 O 3 and NiO mixture oxides by KrF laser into 0.2 mbar oxygen atmosphere has been investigated using fast imaging. The study was carried out for two different laser fluences 2 and 3 J cm -2 . It was found that at early time delays, the expansion is still linear, independently of the laser fluence. However, as time evolves, the plume is decelerated and comes to rest. The plasma plume dynamics was analysed in the framework of Predtechensky and Mayorov model and drag model. It was found that Predtechensky and Mayorov model gives a general description of the plume expansion. However, at later time delays, it is rather the drag model which is valid. Furthermore, under the same conditions of pressure and fluences used for the plasma study, thin films were deposited at 4 cm from target surface and at temperature of 500 deg. C on (1 0 0) silicon substrates. The obtained layers were characterized by atomic force microscopy and electron dispersive X-ray spectroscopy diagnostics. A correlation between the films properties and the plasma plume dynamics was found.

  6. Model validation of solar PV plant with hybrid data dynamic simulation based on fast-responding generator method

    Zhao Dawei

    2016-01-01

    Full Text Available In recent years, a significant number of large-scale solar photovoltaic (PV plants have been put into operation or been under planning around the world. The model accuracy of solar PV plant is the key factor to investigate the mutual influences between solar PV plants and a power grid. However, this problem has not been well solved, especially in how to apply the real measurements to validate the models of the solar PV plants. Taking fast-responding generator method as an example, this paper presents a model validation methodology for solar PV plant via the hybrid data dynamic simulation. First, the implementation scheme of hybrid data dynamic simulation suitable for DIgSILENT PowerFactory software is proposed, and then an analysis model of solar PV plant integration based on IEEE 9 system is established. At last, model validation of solar PV plant is achieved by employing hybrid data dynamic simulation. The results illustrate the effectiveness of the proposed method in solar PV plant model validation.

  7. Dynamic studies of cardiac valvular disease using a new fast multiphase MR imaging technique

    Pettigrew, R.; Churchwell, A.; Parks, W.J.; Dannels, W.; Smith, H. III; Baron, M.G.

    1986-01-01

    To determine the potential utility of fast multiphase (FM) imaging for the assessment of cardiac valvular disease, ten healthy volunteers and 18 patients were studied. The FM technique employed gradient echoes with TE -- 15 msec and small exitation angles with TR -- 50 msec. Cine display of the electrocardiographically gated FM images allowed clear visualization of regurgitant blood flow in each of 15 patients with tricuspid or mitral insufficiency. Magnetic field distortions in two patients with Bjork-Shiley aortic prostheses and regurgitation prevented definitive visualization of the flow patterns. An equivocal flow pattern was seen in one case of mitral stenosis. Thus, FM imaging may have significant utility as an adjunctive procedure for the assessment of atrioventricular valve insufficiently, without requiring a contrast agent. Difficulties may exist with some prosthetic valves

  8. Neutron spectroscopy measurements and modeling of neutral beam heating fast ion dynamics

    Hellesen, C; Sunden, E Andersson; Conroy, S; Ericsson, G; Johnson, M Gatu; Hjalmarsson, A; Kaellne, J; Ronchi, E; Sjoestrand, H; Weiszflog, M; Albergante, M; Ballabio, L; Gorini, G; Tardocchi, M; Giacomelli, L; Jenkins, I; Voitsekhovitch, I

    2010-01-01

    The energy spectrum of the neutron emission from beam-target reactions in fusion plasmas at the Joint European Torus (JET) has been investigated. Different beam energies as well as injection angles were used. Both measurements and simulations of the energy spectrum were done. The measurements were made with the time-of-flight spectrometer TOFOR. Simulations of the neutron spectrum were based on first-principle calculations of neutral beam deposition profiles and the fast ion slowing down in the plasma using the code NUBEAM, which is a module of the TRANSP package. The shape of the neutron energy spectrum was seen to vary significantly depending on the energy of the beams as well as the injection angle and the deposition profile in the plasma. Cross validations of the measured and modeled neutron energy spectra were made, showing a good agreement for all investigated scenarios.

  9. Fast nanoscale addressability of nitrogen-vacancy spins via coupling to a dynamic ferromagnetic vortex

    Wolf, M. S.; Badea, R.; Berezovsky, J.

    2016-01-01

    The core of a ferromagnetic vortex domain creates a strong, localized magnetic field, which can be manipulated on nanosecond timescales, providing a platform for addressing and controlling individual nitrogen-vacancy centre spins in diamond at room temperature, with nanometre-scale resolution. Here, we show that the ferromagnetic vortex can be driven into proximity with a nitrogen-vacancy defect using small applied magnetic fields, inducing significant nitrogen-vacancy spin splitting. We also find that the magnetic field gradient produced by the vortex is sufficient to address spins separated by nanometre-length scales. By applying a microwave-frequency magnetic field, we drive both the vortex and the nitrogen-vacancy spins, resulting in enhanced coherent rotation of the spin state. Finally, we demonstrate that by driving the vortex on fast timescales, sequential addressing and coherent manipulation of spins is possible on ∼100 ns timescales. PMID:27296550

  10. Fast electrons from multi-electron dynamics in xenon clusters induced by inner-shell ionization

    Bostedt, Christoph; Thomas, Heiko; Hoener, Matthias; Moeller, Thomas; Saalmann, Ulf; Georgescu, Ionut; Gnodtke, Christian; Rost, Jan-Michael

    2010-01-01

    Fast electrons emitted from xenon clusters in strong femtosecond 90 eV pulses have been measured at the Free-electron Laser in Hamburg (FLASH). Energy absorption occurs mainly through atomic inner-shell photo-ionization. Photo-electrons are trapped in the strong Coulomb potential of the cluster ions and form a non-equilibrium plasma with supra-atomic density. Its equilibration through multiple energy-exchanging collisions within the entire cluster volume produces electrons with energies well beyond the dominant emission line of atomic xenon. Here, in contrast to traditional low-frequency laser plasma heating, the plasma gains energy from electrons delivered through massive single-photon excitation from bound states. Electron emission induced by thermalization of a non-equilibrium plasma is expected to be a general phenomenon occurring for strong atomic x-ray absorption in extended systems.

  11. Discontinuity in Fast Dynamics at the Glass Transition of ortho-Terphenyl.

    Hoffman, David J; Fayer, Michael D

    2017-11-16

    The dynamics of the molecular glass former ortho-terphenyl through the glass transition were observed with two-dimensional infrared vibrational spectroscopy measurements of spectral diffusion using the small probe molecule phenylselenocyanate. Although the slow diffusive motions were not visible on the experimental time scale, a picosecond-scale exponential relaxation was observed at temperatures from above to well below the glass transition temperature. The characteristic time scale has a smooth temperature dependence from the liquid into the glass phase, but the range of vibrational frequencies the probe samples displayed a discontinuity at the glass transition temperature. Complementary pump-probe experiments associate the observed motion with density fluctuations. The key features of the dynamics are reproduced with a simple corrugated well potential energy surface model. In addition, the temperature dependence of the homogeneous vibrational dephasing was found to have a T 2 functional form, where T is the absolute temperature.

  12. Fast Virtual Fractional Flow Reserve Based Upon Steady-State Computational Fluid Dynamics Analysis

    Paul D. Morris, PhD

    2017-08-01

    Full Text Available Fractional flow reserve (FFR-guided percutaneous intervention is superior to standard assessment but remains underused. The authors have developed a novel “pseudotransient” analysis protocol for computing virtual fractional flow reserve (vFFR based upon angiographic images and steady-state computational fluid dynamics. This protocol generates vFFR results in 189 s (cf >24 h for transient analysis using a desktop PC, with <1% error relative to that of full-transient computational fluid dynamics analysis. Sensitivity analysis demonstrated that physiological lesion significance was influenced less by coronary or lesion anatomy (33% and more by microvascular physiology (59%. If coronary microvascular resistance can be estimated, vFFR can be accurately computed in less time than it takes to make invasive measurements.

  13. Adiabatic fast passage application in solid state NMR study of cross relaxation and molecular dynamics in heteronuclear systems.

    Baranowski, M; Woźniak-Braszak, A; Jurga, K

    2016-01-01

    The paper presents the benefits of using fast adiabatic passage for the study of molecular dynamics in the solid state heteronuclear systems in the laboratory frame. A homemade pulse spectrometer operating at the frequency of 30.2MHz and 28.411MHz for protons and fluorines, respectively, has been enhanced with microcontroller direct digital synthesizer DDS controller [1-4]. This work briefly describes how to construct a low-cost and easy-to-assemble adiabatic extension set for homemade and commercial spectrometers based on recently very popular Arduino shields. The described set was designed for fast adiabatic generation. Timing and synchronization problems are discussed. The cross-relaxation experiments with different initial states of the two spin systems have been performed. Contrary to our previous work [5] where the steady-state NOE experiments were conducted now proton spins (1)H are polarized in the magnetic field B0 while fluorine spins (19)F are perturbed by selective saturation for a short time and then the system is allowed to evolve for a period in the absence of a saturating field. The adiabatic passage application leads to a reversal of magnetization of fluorine spins and increases the amplitude of the signal. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Higgs Discovery: Impact on Composite Dynamics Technicolor & eXtreme Compositeness Thinking Fast and Slow

    Sannino, Francesco

    I discuss the impact of the discovery of a Higgs-like state on composite dynamics starting by critically examining the reasons in favour of either an elementary or composite nature of this state. Accepting the standard model interpretation I re-address the standard model vacuum stability within a Weyl-consistent computation. I will carefully examine the fundamental reasons why what has been discovered might not be the standard model Higgs. Dynamical electroweak breaking naturally addresses a number of the fundamental issues unsolved by the standard model interpretation. However this paradigm has been challenged by the discovery of a not-so-heavy Higgs-like state. I will therefore review the recent discovery1 that the standard model top-induced radiative corrections naturally reduce the intrinsic non-perturbative mass of the composite Higgs state towards the desired experimental value. Not only we have a natural and testable working framework but we have also suggested specic gauge theories that can realise, at the fundamental level, these minimal models of dynamical electroweak symmetry breaking. These strongly coupled gauge theories are now being heavily investigated via first principle lattice simulations with encouraging results. The new findings show that the recent naive claims made about new strong dynamics at the electroweak scale being disfavoured by the discovery of a not-so-heavy composite Higgs are unwarranted. I will then introduce the more speculative idea of extreme compositeness according to which not only the Higgs sector of the standard model is composite but also quarks and leptons, and provide a toy example in the form of gauge-gauge duality.

  15. An adaptive immune optimization algorithm with dynamic lattice searching operation for fast optimization of atomic clusters

    Wu, Xia; Wu, Genhua

    2014-01-01

    Highlights: • A high efficient method for optimization of atomic clusters is developed. • Its performance is studied by optimizing Lennard-Jones clusters and Ag clusters. • The method is proved to be quite efficient. • A new Ag 61 cluster with stacking-fault face-centered cubic motif is found. - Abstract: Geometrical optimization of atomic clusters is performed by a development of adaptive immune optimization algorithm (AIOA) with dynamic lattice searching (DLS) operation (AIOA-DLS method). By a cycle of construction and searching of the dynamic lattice (DL), DLS algorithm rapidly makes the clusters more regular and greatly reduces the potential energy. DLS can thus be used as an operation acting on the new individuals after mutation operation in AIOA to improve the performance of the AIOA. The AIOA-DLS method combines the merit of evolutionary algorithm and idea of dynamic lattice. The performance of the proposed method is investigated in the optimization of Lennard-Jones clusters within 250 atoms and silver clusters described by many-body Gupta potential within 150 atoms. Results reported in the literature are reproduced, and the motif of Ag 61 cluster is found to be stacking-fault face-centered cubic, whose energy is lower than that of previously obtained icosahedron

  16. Fast generation of 4D PET-MR data from real dynamic MR acquisitions

    Tsoumpas, C; Buerger, C; King, A P; Schleyer, P; Schaeffter, T; Marsden, P K; Mollet, P; Keereman, V; Vandenberghe, S; Schulz, V

    2011-01-01

    We have implemented and evaluated a framework for simulating simultaneous dynamic PET-MR data using the anatomic and dynamic information from real MR acquisitions. PET radiotracer distribution is simulated by assigning typical FDG uptake values to segmented MR images with manually inserted additional virtual lesions. PET projection data and images are simulated using analytic forward projections (including attenuation and Poisson statistics) implemented within the image reconstruction package STIR. PET image reconstructions are also performed with STIR. The simulation is validated with numerical simulation based on Monte Carlo (GATE) which uses more accurate physical modelling, but has 150x slower computation time compared to the analytic method for ten respiratory positions and is 7000x slower when performing multiple realizations. Results are validated in terms of region of interest mean values and coefficients of variation for 65 million coincidences including scattered events. Although some discrepancy is observed, agreement between the two different simulation methods is good given the statistical noise in the data. In particular, the percentage difference of the mean values is 3.1% for tissue, 17% for the lungs and 18% for a small lesion. The utility of the procedure is demonstrated by simulating realistic PET-MR datasets from multiple volunteers with different breathing patterns. The usefulness of the toolkit will be shown for performance investigations of the reconstruction, motion correction and attenuation correction algorithms for dynamic PET-MR data.

  17. Differentiation between benign and malignant colon tumors using fast dynamic gadolinium-enhanced MR colonography; a feasibility study

    Achiam, M.P., E-mail: achiam1@dadlnet.d [Department of Diagnostic Radiology, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Surgical Gastroenterology D, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark); Andersen, L.P.H.; Klein, M. [Department of Surgical Gastroenterology D, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark); Logager, V.; Chabanova, E.; Thomsen, H.S. [Department of Diagnostic Radiology, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark); Rosenberg, J. [Department of Surgical Gastroenterology D, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark)

    2010-06-15

    Background: Colorectal cancer will present itself as a bowel obstruction in 16-23% of all cases. However, not all obstructing tumors are malignant and the differentiation between a benign and a malignant tumor can be difficult. The purpose of our study was to determine whether fast dynamic gadolinium-enhanced MR imaging combined with MR colonography could be used to differentiate a benign from a malignant obstructing colon tumor. Methods: Patients with benign colon tumor stenosis, based on diverticulitis, were asked to participate in the study. The same number of patients with verified colorectal cancer was included. Both groups had to be scheduled for surgery to be included. Two blinded observers analyzed the tumors on MR by placing a region of interest in the tumor and a series of parameters were evaluated, e.g. wash-in, wash-out and time-to-peak. Results: 14 patients were included. The wash-in and wash-out rates were significantly different between the benign and malignant tumors, and a clear distinction between benign and malignant disease was therefore possible by looking only at the MR data. Furthermore, MR colography evaluating the rest of the colon past the stenosis was possible with all patients. Conclusion: The results showed the feasibility of using fast dynamic gadolinium-enhanced MR imaging to differentiate between benign and malignant colonic tumors. With a high intra-class correlation and significant differences found on independent segments of the tumor, the method appears to be reproducible. Furthermore, the potential is big in performing a full preoperative colon evaluation even in patients with obstructing cancer. Trial number: (NCT00114829).

  18. Differentiation between benign and malignant colon tumors using fast dynamic gadolinium-enhanced MR colonography; a feasibility study

    Achiam, M.P.; Andersen, L.P.H.; Klein, M.; Logager, V.; Chabanova, E.; Thomsen, H.S.; Rosenberg, J.

    2010-01-01

    Background: Colorectal cancer will present itself as a bowel obstruction in 16-23% of all cases. However, not all obstructing tumors are malignant and the differentiation between a benign and a malignant tumor can be difficult. The purpose of our study was to determine whether fast dynamic gadolinium-enhanced MR imaging combined with MR colonography could be used to differentiate a benign from a malignant obstructing colon tumor. Methods: Patients with benign colon tumor stenosis, based on diverticulitis, were asked to participate in the study. The same number of patients with verified colorectal cancer was included. Both groups had to be scheduled for surgery to be included. Two blinded observers analyzed the tumors on MR by placing a region of interest in the tumor and a series of parameters were evaluated, e.g. wash-in, wash-out and time-to-peak. Results: 14 patients were included. The wash-in and wash-out rates were significantly different between the benign and malignant tumors, and a clear distinction between benign and malignant disease was therefore possible by looking only at the MR data. Furthermore, MR colography evaluating the rest of the colon past the stenosis was possible with all patients. Conclusion: The results showed the feasibility of using fast dynamic gadolinium-enhanced MR imaging to differentiate between benign and malignant colonic tumors. With a high intra-class correlation and significant differences found on independent segments of the tumor, the method appears to be reproducible. Furthermore, the potential is big in performing a full preoperative colon evaluation even in patients with obstructing cancer. Trial number: (NCT00114829).

  19. Dynamic grazing incidence fast atom diffraction during molecular beam epitaxial growth of GaAs

    Atkinson, P., E-mail: atkinson@insp.jussieu.fr; Eddrief, M. [Sorbonne Universités, UPMC Univ. Paris 06, UMR 7588, INSP, F-75005 Paris (France); CNRS, UMR 7588, Institut des NanoSciences de Paris, 4 place Jussieu, F-75005 Paris (France); Etgens, V. H. [CNRS, UMR 7588, Institut des NanoSciences de Paris, 4 place Jussieu, F-75005 Paris (France); VeDeCom-Université Versailles Saint-Quentin en Yvelines, Versailles (France); Khemliche, H., E-mail: hocine.khemliche@u-psud.fr; Debiossac, M.; Mulier, M.; Lalmi, B.; Roncin, P. [ISMO UMR8214 CNRS-Université Paris-Sud, Orsay F-91400 (France); Momeni, A. [ISMO UMR8214 CNRS-Université Paris-Sud, Orsay F-91400 (France); Univ. Cergy Pontoise, F-95031 Cergy (France)

    2014-07-14

    A Grazing Incidence Fast Atom Diffraction (GIFAD) system has been mounted on a commercial molecular beam epitaxy chamber and used to monitor GaAs growth in real-time. In contrast to the conventionally used Reflection High Energy Electron Diffraction, all the GIFAD diffraction orders oscillate in phase, with the change in intensity related to diffuse scattering at step edges. We show that the scattered intensity integrated over the Laue circle is a robust method to monitor the periodic change in surface roughness during layer-by-layer growth, with oscillation phase and amplitude independent of incidence angle and crystal orientation. When there is a change in surface reconstruction at the start of growth, GIFAD intensity oscillations show that there is a corresponding delay in the onset of layer-by-layer growth. In addition, changes in the relative intensity of different diffraction orders have been observed during growth showing that GIFAD has the potential to provide insight into the preferential adatom attachment sites on the surface reconstruction during growth.

  20. Design features affecting dynamic behaviour of fast reactor cores. Overview paper

    Kayser, G.; Gouriou, A.

    1982-01-01

    The study of dynamic response of a LMFBR to normal and accidental transients needs first of all a simulation code taking into account all the important effects. The DYN-1 code aims at this target. It represents with a sufficiently accurate meshing the core in a 2D geometry for the thermal and reactivity effects, while the kinetics of this core are calculated with a point model. The primary pool, secondary loops, steam generator are also represented, as well as the control and protective systems. A schematic representation of this code applied to Super Phenix 1 is shown. Simpler codes are sometimes good enough for parametric studies. The dynamic studies of this plant are related to different situations which can be classified in the following groups: normal operation, the stability of the reactor in a steady state situation, or with power or frequency regulation; the normal transients from one power level to another (startup procedures); the incidental situations, with the protective shut-down systems operative (for instance loss of electric supply power); the hypothetical accidental situations without scram. The first three groups of problems arise necessarily in the study of each plant ; the last group is related to very hypothetical situations, the probability of which can be made very low by a high reliability of the shut-down system. Also the need to study them depends on this reliability and subsequently on the philosophy which the licensing authorities adopt

  1. Fast optimization of binary clusters using a novel dynamic lattice searching method

    Wu, Xia; Cheng, Wen

    2014-01-01

    Global optimization of binary clusters has been a difficult task despite of much effort and many efficient methods. Directing toward two types of elements (i.e., homotop problem) in binary clusters, two classes of virtual dynamic lattices are constructed and a modified dynamic lattice searching (DLS) method, i.e., binary DLS (BDLS) method, is developed. However, it was found that the BDLS can only be utilized for the optimization of binary clusters with small sizes because homotop problem is hard to be solved without atomic exchange operation. Therefore, the iterated local search (ILS) method is adopted to solve homotop problem and an efficient method based on the BDLS method and ILS, named as BDLS-ILS, is presented for global optimization of binary clusters. In order to assess the efficiency of the proposed method, binary Lennard-Jones clusters with up to 100 atoms are investigated. Results show that the method is proved to be efficient. Furthermore, the BDLS-ILS method is also adopted to study the geometrical structures of (AuPd) 79 clusters with DFT-fit parameters of Gupta potential

  2. Design of Neural Networks for Fast Convergence and Accuracy: Dynamics and Control

    Maghami, Peiman G.; Sparks, Dean W., Jr.

    1997-01-01

    A procedure for the design and training of artificial neural networks, used for rapid and efficient controls and dynamics design and analysis for flexible space systems, has been developed. Artificial neural networks are employed, such that once properly trained, they provide a means of evaluating the impact of design changes rapidly. Specifically, two-layer feedforward neural networks are designed to approximate the functional relationship between the component/spacecraft design changes and measures of its performance or nonlinear dynamics of the system/components. A training algorithm, based on statistical sampling theory, is presented, which guarantees that the trained networks provide a designer-specified degree of accuracy in mapping the functional relationship. Within each iteration of this statistical-based algorithm, a sequential design algorithm is used for the design and training of the feedforward network to provide rapid convergence to the network goals. Here, at each sequence a new network is trained to minimize the error of previous network. The proposed method should work for applications wherein an arbitrary large source of training data can be generated. Two numerical examples are performed on a spacecraft application in order to demonstrate the feasibility of the proposed approach.

  3. A dynamic-biased dual-loop-feedback CMOS LDO regulator with fast transient response

    Wang Han; Sun Maomao

    2014-01-01

    This paper presents a low-dropout regulator (LDO) for portable applications with dual-loop feedback and a dynamic bias circuit. The dual-loop feedback structure is adopted to reduce the output voltage spike and the response time of the LDO. The dynamic bias circuit enhances the slew rate at the gate of the power transistor. In addition, an adaptive miller compensation technique is employed, from which a single pole system is realized and over a 59° phase margin is achieved under the full range of the load current. The proposed LDO has been implemented in a 0.6-μm CMOS process. From the experimental results, the regulator can operate with a minimum dropout voltage of 200 mV at a maximum 300 mA load and I Q of 113 μA. The line regulation and load regulation are improved to 0.1 mV/V and 3.4 μV/mA due to the sufficient loop gain provided by the dual feedback loops. Under a full range load current step, the voltage spikes and the recovery time of the proposed LDO is reduced to 97 mV and 0.142 μs respectively. (semiconductor integrated circuits)

  4. Ablation dynamics - from absorption to heat accumulation/ultra-fast laser matter interaction

    Kramer, Thorsten; Remund, Stefan; Jäggi, Beat; Schmid, Marc; Neuenschwander, Beat

    2018-05-01

    Ultra-short laser radiation is used in manifold industrial applications today. Although state-of-the-art laser sources are providing an average power of 10-100 W with repetition rates of up to several megahertz, most applications do not benefit from it. On the one hand, the processing speed is limited to some hundred millimeters per second by the dynamics of mechanical axes or galvanometric scanners. On the other hand, high repetition rates require consideration of new physical effects such as heat accumulation and shielding that might reduce the process efficiency. For ablation processes, process efficiency can be expressed by the specific removal rate, ablated volume per time, and average power. The analysis of the specific removal rate for different laser parameters, like average power, repetition rate or pulse duration, and process parameters, like scanning speed or material, can be used to find the best operation point for microprocessing applications. Analytical models and molecular dynamics simulations based on the so-called two-temperature model reveal the causes for the appearance of limiting physical effects. The findings of models and simulations can be used to take advantage and optimize processing strategies.

  5. AWE-WQ: fast-forwarding molecular dynamics using the accelerated weighted ensemble.

    Abdul-Wahid, Badi'; Feng, Haoyun; Rajan, Dinesh; Costaouec, Ronan; Darve, Eric; Thain, Douglas; Izaguirre, Jesús A

    2014-10-27

    A limitation of traditional molecular dynamics (MD) is that reaction rates are difficult to compute. This is due to the rarity of observing transitions between metastable states since high energy barriers trap the system in these states. Recently the weighted ensemble (WE) family of methods have emerged which can flexibly and efficiently sample conformational space without being trapped and allow calculation of unbiased rates. However, while WE can sample correctly and efficiently, a scalable implementation applicable to interesting biomolecular systems is not available. We provide here a GPLv2 implementation called AWE-WQ of a WE algorithm using the master/worker distributed computing WorkQueue (WQ) framework. AWE-WQ is scalable to thousands of nodes and supports dynamic allocation of computer resources, heterogeneous resource usage (such as central processing units (CPU) and graphical processing units (GPUs) concurrently), seamless heterogeneous cluster usage (i.e., campus grids and cloud providers), and support for arbitrary MD codes such as GROMACS, while ensuring that all statistics are unbiased. We applied AWE-WQ to a 34 residue protein which simulated 1.5 ms over 8 months with peak aggregate performance of 1000 ns/h. Comparison was done with a 200 μs simulation collected on a GPU over a similar timespan. The folding and unfolded rates were of comparable accuracy.

  6. Comparison of MRI fast SPGR single slice scan and continuous dynamic scan in patients with obstructive sleep apnea-hypopnea syndrome

    Zhang Xinyu [Department of Radiology, Medical School Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003 (China)], E-mail: myginny2@sina.com; Yang Xue [Department of Radiology, Medical School Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003 (China)], E-mail: yangxueqyfy@126.com; Hua Hui [Department of Otorhinolaryngology-Head and Neck Surgery, Medical School Hospital of Qingdao University, Qingdao (China)], E-mail: huahuisky@163.com; Chen Jingjing [Department of Radiology, Medical School Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003 (China)], E-mail: chenjingjingsky@126.com

    2009-07-15

    Objective: To evaluate the application value of MRI fast SPGR single slice scan in patients with obstructive sleep apnea-hypopnea syndrome when comparing the images between fast SPGR single slice scan and continuous dynamic scan. Methods: Eighteen patients with obstructive sleep apnea-hypopnea syndrome were examined by fast SPGR single slice scan and continuous dynamic scan in turn. Fast SPGR single slice scans were conducted when the phases of apnea, inspiration and expiration appeared on the respiratory wave of the subjects. Fast SPGR continuous dynamic scans were conducted when the patients were awake and apneic. The scan planes were median sagittal plane and axial planes (the slice of middle part of palate, the slice of inferior part of palate, the slice of middle part of lingual root and the slice of 0.5 cm beneath the free margin of epiglottis). The obstructed sites and the cross-sectional areas of upper airway were compared between the two scan methods. Results: Seven cases showed complete obstruction at the narrowest sites of upper airway when apnea appeared; eleven cases showed marked decrease in cross-sectional areas at the narrowest sites compared with the areas when the patients were awake; two cases manifested multiple narrowness. The obstructed sites showed by the two scan methods were same. The difference of the cross-sectional areas of upper airway between the two scan methods was insignificant (P > 0.05). Conclusion: Fast SPGR single slice scan can accurately reflect the obstructed sites of upper airway when the breath breaks off and is the complementary method of continuous dynamic scan. Sometimes, single slice scan can replace continuous dynamic scan.

  7. Fast, Highly-Sensitive, and Wide-Dynamic-Range Interdigitated Capacitor Glucose Biosensor Using Solvatochromic Dye-Containing Sensing Membrane.

    Khan, Md Rajibur Rahaman; Khalilian, Alireza; Kang, Shin-Won

    2016-02-20

    In this paper, we proposed an interdigitated capacitor (IDC)-based glucose biosensor to measure different concentrations of glucose from 1 μM to 1 M. We studied four different types of solvatochromic dyes: Auramine O, Nile red, Rhodamine B, and Reichardt's dye (R-dye). These dyes were individually incorporated into a polymer [polyvinyl chloride (PVC)] and N,N-Dimethylacetamide (DMAC) solution to make the respective dielectric/sensing materials. To the best of our knowledge, we report for the first time an IDC glucose biosensing system utilizing a solvatochromic-dye-containing sensing membrane. These four dielectric or sensing materials were individually placed into the interdigitated electrode (IDE) by spin coating to make four IDC glucose biosensing elements. The proposed IDC glucose biosensor has a high sensing ability over a wide dynamic range and its sensitivity was about 23.32 mV/decade. It also has fast response and recovery times of approximately 7 s and 5 s, respectively, excellent reproducibility with a standard deviation of approximately 0.023, highly stable sensing performance, and real-time monitoring capabilities. The proposed IDC glucose biosensor was compared with an IDC, potentiometric, FET, and fiber-optic glucose sensor with respect to response time, dynamic range width, sensitivity, and linearity. We observed that the designed IDC glucose biosensor offered excellent performance.

  8. A High-Speed Vision-Based Sensor for Dynamic Vibration Analysis Using Fast Motion Extraction Algorithms

    Dashan Zhang

    2016-04-01

    Full Text Available The development of image sensor and optics enables the application of vision-based techniques to the non-contact dynamic vibration analysis of large-scale structures. As an emerging technology, a vision-based approach allows for remote measuring and does not bring any additional mass to the measuring object compared with traditional contact measurements. In this study, a high-speed vision-based sensor system is developed to extract structure vibration signals in real time. A fast motion extraction algorithm is required for this system because the maximum sampling frequency of the charge-coupled device (CCD sensor can reach up to 1000 Hz. Two efficient subpixel level motion extraction algorithms, namely the modified Taylor approximation refinement algorithm and the localization refinement algorithm, are integrated into the proposed vision sensor. Quantitative analysis shows that both of the two modified algorithms are at least five times faster than conventional upsampled cross-correlation approaches and achieve satisfactory error performance. The practicability of the developed sensor is evaluated by an experiment in a laboratory environment and a field test. Experimental results indicate that the developed high-speed vision-based sensor system can extract accurate dynamic structure vibration signals by tracking either artificial targets or natural features.

  9. Fast, Highly-Sensitive, and Wide-Dynamic-Range Interdigitated Capacitor Glucose Biosensor Using Solvatochromic Dye-Containing Sensing Membrane

    Md. Rajibur Rahaman Khan

    2016-02-01

    Full Text Available In this paper, we proposed an interdigitated capacitor (IDC-based glucose biosensor to measure different concentrations of glucose from 1 μM to 1 M. We studied four different types of solvatochromic dyes: Auramine O, Nile red, Rhodamine B, and Reichardt’s dye (R-dye. These dyes were individually incorporated into a polymer [polyvinyl chloride (PVC] and N,N-Dimethylacetamide (DMAC solution to make the respective dielectric/sensing materials. To the best of our knowledge, we report for the first time an IDC glucose biosensing system utilizing a solvatochromic-dye-containing sensing membrane. These four dielectric or sensing materials were individually placed into the interdigitated electrode (IDE by spin coating to make four IDC glucose biosensing elements. The proposed IDC glucose biosensor has a high sensing ability over a wide dynamic range and its sensitivity was about 23.32 mV/decade. It also has fast response and recovery times of approximately 7 s and 5 s, respectively, excellent reproducibility with a standard deviation of approximately 0.023, highly stable sensing performance, and real-time monitoring capabilities. The proposed IDC glucose biosensor was compared with an IDC, potentiometric, FET, and fiber-optic glucose sensor with respect to response time, dynamic range width, sensitivity, and linearity. We observed that the designed IDC glucose biosensor offered excellent performance.

  10. Fast negative feedback enables mammalian auditory nerve fibers to encode a wide dynamic range of sound intensities.

    Mark Ospeck

    Full Text Available Mammalian auditory nerve fibers (ANF are remarkable for being able to encode a 40 dB, or hundred fold, range of sound pressure levels into their firing rate. Most of the fibers are very sensitive and raise their quiescent spike rate by a small amount for a faint sound at auditory threshold. Then as the sound intensity is increased, they slowly increase their spike rate, with some fibers going up as high as ∼300 Hz. In this way mammals are able to combine sensitivity and wide dynamic range. They are also able to discern sounds embedded within background noise. ANF receive efferent feedback, which suggests that the fibers are readjusted according to the background noise in order to maximize the information content of their auditory spike trains. Inner hair cells activate currents in the unmyelinated distal dendrites of ANF where sound intensity is rate-coded into action potentials. We model this spike generator compartment as an attenuator that employs fast negative feedback. Input current induces rapid and proportional leak currents. This way ANF are able to have a linear frequency to input current (f-I curve that has a wide dynamic range. The ANF spike generator remains very sensitive to threshold currents, but efferent feedback is able to lower its gain in response to noise.

  11. Studies on plant dynamics of sodium-cooled fast breeder reactors - verification of a plant model

    Schubert, B.

    1988-01-01

    For the analysis of sodium-cooled FBR safety and dynamics theoretical models are used, which have to be verified. In this report the verification of the plant model SSC-L is conducted by the comparison of calculated data with measurements of the experimental reactors KNK II and RAPSODIE. For this the plant model is extended and adapted. In general only small differences between calculated and measured data are recognized. The results are used to improve and complete the plant model. The extensions of the plant model applicability are used for the calculation of a loss of heat sink transient with reactor scram, considering pipes as passive heat sinks. (orig./HP) With 69 figs., 10 tabs [de

  12. Dynamic simulation of a sodium-cooled fast reactor power plant

    Shinaishin, M.A.M.

    1976-01-01

    Simulation of the dynamic behavior of the Clinch River Breeder Reactor Plant (CRBRP) is dealt with. The range of transients under consideration extends from a moderate transient, of the type referred to as Anticipated Transient Without Scram (ATWS), to a transient initiated by an unexpected accident followed by reactor scram. The moderate range of transients can be simulated by a digital simulator referred to as the CRBRP ATWS simulator. Two versions of this simulator were prepared; in one, the plant controllers were not included, whereas, in the other, the controllers were incorporated. In addition to the usual assumption of lumped parameters, uniform heat transfer and point kinetics (prompt jump) have been the main approximations in this and other simulators (see below). Two different transport-delay models have also been installed in all simulators. The simulators were constructed using the DARE-P System, developed by the Electrical Engineering Department at the University of Arizona

  13. Fast evaluation of protein dynamics from deficient 15N relaxation data

    Jaremko, Łukasz

    2018-03-28

    Simple and convenient method of protein dynamics evaluation from the insufficient experimental N relaxation data is presented basing on the ratios, products, and differences of longitudinal and transverse N relaxation rates obtained at a single magnetic field. Firstly, the proposed approach allows evaluating overall tumbling correlation time (nanosecond time scale). Next, local parameters of the model-free approach characterizing local mobility of backbone amide N–H vectors on two different time scales, S and R, can be elucidated. The generalized order parameter, S, describes motions on the time scale faster than the overall tumbling correlation time (pico- to nanoseconds), while the chemical exchange term, R, identifies processes slower than the overall tumbling correlation time (micro- to milliseconds). Advantages and disadvantages of different methods of data handling are thoroughly discussed.

  14. Complex dynamics in a food chain with slow and fast processes

    Jiang Yongxin; Yang Jianping

    2009-01-01

    This paper is devoted to the analysis of the dynamic behavior of a three-species food chain model, in which two predators compete for the same prey while one of the predators feeds on the other. Under the assumption that the time responses of the three trophic levels are extremely diversified, the model is proved to have homoclinic orbit. We firstly use geometric singular perturbation method to detect singular homoclinic orbits as well as parameter combinations for which these orbits exist. Then, we show, numerically, that there exist also nonsingular homoclinic orbits that tend toward the singular ones for slightly different parameter values. This analysis is particularly helpful to understanding the chaotic behavior of the food chains.

  15. Fast pairwise structural RNA alignments by pruning of the dynamical programming matrix

    Havgaard, Jakob Hull; Torarinsson, Elfar; Gorodkin, Jan

    2007-01-01

    and backtracked in a normal fashion. Finally, the FOLDALIGN algorithm has also been updated with a better memory implementation and an improved energy model. With these improvements in the algorithm, the FOLDALIGN software package provides the molecular biologist with an efficient and user-friendly tool...... the advantage of providing the constraints dynamically. This has been included in a new implementation of the FOLDALIGN algorithm for pairwise local or global structural alignment of RNA sequences. It is shown that time and memory requirements are dramatically lowered while overall performance is maintained....... Furthermore, a new divide and conquer method is introduced to limit the memory requirement during global alignment and backtrack of local alignment. All branch points in the computed RNA structure are found and used to divide the structure into smaller unbranched segments. Each segment is then realigned...

  16. Fast plane wave density functional theory molecular dynamics calculations on multi-GPU machines

    Jia, Weile; Fu, Jiyun; Cao, Zongyan; Wang, Long; Chi, Xuebin; Gao, Weiguo; Wang, Lin-Wang

    2013-01-01

    Plane wave pseudopotential (PWP) density functional theory (DFT) calculation is the most widely used method for material simulations, but its absolute speed stagnated due to the inability to use large scale CPU based computers. By a drastic redesign of the algorithm, and moving all the major computation parts into GPU, we have reached a speed of 12 s per molecular dynamics (MD) step for a 512 atom system using 256 GPU cards. This is about 20 times faster than the CPU version of the code regardless of the number of CPU cores used. Our tests and analysis on different GPU platforms and configurations shed lights on the optimal GPU deployments for PWP-DFT calculations. An 1800 step MD simulation is used to study the liquid phase properties of GaInP

  17. Communication: Fast dynamics perspective on the breakdown of the Stokes-Einstein law in fragile glassformers.

    Puosi, F; Pasturel, A; Jakse, N; Leporini, D

    2018-04-07

    The breakdown of the Stokes-Einstein (SE) law in fragile glassformers is examined by Molecular-Dynamics simulations of atomic liquids and polymers and consideration of the experimental data concerning the archetypical ortho-terphenyl glassformer. All the four systems comply with the universal scaling between the viscosity (or the structural relaxation) and the Debye-Waller factor ⟨u 2 ⟩, the mean square amplitude of the particle rattling in the cage formed by the surrounding neighbors. It is found that the SE breakdown is scaled in a master curve by a reduced ⟨u 2 ⟩. Two approximated expressions of the latter, with no and one adjustable parameter, respectively, are derived.

  18. Fast evaluation of protein dynamics from deficient 15N relaxation data

    Jaremko, Łukasz; Jaremko, Mariusz; Ejchart, Andrzej; Nowakowski, Michał

    2018-01-01

    Simple and convenient method of protein dynamics evaluation from the insufficient experimental N relaxation data is presented basing on the ratios, products, and differences of longitudinal and transverse N relaxation rates obtained at a single magnetic field. Firstly, the proposed approach allows evaluating overall tumbling correlation time (nanosecond time scale). Next, local parameters of the model-free approach characterizing local mobility of backbone amide N–H vectors on two different time scales, S and R, can be elucidated. The generalized order parameter, S, describes motions on the time scale faster than the overall tumbling correlation time (pico- to nanoseconds), while the chemical exchange term, R, identifies processes slower than the overall tumbling correlation time (micro- to milliseconds). Advantages and disadvantages of different methods of data handling are thoroughly discussed.

  19. Fast pairwise structural RNA alignments by pruning of the dynamical programming matrix.

    Jakob H Havgaard

    2007-10-01

    Full Text Available It has become clear that noncoding RNAs (ncRNA play important roles in cells, and emerging studies indicate that there might be a large number of unknown ncRNAs in mammalian genomes. There exist computational methods that can be used to search for ncRNAs by comparing sequences from different genomes. One main problem with these methods is their computational complexity, and heuristics are therefore employed. Two heuristics are currently very popular: pre-folding and pre-aligning. However, these heuristics are not ideal, as pre-aligning is dependent on sequence similarity that may not be present and pre-folding ignores the comparative information. Here, pruning of the dynamical programming matrix is presented as an alternative novel heuristic constraint. All subalignments that do not exceed a length-dependent minimum score are discarded as the matrix is filled out, thus giving the advantage of providing the constraints dynamically. This has been included in a new implementation of the FOLDALIGN algorithm for pairwise local or global structural alignment of RNA sequences. It is shown that time and memory requirements are dramatically lowered while overall performance is maintained. Furthermore, a new divide and conquer method is introduced to limit the memory requirement during global alignment and backtrack of local alignment. All branch points in the computed RNA structure are found and used to divide the structure into smaller unbranched segments. Each segment is then realigned and backtracked in a normal fashion. Finally, the FOLDALIGN algorithm has also been updated with a better memory implementation and an improved energy model. With these improvements in the algorithm, the FOLDALIGN software package provides the molecular biologist with an efficient and user-friendly tool for searching for new ncRNAs. The software package is available for download at http://foldalign.ku.dk.

  20. Dynamic analysis of the PEC fast reactor vessel: On-site tests and mathematical models

    Zola, M.; Martelli, A.; Masoni, P.; Scandola, G.

    1988-01-01

    This paper presents the main features and results of the on-site dynamic tests and the related numerical analyses carried out for the PEC reactor vessel. The purpose is to provide an example of on-site testing of large components, stressing the problems encountered during the experiments, as well as in the processing phase of the test results and for the comparisons between calculations and measurements. Tests, performed by ISMES on behalf of ENEA, allowed the dynamic response of the empty vessel to be measured, thus providing data for the verification of the numerical models of the vessel supporting structure adopted in the PEC reactor-block seismic analysis. An axisymmetric model of the vessel, implemented in the NOVAX code, had been developed in the framework of the detailed numerical studies performed by NOVATOME (again on behalf of ENEA), to check the beam schematization with fluid added mass model adopted by ANSALDO in SAP-IV and ANSYS for the reactor-block design calculations. Furthermore, a numerical model, describing vessel supporting structure in detail, was also developed by ANSALDO and implemented in the SAP-IV code. The test conditions were analysed by use of these and the design models. Comparisons between calculations and measurements showed particularly good agreement with regard to first natural frequency of the vessel and rocking stiffness of the vessel supporting structure, i.e. those parameters on which vessel seismic amplification mainly depends: this demonstrated the adequacy of the design analysis to correctly calculate the seismic motion at the PEC core diagrid. (author). 5 refs, 23 figs, 4 tabs

  1. Dynamic analysis of the PEC fast reactor vessel: on-site tests and mathematical models

    Zola, Maurizio; Martelli, Alessandro; Maresca, Giuseppe; Masoni, Paolo; Scandola, Giani; Descleves, Pierre

    1988-01-01

    This paper presents the main features and results of the on-site dynamic tests and the related numerical analysis carried out for the PEC reactor vessel. The purpose is to provide an example of on-site testing of large components, stressing the problems encountered during the experiments, as well as in the processing phase of the test results and for the comparisons between calculations and measurements. Tests, performed by ISMES on behalf of ENEA, allowed the dynamic response of the empty vessel to be measured, thus providing data for the verification of the numerical models of the vessel supporting structure adopted in the PEC reactor-block seismic analysis. An axisymmetric model of the vessel, implemented in the vessel, implemented in the NOVAK code, had been developed in the framework of the detailed numerical studies performed by NOVATOME (again on behalf of ENEA), to check the beam schematization with fluid added mass model adopted by ANSALDO in SAP-IV and ANSYS for the reactor-block design calculations. Furthermore, a numerical model, describing vessel supporting structure in detail, was also developed by ANSALDO and implemented in the SAP-IV code. The test conditions were analysed by use of these and the design models. Comparisons between calculations and measurements showed particularly good agreement with regard to first natural frequency of the vessel and rocking stiffness of the vessel supporting structure, i.e. those parameters on which vessel seismic amplification mainly depends: this demonstrated the adequacy of the design analysis to correctly calculate the seismic motion at the PEC core diagrid. (author)

  2. Dynamics of ultrathin metal films on amorphous substrates under fast thermal processing

    Favazza, Christopher; Kalyanaraman, Ramki; Sureshkumar, Radhakrishna

    2007-01-01

    A mathematical model is developed to analyze the growth/decay rate of surface perturbations of an ultrathin metal film on an amorphous substrate (SiO 2 ). The formulation combines the approach of Mullins [W. W. Mullins, J. Appl. Phys. 30, 77 (1959)] for bulk surfaces, in which curvature-driven mass transport and surface deformation can occur by surface/volume diffusion and evaporation-condensation processes, with that of Spencer et al. [B. J. Spencer, P. W. Voorhees, and S. H. Davis, Phys. Rev. Lett. 67, 26 (1991)] to describe solid-state transport in thin films under epitaxial strain. Modifications of the Mullins model to account for thin-film boundary conditions result in qualitatively different dispersion relationships especially in the limit as kh o o is the unperturbed film height. The model is applied to study the relative rate of solid-state mass transport as compared to that of liquid phase dewetting in a thin film subjected to a fast thermal pulse. Specifically, we have recently shown that multiple cycles of nanosecond (ns) pulsed laser melting and resolidification of ultrathin metal films on amorphous substrates can lead to the formation of various types of spatially ordered nanostructures [J. Trice, D. Thomas, C. Favazza, R. Sureshkumar, and R. Kalyanaraman, Phys. Rev. B 75, 235439 (2007)]. The pattern formation has been attributed to the dewetting of the thin film by a hydrodynamic instability. In such experiments the film is in the solid state during a substantial fraction of each thermal cycle. However, results of a linear stability analysis based on the aforementioned model suggest that solid-state mass transport has a negligible effect on morphological changes of the surface. Further, a qualitative analysis of the effect of thermoelastic stress, induced by the rapid temperature changes in the film-substrate bilayer, suggests that stress relaxation does not appreciably contribute to surface deformation. Hence, surface deformation caused by liquid

  3. Dynamics of ultrathin metal films on amorphous substrates under fast thermal processing

    Favazza, Christopher; Kalyanaraman, Ramki; Sureshkumar, Radhakrishna

    2007-11-01

    A mathematical model is developed to analyze the growth/decay rate of surface perturbations of an ultrathin metal film on an amorphous substrate (SiO2). The formulation combines the approach of Mullins [W. W. Mullins, J. Appl. Phys. 30, 77 (1959)] for bulk surfaces, in which curvature-driven mass transport and surface deformation can occur by surface/volume diffusion and evaporation-condensation processes, with that of Spencer etal . [B. J. Spencer, P. W. Voorhees, and S. H. Davis, Phys. Rev. Lett. 67, 26 (1991)] to describe solid-state transport in thin films under epitaxial strain. Modifications of the Mullins model to account for thin-film boundary conditions result in qualitatively different dispersion relationships especially in the limit as kho≪1, where k is the wavenumber of the perturbation and ho is the unperturbed film height. The model is applied to study the relative rate of solid-state mass transport as compared to that of liquid phase dewetting in a thin film subjected to a fast thermal pulse. Specifically, we have recently shown that multiple cycles of nanosecond (ns) pulsed laser melting and resolidification of ultrathin metal films on amorphous substrates can lead to the formation of various types of spatially ordered nanostructures [J. Trice, D. Thomas, C. Favazza, R. Sureshkumar, and R. Kalyanaraman, Phys. Rev. B 75, 235439 (2007)]. The pattern formation has been attributed to the dewetting of the thin film by a hydrodynamic instability. In such experiments the film is in the solid state during a substantial fraction of each thermal cycle. However, results of a linear stability analysis based on the aforementioned model suggest that solid-state mass transport has a negligible effect on morphological changes of the surface. Further, a qualitative analysis of the effect of thermoelastic stress, induced by the rapid temperature changes in the film-substrate bilayer, suggests that stress relaxation does not appreciably contribute to surface

  4. Protein kinase A (PKA) phosphorylation of Na+/K+-ATPase opens intracellular C-terminal water pathway leading to third Na+-binding site in molecular dynamics simulations

    Poulsen, Hanne; Nissen, Poul; Mouritsen, Ole G.

    2012-01-01

    -atom Molecular Dynamics (MD) simulations to investigate the structural consequences of phosphorylating the Na+/K+- ATPase (NKA) residue S936, which is the best characterized phosphorylation site in NKA, targeted in vivo by Protein Kinase A (PKA) (1-3). The MD simulations suggest that S936 phosphorylation opens......Phosphorylation is one of the major mechanisms for posttranscriptional modification of proteins. The addition of a compact, negatively charged moiety to a protein can significantly change its function and localization by affecting its structure and interaction network. We have used all...... a C-terminal hydrated pathway leading to D926, a transmembrane residue proposed to form part of the third sodium ion-binding site (4). Simulations of a S936E mutant form, for which only subtle effects are observed when expressed in Xenopus oocytes and studied with electrophysiology, does not mimic...

  5. Fast dynamic ventilation MRI of hyperpolarized 129 Xe using spiral imaging.

    Doganay, Ozkan; Matin, Tahreema N; Mcintyre, Anthony; Burns, Brian; Schulte, Rolf F; Gleeson, Fergus V; Bulte, Daniel

    2018-05-01

    To develop and optimize a rapid dynamic hyperpolarized 129 Xe ventilation (DXeV) MRI protocol and investigate the feasibility of capturing pulmonary signal-time curves in human lungs. Spiral k-space trajectories were designed with the number of interleaves N int  = 1, 2, 4, and 8 corresponding to voxel sizes of 8 mm, 5 mm, 4 mm, and 2.5 mm, respectively, for field of view = 15 cm. DXeV images were acquired from a gas-flow phantom to investigate the ability of N int  = 1, 2, 4, and 8 to capture signal-time curves. A finite element model was constructed to investigate gas-flow dynamics corroborating the experimental signal-time curves. DXeV images were also carried out in six subjects (three healthy and three chronic obstructive pulmonary disease subjects). DXeV images and numerical modelling of signal-time curves permitted the quantification of temporal and spatial resolutions for different numbers of spiral interleaves. The two-interleaved spiral (N int  = 2) was found to be the most time-efficient to obtain DXeV images and signal-time curves of whole lungs with a temporal resolution of 624 ms for 13 slices. Signal-time curves were well matched in three healthy volunteers. The Spearman's correlations of chronic obstructive pulmonary disease subjects were statistically different from three healthy subjects (P spiral demonstrates the successful acquisition of DXeV images and signal-time curves in healthy subjects and chronic obstructive pulmonary disease patients. Magn Reson Med 79:2597-2606, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc

  6. Application of fast pyrolysis biochar to a loamy soil - Effects on carbon and nitrogen dynamics and potential for carbon sequestration

    Bruun, E W

    2011-05-15

    Thermal decomposition of biomass in an oxygen-free environment (pyrolysis) produces bio-oil, syngas, and char. All three products can be used to generate energy, but an emerging new use of the recalcitrant carbon-rich char (biochar) is to apply it to the soil in order to enhance soil fertility and at the same time mitigate climate change by sequestering carbon in the soil. In general, the inherent physicochemical characteristics of biochars make these materials attractive agronomic soil conditioners. However, different pyrolysis technologies exist, i.e. slow pyrolysis, fast pyrolysis, and full gasification systems, and each of these influence the biochar quality differently. As of yet, there is only limited knowledge on the effect of applying fast pyrolysis biochar (FP-biochar) to soil. This PhD project provides new insights into the short-term impacts of adding FP-biochar to soil on the greenhouse gas (GHG) emissions and on soil carbon and nitrogen dynamics. The FP-biochars investigated in the thesis were generated at different reactor temperatures by fast pyrolysis of wheat straw employing a Pyrolysis Centrifuge Reactor (PCR). The carbohydrate content ranged from more than 35 % in FP-biochars made at a low reactor temperature (475 deg. C) down to 3 % in FP-biochars made at high temperatures (575 deg. C). The relative amount of carbohydrates in the FP-biochar was found to be correlated to the short-term degradation rates of the FP-biochars when applied to soil. Fast and slow pyrolysis of wheat straw resulted in two different biochar types with each their distinct physical structures and porosities, carbohydrate contents, particle sizes, pH values, BET surface areas, and elemental compositions. These different physicochemical properties obviously have different impacts on soil processes, which underscores that results obtained from soil studies using slow pyrolysis biochars (SP-biochar) are not necessarily applicable for FP-biochars. For example, the incorporation

  7. Application of fast pyrolysis biochar to a loamy soil - Effects on carbon and nitrogen dynamics and potential for carbon sequestration

    Bruun, E.W.

    2011-05-15

    Thermal decomposition of biomass in an oxygen-free environment (pyrolysis) produces bio-oil, syngas, and char. All three products can be used to generate energy, but an emerging new use of the recalcitrant carbon-rich char (biochar) is to apply it to the soil in order to enhance soil fertility and at the same time mitigate climate change by sequestering carbon in the soil. In general, the inherent physicochemical characteristics of biochars make these materials attractive agronomic soil conditioners. However, different pyrolysis technologies exist, i.e. slow pyrolysis, fast pyrolysis, and full gasification systems, and each of these influence the biochar quality differently. As of yet, there is only limited knowledge on the effect of applying fast pyrolysis biochar (FP-biochar) to soil. This PhD project provides new insights into the short-term impacts of adding FP-biochar to soil on the greenhouse gas (GHG) emissions and on soil carbon and nitrogen dynamics. The FP-biochars investigated in the thesis were generated at different reactor temperatures by fast pyrolysis of wheat straw employing a Pyrolysis Centrifuge Reactor (PCR). The carbohydrate content ranged from more than 35 % in FP-biochars made at a low reactor temperature (475 deg. C) down to 3 % in FP-biochars made at high temperatures (575 deg. C). The relative amount of carbohydrates in the FP-biochar was found to be correlated to the short-term degradation rates of the FP-biochars when applied to soil. Fast and slow pyrolysis of wheat straw resulted in two different biochar types with each their distinct physical structures and porosities, carbohydrate contents, particle sizes, pH values, BET surface areas, and elemental compositions. These different physicochemical properties obviously have different impacts on soil processes, which underscores that results obtained from soil studies using slow pyrolysis biochars (SP-biochar) are not necessarily applicable for FP-biochars. For example, the incorporation

  8. Dynamic simulation of a sodium-cooled fast reactor power plant

    Shinaishin, M.A.M.

    1976-08-01

    Simulation of the dynamic behavior of the Clinch River Breeder Reactor Plant (CRBRP) is the subject of this dissertation. The range of transients under consideration extends from a moderate transient, of the type referred to as Anticipated Transient Without Scram (ATWS), to a transient initiated by an unexpected accident followed by reactor scram. The moderate range of transients can be simulated by a digital simulator referred to as the CRBRP ATWS simulator. Two versions of this simulator were prepared; in one, the plant controllers were not included, whereas, in the other, the controllers were incorporated. A simulator referred to as the CRBRP-DCHT simulator was constructed for studying transients due to unexpected accidents followed by reactor scram. In this simulator emphasis was placed on simulating the auxiliary heat removal system, in order to determine its capability to remove the after-shut down fission and decay heat. The transients studied using the two versions of the ATWS simulator include step and ramp reactivity perturbations, and an electrical load perturbation in the controlled plant. An uncontrolled control rod withdrawal followed by reactor scram was studied using the DCHT simulator, although the duration of this transient was restricted to 20 sec. because of computer limitations. The results agree very well with the expected physical behavior of the plant.

  9. Ultra-fast bright field and fluorescence imaging of the dynamics of micrometer-sized objects

    Chen, Xucai; Wang, Jianjun; Versluis, Michel; de Jong, Nico; Villanueva, Flordeliza S.

    2013-06-01

    High speed imaging has application in a wide area of industry and scientific research. In medical research, high speed imaging has the potential to reveal insight into mechanisms of action of various therapeutic interventions. Examples include ultrasound assisted thrombolysis, drug delivery, and gene therapy. Visual observation of the ultrasound, microbubble, and biological cell interaction may help the understanding of the dynamic behavior of microbubbles and may eventually lead to better design of such delivery systems. We present the development of a high speed bright field and fluorescence imaging system that incorporates external mechanical waves such as ultrasound. Through collaborative design and contract manufacturing, a high speed imaging system has been successfully developed at the University of Pittsburgh Medical Center. We named the system "UPMC Cam," to refer to the integrated imaging system that includes the multi-frame camera and its unique software control, the customized modular microscope, the customized laser delivery system, its auxiliary ultrasound generator, and the combined ultrasound and optical imaging chamber for in vitro and in vivo observations. This system is capable of imaging microscopic bright field and fluorescence movies at 25 × 106 frames per second for 128 frames, with a frame size of 920 × 616 pixels. Example images of microbubble under ultrasound are shown to demonstrate the potential application of the system.

  10. Fast dynamics of Type I ELM and transport of ELM pulse in JT-60U

    Oyama, N.

    2002-01-01

    The mitigation of the large ELM heat load on the divertor target is one of the most important issues to be overcome on ITER. Since the ELM heat load strikes the divertor target not as a time-averaged load but as an instantaneous heat pulse, the evaluation of both ELM energy, and the time scale of the collapse and transport is very important. In JT-60U, the detailed dynamic behaviors of the collapse were measured using O-mode reflectometer. The duration of the collapse was within 0.35 ms and the lost pedestal density was recovered quickly within 0.5 ms. The collapse reached 10 cm inside the separatrix, which corresponds to twice the pedestal width of 5 cm. Dedicated edge density measurements on high- and low-field side revealed the poloidal asymmetry of the collapse of density pedestal for the first time. The measurement of SOL flow and heat load to the divertor target by using SOL Mach probe and IRTV showed that convective transport of the SOL plasma gave large contribution to the ELM heat deposition process. (author)

  11. Dynamic simulation of a sodium-cooled fast reactor power plant

    Shinaishin, M.A.M.

    1976-08-01

    Simulation of the dynamic behavior of the Clinch River Breeder Reactor Plant (CRBRP) is the subject of this dissertation. The range of transients under consideration extends from a moderate transient, of the type referred to as Anticipated Transient Without Scram (ATWS), to a transient initiated by an unexpected accident followed by reactor scram. The moderate range of transients can be simulated by a digital simulator referred to as the CRBRP ATWS simulator. Two versions of this simulator were prepared; in one, the plant controllers were not included, whereas, in the other, the controllers were incorporated. A simulator referred to as the CRBRP-DCHT simulator was constructed for studying transients due to unexpected accidents followed by reactor scram. In this simulator emphasis was placed on simulating the auxiliary heat removal system, in order to determine its capability to remove the after-shut down fission and decay heat. The transients studied using the two versions of the ATWS simulator include step and ramp reactivity perturbations, and an electrical load perturbation in the controlled plant. An uncontrolled control rod withdrawal followed by reactor scram was studied using the DCHT simulator, although the duration of this transient was restricted to 20 sec. because of computer limitations. The results agree very well with the expected physical behavior of the plant

  12. Further development of the fast beam dynamics simulation tool V-code

    Franke, Sylvain; Ackermann, Wolfgang; Weiland, Thomas [Institut fuer Theorie Elektromagnetischer Felder, TU Darmstadt (Germany)

    2010-07-01

    The Vlasov equation describes the evolution of a particle density under the effects of electromagnetic fields. It is derived from the fact that the volume occupied by a given number of particles in the six-dimensional phase space remains constant when only long-range interaction as for example Coulomb forces are relevant and other particle collisions can be neglected. Because this is the case for typical charged particle beams in accelerators, the Vlasov equation can be used to describe their evolution within the whole beam line. This equation is a partial differential equation in 6D and thus it is very expensive to solve it via classical numerical methods. A more efficient approach consists in representing the particle distribution function by a discrete set of characteristic moments. For each moment a time evolution equation can be stated. These ordinary differential equations can then be evaluated efficiently by means of time integration methods if all considered forces and a proper initial condition are known. The beam dynamics simulation tool V-Code implemented at TEMF utilizes this approach.

  13. Fully glutathione degradable waterborne polyurethane nanocarriers: Preparation, redox-sensitivity, and triggered intracellular drug release

    Omrani, Ismail; Babanejad, Niloofar; Shendi, Hasan Kashef; Nabid, Mohammad Reza, E-mail: m-nabid@sbu.ac.ir

    2017-01-01

    Polyurethanes are important class of biomaterials that are extensively used in medical devices. In spite of their easy synthesis, polyurethanes that are fully degradable in response to the intracellular reducing environment are less explored for controlled drug delivery. Herein, a novel glutathione degradable waterborne polyurethane (WPU) nanocarrier for redox triggered intracellular delivery of a model lipophilic anticancer drug, doxorubicin (DOX) is reported. The WPU was prepared from polyaddition reaction of isophorone diisocyanate (IPDI) and a novel linear polyester polyol involving disulfide linkage, disulfide labeled chain extender, dimethylolpropionic acid (DMPA) using dibutyltin dilaurate (DBTDL) as a catalyst. The resulting polyurethane self-assembles into nanocarrier in water. The dynamic light scattering (DLS) measurements and scanning electron microscope (SEM) revealed fast swelling and disruption of nanocarriers under an intracellular reduction-mimicking environment. The in vitro release studies showed that DOX was released in a controlled and redox-dependent manner. MTT assays showed that DOX-loaded WPU had a high in vitro antitumor activity in both HDF noncancer cells and MCF- 7 cancer cells. In addition, it is found that the blank WPU nanocarriers are nontoxic to HDF and MCF-7 cells even at a high concentration of 2 mg/mL. Hence, nanocarriers based on disulfide labeled WPU have appeared as a new class of biocompatible and redox-degradable nanovehicle for efficient intracellular drug delivery. - Highlights: • A novel fully glutathione degradable waterborne polyurethane was developed. • The waterborne nanocarrier with disulfide bonds in both hard and soft segment were developed for redox-triggered intracellular delivery of DOX. • The polyester diol bearing disulfide bonds in the backbone was prepared by a polycondensation polymerization reaction.

  14. Carnivora population dynamics are as slow and as fast as those of other mammals: implications for their conservation.

    Madelon van de Kerk

    Full Text Available Of the 285 species of Carnivora 71 are threatened, while many of these species fulfill important ecological roles in their ecosystems as top or meso-predators. Population transition matrices make it possible to study how age-specific survival and fecundity affect population growth, extinction risks, and responses to management strategies. Here we review 38 matrix models from 35 studies on 27 Carnivora taxa, covering 11% of the threatened Carnivora species. We show that the elasticity patterns (i.e. distribution over fecundity, juvenile survival and adult survival in Carnivora cover the same range in triangular elasticity plots as those of other mammal species, despite the specific place of Carnivora in the food chain. Furthermore, reproductive loop elasticity analysis shows that the studied species spread out evenly over a slow-fast continuum, but also quantifies the large variation in the duration of important life cycles and their contributions to population growth rate. These general elasticity patterns among species, and their correlation with simple life history characteristics like body mass, age of first reproduction and life span, enables the extrapolation of population dynamical properties to unstudied species. With several examples we discuss how this slow-fast continuum, and related patterns of variation in reproductive loop elasticity, can be used in the formulation of tentative management plans for threatened species that cannot wait for the results of thorough demographic studies. We argue, however, that such management programs should explicitly include a plan for learning about the key demographic rates and how these are affected by environmental drivers and threats.

  15. A computationally fast, reduced model for simulating landslide dynamics and tsunamis generated by landslides in natural terrains

    Mohammed, F.

    2016-12-01

    Landslide hazards such as fast-moving debris flows, slow-moving landslides, and other mass flows cause numerous fatalities, injuries, and damage. Landslide occurrences in fjords, bays, and lakes can additionally generate tsunamis with locally extremely high wave heights and runups. Two-dimensional depth-averaged models can successfully simulate the entire lifecycle of the three-dimensional landslide dynamics and tsunami propagation efficiently and accurately with the appropriate assumptions. Landslide rheology is defined using viscous fluids, visco-plastic fluids, and granular material to account for the possible landslide source materials. Saturated and unsaturated rheologies are further included to simulate debris flow, debris avalanches, mudflows, and rockslides respectively. The models are obtained by reducing the fully three-dimensional Navier-Stokes equations with the internal rheological definition of the landslide material, the water body, and appropriate scaling assumptions to obtain the depth-averaged two-dimensional models. The landslide and tsunami models are coupled to include the interaction between the landslide and the water body for tsunami generation. The reduced models are solved numerically with a fast semi-implicit finite-volume, shock-capturing based algorithm. The well-balanced, positivity preserving algorithm accurately accounts for wet-dry interface transition for the landslide runout, landslide-water body interface, and the tsunami wave flooding on land. The models are implemented as a General-Purpose computing on Graphics Processing Unit-based (GPGPU) suite of models, either coupled or run independently within the suite. The GPGPU implementation provides up to 1000 times speedup over a CPU-based serial computation. This enables simulations of multiple scenarios of hazard realizations that provides a basis for a probabilistic hazard assessment. The models have been successfully validated against experiments, past studies, and field data

  16. A simple three-dimensional-focusing, continuous-flow mixer for the study of fast protein dynamics.

    Burke, Kelly S; Parul, Dzmitry; Reddish, Michael J; Dyer, R Brian

    2013-08-07

    We present a simple, yet flexible microfluidic mixer with a demonstrated mixing time as short as 80 μs that is widely accessible because it is made of commercially available parts. To simplify the study of fast protein dynamics, we have developed an inexpensive continuous-flow microfluidic mixer, requiring no specialized equipment or techniques. The mixer uses three-dimensional, hydrodynamic focusing of a protein sample stream by a surrounding sheath solution to achieve rapid diffusional mixing between the sample and sheath. Mixing initiates the reaction of interest. Reactions can be spatially observed by fluorescence or absorbance spectroscopy. We characterized the pixel-to-time calibration and diffusional mixing experimentally. We achieved a mixing time as short as 80 μs. We studied the kinetics of horse apomyoglobin (apoMb) unfolding from the intermediate (I) state to its completely unfolded (U) state, induced by a pH jump from the initial pH of 4.5 in the sample stream to a final pH of 2.0 in the sheath solution. The reaction time was probed using the fluorescence of 1-anilinonaphthalene-8-sulfonate (1,8-ANS) bound to the folded protein. We observed unfolding of apoMb within 760 μs, without populating additional intermediate states under these conditions. We also studied the reaction kinetics of the conversion of pyruvate to lactate catalyzed by lactate dehydrogenase using the intrinsic tryptophan emission of the enzyme. We observe sub-millisecond kinetics that we attribute to Michaelis complex formation and loop domain closure. These results demonstrate the utility of the three-dimensional focusing mixer for biophysical studies of protein dynamics.

  17. High resolution polarimeter-interferometer system for fast equilibrium dynamics and MHD instability studies on Joint-TEXT tokamak (invited)

    Chen, J.; Zhuang, G., E-mail: ge-zhuang@hust.edu.cn; Li, Q.; Liu, Y.; Gao, L.; Zhou, Y. N.; Jian, X.; Xiong, C. Y.; Wang, Z. J. [State Key Laboratory of Advanced Electromagnetic Engineering and Technology, Huazhong University of Science and Technology, Wuhan 430074 (China); Brower, D. L.; Ding, W. X. [Department of Physics and Astronomy, University of California Los Angeles, Los Angeles, California 90095 (United States)

    2014-11-15

    A high-performance Faraday-effect polarimeter-interferometer system has been developed for the J-TEXT tokamak. This system has time response up to 1 μs, phase resolution < 0.1° and minimum spatial resolution ∼15 mm. High resolution permits investigation of fast equilibrium dynamics as well as magnetic and density perturbations associated with intrinsic Magneto-Hydro-Dynamic (MHD) instabilities and external coil-induced Resonant Magnetic Perturbations (RMP). The 3-wave technique, in which the line-integrated Faraday angle and electron density are measured simultaneously by three laser beams with specific polarizations and frequency offsets, is used. In order to achieve optimum resolution, three frequency-stabilized HCOOH lasers (694 GHz, >35 mW per cavity) and sensitive Planar Schottky Diode mixers are used, providing stable intermediate-frequency signals (0.5–3 MHz) with S/N > 50. The collinear R- and L-wave probe beams, which propagate through the plasma poloidal cross section (a = 0.25–0.27 m) vertically, are expanded using parabolic mirrors to cover the entire plasma column. Sources of systematic errors, e.g., stemming from mechanical vibration, beam non-collinearity, and beam polarization distortion are individually examined and minimized to ensure measurement accuracy. Simultaneous density and Faraday measurements have been successfully achieved for 14 chords. Based on measurements, temporal evolution of safety factor profile, current density profile, and electron density profile are resolved. Core magnetic and density perturbations associated with MHD tearing instabilities are clearly detected. Effects of non-axisymmetric 3D RMP in ohmically heated plasmas are directly observed by polarimetry for the first time.

  18. Real-Time linux dynamic clamp: a fast and flexible way to construct virtual ion channels in living cells.

    Dorval, A D; Christini, D J; White, J A

    2001-10-01

    We describe a system for real-time control of biological and other experiments. This device, based around the Real-Time Linux operating system, was tested specifically in the context of dynamic clamping, a demanding real-time task in which a computational system mimics the effects of nonlinear membrane conductances in living cells. The system is fast enough to represent dozens of nonlinear conductances in real time at clock rates well above 10 kHz. Conductances can be represented in deterministic form, or more accurately as discrete collections of stochastically gating ion channels. Tests were performed using a variety of complex models of nonlinear membrane mechanisms in excitable cells, including simulations of spatially extended excitable structures, and multiple interacting cells. Only in extreme cases does the computational load interfere with high-speed "hard" real-time processing (i.e., real-time processing that never falters). Freely available on the worldwide web, this experimental control system combines good performance. immense flexibility, low cost, and reasonable ease of use. It is easily adapted to any task involving real-time control, and excels in particular for applications requiring complex control algorithms that must operate at speeds over 1 kHz.

  19. Photodissociation dynamics of the methyl perthiyl radical at 248 and 193 nm using fast-beam photofragment translational spectroscopy

    Harrison, Aaron W.; Ryazanov, Mikhail; Sullivan, Erin N.; Neumark, Daniel M., E-mail: dneumark@berkeley.edu [Department of Chemistry, University of California, Berkeley, California 94720, USA and Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States)

    2016-07-14

    The photodissociation dynamics of the methyl perthiyl radical (CH{sub 3}SS) have been investigated using fast-beam coincidence translational spectroscopy. Methyl perthiyl radicals were produced by photodetachment of the CH{sub 3}SS{sup −} anion followed by photodissociation at 248 nm (5.0 eV) and 193 nm (6.4 eV). Photofragment mass distributions and translational energy distributions were measured at each dissociation wavelength. Experimental results show S atom loss as the dominant (96%) dissociation channel at 248 nm with a near parallel, anisotropic angular distribution and translational energy peaking near the maximal energy available to ground state CH{sub 3}S and S fragments, indicating that the dissociation occurs along a repulsive excited state. At 193 nm, S atom loss remains the major fragmentation channel, although S{sub 2} loss becomes more competitive and constitutes 32% of the fragmentation. The translational energy distributions for both channels are very broad at this wavelength, suggesting the formation of the S{sub 2} and S atom products in several excited electronic states.

  20. How Does the Ca2+-paradox Injury Induce Contracture in the Heart?—A Combined Study of the Intracellular Ca2+ Dynamics and Cell Structures in Perfused Rat Hearts—

    Mani, Hiroki; Tanaka, Hideo; Adachi, Tetsuya; Ikegawa, Masaya; Dai, Ping; Fujita, Naohisa; Takamatsu, Tetsuro

    2015-01-01

    The calcium (Ca 2+ )-paradox injury of the heart, induced by restoration of extracellular Ca 2+ after its short-term depletion, is known to provoke cardiomyocyte contracture. However, undetermined is how the Ca 2+ -paradox provokes such a distinctive presentation of myocytes in the heart. To address this, we imaged sequential intracellular Ca 2+ dynamics and concomitant structures of the subepicardial ventricular myocytes in fluo3-loaded, Langendorff-perfused rat hearts produced by the Ca 2+ paradox. Under rapid-scanning confocal microscopy, repletion of Ca 2+ following its depletion produced high-frequency Ca 2+ waves in individual myocytes with asynchronous localized contractions, resulting in contracture within 10 min. Such alterations of myocytes were attenuated by 5-mM NiCl 2 , but not by verapamil, SEA0400, or combination of ryanodine and thapsigargin, indicating a contribution of non-specific transmembrane Ca 2+ influx in the injury. However, saponin-induced membrane permeabilization of Ca 2+ showed no apparent contracture despite the emergence of high-frequency Ca 2+ waves, indicating an essential role of myocyte-myocyte and myocyte-extracellular matrix (ECM) mechanical connections in the Ca 2+ paradox. In immunohistochemistry Ca 2+ depletion produced separation of the intercalated disc that expresses cadherin and dissipation of β-dystroglycan located along the sarcolemma. Taken together, along with the trans-sarcolemmal Ca 2+ influx, disruption of cell-cell and cell-ECM connections is essential for contracture in the Ca 2+ -paradox injury

  1. Slow and fast dynamics model of a Malaria with Sickle-Cell genetic disease with multi-stage infections of the mosquitoes population

    Dewi Siawanta, Shanti; Adi-Kusumo, Fajar; Irwan Endrayanto, Aluicius

    2018-03-01

    Malaria, which is caused by Plasmodium, is a common disease in tropical areas. There are three types of Plasmodium i.e. Plasmodium Vivax, Plasmodium Malariae, and Plasmodium Falciparum. The most dangerous cases of the Malaria are mainly caused by the Plasmodium Falciparum. One of the important characteristics for the Plasmodium infection is due to the immunity of erythrocyte that contains HbS (Haemoglobin Sickle-cell) genes. The individuals who has the HbS gene has better immunity against the disease. In this paper, we consider a model that shows the spread of malaria involving the interaction between the mosquitos population, the human who has HbS genes population and the human with normal gene population. We do some analytical and numerical simulation to study the basic reproduction ratio and the slow-fast dynamics of the phase-portrait. The slow dynamics in our model represents the response of the human population with HbS gene to the Malaria disease while the fast dynamics show the response of the human population with the normal gene to the disease. The slow and fast dynamics phenomena are due to the fact that the population of the individuals who have HbS gene is much smaller than the individuals who has normal genes.

  2. Fast Dynamic Arrays

    Bille, Philip; Christiansen, Anders Roy; Ettienne, Mikko Berggren

    2017-01-01

    We present a highly optimized implementation of tiered vectors, a data structure for maintaining a sequence of n elements supporting access in time O(1) and insertion and deletion in time O(n) for > 0 while using o(n) extra space. We consider several different implementation optimizations in C...

  3. Hemodynamic analysis of bladder tumors using T1-dynamic contrast-enhanced fast spin-echo MRI

    Kanazawa, Yuki; Miyati, Tosiaki; Sato, Osamu

    2012-01-01

    Objectives: To evaluate the hemodynamics of bladder tumors, we developed a method to calculate change in R 1 value (ΔR 1 ) from T 1 -dynamic contrast-enhanced fast spin-echo magnetic resonance imaging (T 1 DCE-FSE-MRI). Materials and methods: On a 1.5-T MR system, T 1 DCE-FSE-MRI was performed. This study was applied to 12 patients with urinary bladder tumor, i.e. urothelial carcinoma. We compared ΔR 1 –time and ΔSI–time between a peak in the ΔR 1 –time and ΔSI–time curve occurred during the first pass within 60 s. Next, we assessed the slope of increase for 180 s after CA injection (Slope 0–180 ). Results: The mean slope of the first pass was significantly higher for bladder tumors on both the ΔR 1 –time and the ΔSI–time curve compared with normal bladder walls. Moreover, a significant difference was apparent between bladder tumors and normal bladder walls on the mean Slope 0–180 in the ΔR 1 -time curve. However, no significant difference in the mean Slope 0–180 was observed on the ΔSI-time curve between bladder tumors and normal bladder walls. Conclusion: T 1 DCE-FSE-MRI offers three advantages: quantitative analysis; high-quality (i.e., artifact-free) images; and high temporal resolution even for SE images. Use of ΔR 1 analysis with T 1 DCE-FSE-MRI allows more detailed information on the hemodynamics of bladder tumors to be obtained and assists in differentiation between bladder tumors and the normal bladder wall.

  4. Fast Virtual Fractional Flow Reserve Based Upon Steady-State Computational Fluid Dynamics Analysis: Results From the VIRTU-Fast Study.

    Morris, Paul D; Silva Soto, Daniel Alejandro; Feher, Jeroen F A; Rafiroiu, Dan; Lungu, Angela; Varma, Susheel; Lawford, Patricia V; Hose, D Rodney; Gunn, Julian P

    2017-08-01

    Fractional flow reserve (FFR)-guided percutaneous intervention is superior to standard assessment but remains underused. The authors have developed a novel "pseudotransient" analysis protocol for computing virtual fractional flow reserve (vFFR) based upon angiographic images and steady-state computational fluid dynamics. This protocol generates vFFR results in 189 s (cf >24 h for transient analysis) using a desktop PC, with <1% error relative to that of full-transient computational fluid dynamics analysis. Sensitivity analysis demonstrated that physiological lesion significance was influenced less by coronary or lesion anatomy (33%) and more by microvascular physiology (59%). If coronary microvascular resistance can be estimated, vFFR can be accurately computed in less time than it takes to make invasive measurements.

  5. Stochastic models of intracellular transport

    Bressloff, Paul C.; Newby, Jay M.

    2013-01-01

    mechanisms for intracellular transport: passive diffusion and motor-driven active transport. Diffusive transport can be formulated in terms of the motion of an overdamped Brownian particle. On the other hand, active transport requires chemical energy, usually

  6. Dynamic Processes in Biology, Chemistry, and Materials Science: Opportunities for UltraFast Transmission Electron Microscopy - Workshop Summary Report

    Kabius, Bernd C.; Browning, Nigel D.; Thevuthasan, Suntharampillai; Diehl, Barbara L.; Stach, Eric A.

    2012-07-25

    This report summarizes a 2011 workshop that addressed the potential role of rapid, time-resolved electron microscopy measurements in accelerating the solution of important scientific and technical problems. A series of U.S. Department of Energy (DOE) and National Academy of Science workshops have highlighted the critical role advanced research tools play in addressing scientific challenges relevant to biology, sustainable energy, and technologies that will fuel economic development without degrading our environment. Among the specific capability needs for advancing science and technology are tools that extract more detailed information in realistic environments (in situ or operando) at extreme conditions (pressure and temperature) and as a function of time (dynamic and time-dependent). One of the DOE workshops, Future Science Needs and Opportunities for Electron Scattering: Next Generation Instrumentation and Beyond, specifically addressed the importance of electron-based characterization methods for a wide range of energy-relevant Grand Scientific Challenges. Boosted by the electron optical advancement in the last decade, a diversity of in situ capabilities already is available in many laboratories. The obvious remaining major capability gap in electron microscopy is in the ability to make these direct in situ observations over a broad spectrum of fast (µs) to ultrafast (picosecond [ps] and faster) temporal regimes. In an effort to address current capability gaps, EMSL, the Environmental Molecular Sciences Laboratory, organized an Ultrafast Electron Microscopy Workshop, held June 14-15, 2011, with the primary goal to identify the scientific needs that could be met by creating a facility capable of a strongly improved time resolution with integrated in situ capabilities. The workshop brought together more than 40 leading scientists involved in applying and/or advancing electron microscopy to address important scientific problems of relevance to DOE’s research

  7. A three-dimensional thermal and fluid dynamics analysis of a gas cooled subcritical fast reactor driven by a D-T fusion neutron source

    Angelo, G.; Andrade, D.A.; Angelo, E.; Carluccio, T.; Rossi, P.C.R.; Talamo, A.

    2011-01-01

    Highlights: → A thermal fluid dynamics numerical model was created for a gas cooled subcritical fast reactor. → Standard k-ε model, Eddy Viscosity Transport Equation model underestimates the fuel temperature. → For a conservative assumption, SSG Reynolds stress model was chosen. → Creep strength is the most important parameter in fuel design. - Abstract: The entire nuclear fuel cycle involves partitioning classification and transmutation recycling. The usage of a tokamak as neutron sources to burn spent fuel in a gas cooled subcritical fast reactor (GCSFR) reduces the amount of long-lived radionuclide, thus increasing the repository capacity. This paper presents numerical thermal and fluid dynamics analysis for a gas cooled subcritical fast reactor. The analysis aim to determine the operational flow condition for this reactor, and to compare three distinct turbulence models (Eddy Viscosity Transport Equation, standard k-ε and SSG Reynolds stress) for this application. The model results are presented and discussed. The methodology used in this paper was developed to predict the coolant mass flow rate. It can be applied to any other gas cooled reactor.

  8. Development of the control assembly pattern and dynamic analysis of the Generation IV large gas-cooled fast reactor (GFR)

    Girardin, G.

    2009-07-15

    During the past ten years, different independent factors, such as the rapidly increasing worldwide demand in energy, societal concerns about greenhouse gas emissions, and the high and volatile prices for fossil fuels, have contributed to the renewed interest in nuclear technology. In this context, the Generation IV International Forum (GIF) launched the initiative to collaborate on the research and development efforts needed for the next generation of nuclear reactors. A particular goal set for Generation IV systems is closure of the nuclear fuel cycle; they are expected to offer a better utilization of natural resources, as also a minimization of long-lived radioactive wastes. Among the systems selected by the GIF, the Gas-cooled Fast Reactor (GFR) is a highly innovative system with advanced fuel geometry and materials. The principal aim of the present research is to develop and qualify the control assembly (CA) pattern and corresponding CA implementation scheme for the 2400 MWth reference GFR design. The work has been carried out in three successive phases: (1) validation of the neutronics tools, (2) the CA pattern development and related static analysis, and (3) dynamic core behaviour studies for hypothetical CA driven transients. The deterministic code system ERANOS and its associated nuclear data libraries for fast reactors were developed and validated for sodium-cooled reactors. In order to validate ERANOS for GFR applications, a systematic reanalysis of the GFR-relevant integral data generated at PSI during the GCFR-PROTEUS experimental program of the 1970’s was undertaken. The reference PROTEUS test lattice has been analyzed with ERANOS-2.0 and its associated, adjusted nuclear data library ERALIB1. Benchmark calculations were performed with the Monte Carlo code MCNPX, allowing one to both check the deterministic results and to analyze the sensitivity to different modern data libraries. For the main reaction rate ratios, the new analysis of the GCFR

  9. Development of the control assembly pattern and dynamic analysis of the Generation IV large gas-cooled fast reactor (GFR)

    Girardin, G.

    2009-07-01

    During the past ten years, different independent factors, such as the rapidly increasing worldwide demand in energy, societal concerns about greenhouse gas emissions, and the high and volatile prices for fossil fuels, have contributed to the renewed interest in nuclear technology. In this context, the Generation IV International Forum (GIF) launched the initiative to collaborate on the research and development efforts needed for the next generation of nuclear reactors. A particular goal set for Generation IV systems is closure of the nuclear fuel cycle; they are expected to offer a better utilization of natural resources, as also a minimization of long-lived radioactive wastes. Among the systems selected by the GIF, the Gas-cooled Fast Reactor (GFR) is a highly innovative system with advanced fuel geometry and materials. The principal aim of the present research is to develop and qualify the control assembly (CA) pattern and corresponding CA implementation scheme for the 2400 MWth reference GFR design. The work has been carried out in three successive phases: (1) validation of the neutronics tools, (2) the CA pattern development and related static analysis, and (3) dynamic core behaviour studies for hypothetical CA driven transients. The deterministic code system ERANOS and its associated nuclear data libraries for fast reactors were developed and validated for sodium-cooled reactors. In order to validate ERANOS for GFR applications, a systematic reanalysis of the GFR-relevant integral data generated at PSI during the GCFR-PROTEUS experimental program of the 1970’s was undertaken. The reference PROTEUS test lattice has been analyzed with ERANOS-2.0 and its associated, adjusted nuclear data library ERALIB1. Benchmark calculations were performed with the Monte Carlo code MCNPX, allowing one to both check the deterministic results and to analyze the sensitivity to different modern data libraries. For the main reaction rate ratios, the new analysis of the GCFR

  10. INTRACELLULAR Ca2+ HOMEOSTASIS

    Shahdevi Nandar Kurniawan

    2015-01-01

    Full Text Available Ca2+ signaling functions to regulate many cellular processes. Dynamics of Ca2+ signaling or homeostasis is regulated by the interaction between ON and OFF reactions that control Ca2+ flux in both the plasma membrane and internal organelles such as the endoplasmic reticulum (ER and mitochondria. External stimuli activate the ON reactions, which include Ca2+ into the cytoplasm either through channels in the plasma membrane or from internal storage like in ER. Most of the cells utilize both channels/sources, butthere area few cells using an external or internal source to control certain processes. Most of the Ca2+ entering the cytoplasm adsorbed to the buffer, while a smaller part activate effect or to stimulate cellular processes. Reaction OFF is pumping of cytoplasmic Ca2+ using a combination mechanism of mitochondrial and others. Changes in Ca2+ signal has been detected in various tissues isolated from animals induced into diabetes as well as patients with diabetes. Ca2+ signal interference is also found in sensory neurons of experimental animals with diabetes. Ca2+ signaling is one of the main signaling systems in the cell.

  11. Fast fission phenomena

    Gregoire, Christian.

    1982-03-01

    Experimental studies of fast fission phenomena are presented. The paper is divided into three parts. In the first part, problems associated with fast fission processes are examined in terms of interaction potentials and a dynamic model is presented in which highly elastic collisions, the formation of compound nuclei and fast fission appear naturally. In the second part, a description is given of the experimental methods employed, the observations made and the preliminary interpretation of measurements suggesting the occurence of fast fission processes. In the third part, our dynamic model is incorporated in a general theory of the dissipative processes studied. This theory enables fluctuations associated with collective variables to be calculated. It is applied to highly inelastic collisions, to fast fission and to the fission dynamics of compound nuclei (for which a schematic representation is given). It is with these calculations that the main results of the second part can be interpreted [fr

  12. Insecticide resistance and intracellular proteases.

    Wilkins, Richard M

    2017-12-01

    Pesticide resistance is an example of evolution in action with mechanisms of resistance arising from mutations or increased expression of intrinsic genes. Intracellular proteases have a key role in maintaining healthy cells and in responding to stressors such as pesticides. Insecticide-resistant insects have constitutively elevated intracellular protease activity compared to corresponding susceptible strains. This increase was shown for some cases originally through biochemical enzyme studies and subsequently putatively by transcriptomics and proteomics methods. Upregulation and expression of proteases have been characterised in resistant strains of some insect species, including mosquitoes. This increase in proteolysis results in more degradation products (amino acids) of intracellular proteins. These may be utilised in the resistant strain to better protect the cell from stress. There are changes in insect intracellular proteases shortly after insecticide exposure, suggesting a role in stress response. The use of protease and proteasome inhibitors or peptide mimetics as synergists with improved application techniques and through protease gene knockdown using RNA interference (possibly expressed in crop plants) may be potential pest management strategies, in situations where elevated intracellular proteases are relevant. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  13. A Method for Extracting the Free Energy Surface and Conformational Dynamics of Fast-Folding Proteins from Single Molecule Photon Trajectories

    2015-01-01

    Single molecule fluorescence spectroscopy holds the promise of providing direct measurements of protein folding free energy landscapes and conformational motions. However, fulfilling this promise has been prevented by technical limitations, most notably, the difficulty in analyzing the small packets of photons per millisecond that are typically recorded from individual biomolecules. Such limitation impairs the ability to accurately determine conformational distributions and resolve sub-millisecond processes. Here we develop an analytical procedure for extracting the conformational distribution and dynamics of fast-folding proteins directly from time-stamped photon arrival trajectories produced by single molecule FRET experiments. Our procedure combines the maximum likelihood analysis originally developed by Gopich and Szabo with a statistical mechanical model that describes protein folding as diffusion on a one-dimensional free energy surface. Using stochastic kinetic simulations, we thoroughly tested the performance of the method in identifying diverse fast-folding scenarios, ranging from two-state to one-state downhill folding, as a function of relevant experimental variables such as photon count rate, amount of input data, and background noise. The tests demonstrate that the analysis can accurately retrieve the original one-dimensional free energy surface and microsecond folding dynamics in spite of the sub-megahertz photon count rates and significant background noise levels of current single molecule fluorescence experiments. Therefore, our approach provides a powerful tool for the quantitative analysis of single molecule FRET experiments of fast protein folding that is also potentially extensible to the analysis of any other biomolecular process governed by sub-millisecond conformational dynamics. PMID:25988351

  14. On-site experimental dynamic analysis for evaluating the soil-structure interaction and the seismic behaviour of the Italian PEC fast reactor building

    Casirati, M.; Castoldi, A.; Panzeri, P.; Pezzoli, P.; Martelli, A.; Masoni, P.; Brancati, V.

    1988-01-01

    The paper describes the on-site dynamic tests carried out on the PEC fast reactor building, using various excitation methods (two eccentric back-rotating-mass mechanical vibrator, blasting in bore-hole, hydraulic actuators at the building foundations). It points out the purposes of the four tests campaigns performed at various construction stages and reports the main experimental results. These results concern both the design safety margins and the data for the validation of the three-dimensional numerical model of the reactor building, including soil-structure interaction phenomena. (author)

  15. Scattering of H(D) from LiF(1 0 0) under fast grazing incidence conditions: To what extent is classical dynamics a useful tool?

    Muzas, A.S. [Departamento de Química Módulo 13, Universidad Autónoma de Madrid, 28049 Madrid (Spain); Martín, F. [Departamento de Química Módulo 13, Universidad Autónoma de Madrid, 28049 Madrid (Spain); Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA-nanociencia), Cantoblanco, 28049 Madrid (Spain); Díaz, C., E-mail: cristina.diaz@uam.es [Departamento de Química Módulo 13, Universidad Autónoma de Madrid, 28049 Madrid (Spain)

    2015-07-01

    Diffraction experiments of atoms and molecules under fast grazing incidence conditions have opened a new field in surface science. This experimental effort calls for complementary theoretical studies, which would allow a detailed analysis of experimental data. Here, we have analyzed the ability of classical dynamics simulations to reproduce experimental results. To perform this study, a DFT (density functional theory) based potential energy surface, describing the interaction between a H atom and a LiF(1 0 0) surface, has been computed. Diffraction probabilities have been simulated by means of a classical binning method. Our results have been found to be in qualitative good agreement with recent experimental measurements.

  16. Development of the control assembly pattern and dynamic analysis of the generation IV large gas-cooled fast reactor (GFR)

    Girardin, G.

    2009-01-01

    Among the systems selected by the GIF, the Gas-cooled Fast Reactor (GFR) is a highly innovative system with advanced fuel geometry and materials. It is in the context of the large, 2400 MWth reference GFR design that the present doctoral research has been conducted, the principal aim having been to develop and qualify the control assembly (CA) pattern and corresponding CA implementation scheme for this system. The work has been carried out in three successive and complementary phases: (1) validation of the neutronics tools, (2) the CA pattern development and related static analysis, and (3) dynamic core behavior studies for hypothetical CA driven transients. During the first phase of the thesis, the reference PROTEUS test lattice from these experiments has been analyzed with ERANOS-2.0 and its associated, adjusted nuclear data library ERALIB1. Additionally, benchmark calculations were performed with the Monte Carlo code MCNPX, allowing one to both check the deterministic results and to analyze the sensitivity to different modern data libraries. It has been found that, for the main reaction rate ratios, the new analysis of the GCFR-PROTEUS reference lattice generally yields good agreement - within 1σ measurement uncertainty - with experimental values and with the Monte Carlo simulations. As shown by the analysis, the predictions were in somewhat better agreement in the case of the adjusted ERALIB1 library. The applicability of ERANOS-2.0/ERALIB1 as the reference neutronics tool for the GFR analysis could thus be demonstrated. Furthermore, neutronics aspects related to the novel features of the GFR, for which new experimental investigations are needed, were highlighted. In the second phase of the research, the CA pattern was developed for the GFR, based on iterative neutronics and thermal-hydraulics calculations, 2D and 3D neutronics models for the reactor core having first been set up using the reference ERANOS-2.0/ERALIB1 computational scheme. For the thermal

  17. Neutron dynamics of fast-spectrum dedicated cores for waste transmutation; Etude et amelioration du comportement cinetique de coeurs rapides a la transmutation de dechets a vie longue

    Massara, S

    2002-04-01

    Among different scenarios achieving minor actinide transmutation, the possibility of double strata scenarios with critical, fast spectrum, dedicated cores must be checked and quantified. In these cores, the waste fraction has to be at the highest level compatible with safety requirements during normal operation and transient conditions. As reactivity coefficients are poor in such critical cores (low delayed neutron fraction and Doppler feed-back, high coolant void coefficient), their dynamic behaviour during transient conditions must be carefully analysed. Three nitride-fuel configurations have been analysed: two liquid metal-cooled (sodium and lead) and a particle-fuel helium-cooled one. A dynamic code, MAT4 DYN, has been developed during the PhD thesis, allowing the study of loss of flow, reactivity insertion and loss of coolant accidents, and taking into account two fuel geometries (cylindrical and spherical) and two thermal-hydraulics models for the coolant (incompressible for liquid metals and compressible for helium). Dynamics calculations have shown that if the fuel nature is appropriately chosen (letting a sufficient margin during transients), this can counterbalance the bad state of reactivity coefficients for liquid metal-cooled cores, thus proving the interest of this kind of concept. On the other side, the gas-cooled core dynamics is very badly affected by the high value of the helium void coefficient (which is a consequence of the choice of a hard spectrum), this effect being amplified by the very low thermal inertia of particle-fuel design. So, a new kind of concept should be considered for a helium-cooled fast-spectrum dedicated core. (authors)

  18. The Influence of Cholesterol on Fast Dynamics Inside of Vesicle and Planar Phospholipid Bilayers Measured with 2D IR Spectroscopy.

    Kel, Oksana; Tamimi, Amr; Fayer, Michael D

    2015-07-23

    Phospholipid bilayers are frequently used as models for cell membranes. Here the influence of cholesterol on the structural dynamics in the interior of 1,2-dilauroyl-sn-glycero-3-phosphocholine (dilauroylphosphatidylcholine, DLPC) vesicles and DLPC planar bilayers are investigated as a function of cholesterol concentration. 2D IR vibrational echo spectroscopy was performed on the antisymmetric CO stretch of the vibrational probe molecule tungsten hexacarbonyl, which is located in the interior alkyl regions of the bilayers. The 2D IR experiments measure spectral diffusion, which is caused by the structural fluctuations of the bilayers. The 2D IR measurements show that the bilayer interior alkyl region dynamics occur on time scales ranging from a few picoseconds to many tens of picoseconds. These are the time scales of the bilayers' structural dynamics, which act as the dynamic solvent bath for chemical processes of membrane biomolecules. The results suggest that at least a significant fraction of the dynamics arise from density fluctuations. Samples are studied in which the cholesterol concentration is varied from 0% to 40% in both the vesicles (72 nm diameter) and fully hydrated planar bilayers in the form of aligned multibilayers. At all cholesterol concentrations, the structural dynamics are faster in the curved vesicle bilayers than in the planar bilayers. As the cholesterol concentration is increased, at a certain concentration there is a sudden change in the dynamics, that is, the dynamics abruptly slow down. However, this change occurs at a lower concentration in the vesicles (between 10% and 15% cholesterol) than in the planar bilayers (between 25% and 30% cholesterol). The sudden change in the dynamics, in addition to other IR observables, indicates a structural transition. However, the results show that the cholesterol concentration at which the transition occurs is influenced by the curvature of the bilayers.

  19. RAPID-L Highly Automated Fast Reactor Concept Without Any Control Rods (1) Reactor concept and plant dynamics analyses

    Kambe, Mitsuru; Tsunoda, Hirokazu; Mishima, Kaichiro; Iwamura, Takamichi

    2002-01-01

    The 200 kWe uranium-nitride fueled lithium cooled fast reactor concept 'RAPID-L' to achieve highly automated reactor operation has been demonstrated. RAPID-L is designed for Lunar base power system. It is one of the variants of RAPID (Refueling by All Pins Integrated Design), fast reactor concept, which enable quick and simplified refueling. The essential feature of RAPID concept is that the reactor core consists of an integrated fuel assembly instead of conventional fuel subassemblies. In this small size reactor core, 2700 fuel pins are integrated altogether and encased in a fuel cartridge. Refueling is conducted by replacing a fuel cartridge. The reactor can be operated without refueling for up to 10 years. Unique challenges in reactivity control systems design have been attempted in RAPID-L concept. The reactor has no control rod, but involves the following innovative reactivity control systems: Lithium Expansion Modules (LEM) for inherent reactivity feedback, Lithium Injection Modules (LIM) for inherent ultimate shutdown, and Lithium Release Modules (LRM) for automated reactor startup. All these systems adopt lithium-6 as a liquid poison instead of B 4 C rods. In combination with LEMs, LIMs and LRMs, RAPID-L can be operated without operator. This is the first reactor concept ever established in the world. This reactor concept is also applicable to the terrestrial fast reactors. In this paper, RAPID-L reactor concept and its transient characteristics are presented. (authors)

  20. The pelvis after surgery and radio-chemotherapy for rectal cancer studied with Gd-DTPA-enhanced fast dynamic MR imaging

    Blomqvist, L.; Fransson, P.; Hindmarsh, T.

    1998-01-01

    The aim of this work was to study the gadolinium-enhancement of malignant and benign pathology in the pelvis after surgery for rectal cancer. Thirty patients with either local recurrence (n = 17) or benign changes related to treatment for rectal cancer (n = 13) were studied with pelvic MR imaging. T2-weighted fast spin-echo as well as T1-weighted spin- or gradient-echo imaging before and after intravenous contrast was performed and referred to as contrast-enhanced MRI (CEMRI). In addition, between the pre- and postcontrast images, dynamic contrast-enhanced MRI (DCEMRI) was performed using a single-slice, multi-phase, contrast-enhanced T1-weighted fast spoiled gradient-echo sequence. The time between the start of contrast injection to the beginning of enhancement, the duration and rate of enhancement as well as enhancement amplitude were recorded. The data were compared with the clinical diagnosis according to biopsy in 8 patients and surgery in 6 patients. In the remaining 16 patients, the clinical diagnosis was obtained by clinical or radiological follow-up. DCEMRI did not improve the diagnostic information compared with CEMRI. None of the examined parameters were found to help discriminating malignant from benign changes. Characterisation of lesions in the pelvis after rectal cancer surgery was not improved by a dynamic gadolinium-enhanced sequence. (orig.)

  1. A coatable, light-weight, fast-response nanocomposite sensor for the in situ acquisition of dynamic elastic disturbance: from structural vibration to ultrasonic waves

    Zeng, Zhihui; Liu, Menglong; Xu, Hao; Liu, Weijian; Liao, Yaozhong; Jin, Hao; Zhou, Limin; Zhang, Zhong; Su, Zhongqing

    2016-06-01

    Inspired by an innovative sensing philosophy, a light-weight nanocomposite sensor made of a hybrid of carbon black (CB)/polyvinylidene fluoride (PVDF) has been developed. The nanoscalar architecture and percolation characteristics of the hybrid were optimized in order to fulfil the in situ acquisition of dynamic elastic disturbance from low-frequency vibration to high-frequency ultrasonic waves. Dynamic particulate motion induced by elastic disturbance modulates the infrastructure of the CB conductive network in the sensor, with the introduction of the tunneling effect, leading to dynamic alteration in the piezoresistivity measured by the sensor. Electrical analysis, morphological characterization, and static/dynamic electromechanical response interrogation were implemented to advance our insight into the sensing mechanism of the sensor, and meanwhile facilitate understanding of the optimal percolation threshold. At the optimal threshold (˜6.5 wt%), the sensor exhibits high fidelity, a fast response, and high sensitivity to ultrafast elastic disturbance (in an ultrasonic regime up to 400 kHz), yet with an ultralow magnitude (on the order of micrometers). The performance of the sensor was evaluated against a conventional strain gauge and piezoelectric transducer, showing excellent coincidence, yet a much greater gauge factor and frequency-independent piezoresistive behavior. Coatable on a structure and deployable in a large quantity to form a dense sensor network, this nanocomposite sensor has blazed a trail for implementing in situ sensing for vibration- or ultrasonic-wave-based structural health monitoring, by striking a compromise between ‘sensing cost’ and ‘sensing effectiveness’.

  2. Advanced parallel strategy for strongly coupled fast transient fluid-structure dynamics with dual management of kinematic constraints

    Faucher, Vincent

    2014-01-01

    Simulating fast transient phenomena involving fluids and structures in interaction for safety purposes requires both accurate and robust algorithms, and parallel computing to reduce the calculation time for industrial models. Managing kinematic constraints linking fluid and structural entities is thus a key issue and this contribution promotes a dual approach over the classical penalty approach, introducing arbitrary coefficients in the solution. This choice however severely increases the complexity of the problem, mainly due to non-permanent kinematic constraints. An innovative parallel strategy is therefore described, whose performances are demonstrated on significant examples exhibiting the full complexity of the target industrial simulations. (authors)

  3. Cationic Antimicrobial Peptide LL-37 Is Effective against both Extra- and Intracellular Staphylococcus aureus

    Noore, Jabeen; Noore, Adly

    2013-01-01

    The increasing resistance of bacteria to conventional antibiotics and the challenges posed by intracellular bacteria, which may be responsible for chronic and recurrent infections, have driven the need for advanced antimicrobial drugs for effective elimination of both extra- and intracellular pathogens. The purpose of this study was to determine the killing efficacy of cationic antimicrobial peptide LL-37 compared to conventional antibiotics against extra- and intracellular Staphylococcus aureus. Bacterial killing assays and an infection model of osteoblasts and S. aureus were studied to determine the bacterial killing efficacy of LL-37 and conventional antibiotics against extra- and intracellular S. aureus. We found that LL-37 was effective in killing extracellular S. aureus at nanomolar concentrations, while lactoferricin B was effective at micromolar concentrations and doxycycline and cefazolin at millimolar concentrations. LL-37 was surprisingly more effective in killing the clinical strain than in killing an ATCC strain of S. aureus. Moreover, LL-37 was superior to conventional antibiotics in eliminating intracellular S. aureus. The kinetic studies further revealed that LL-37 was fast in eliminating both extra- and intracellular S. aureus. Therefore, LL-37 was shown to be very potent and prompt in eliminating both extra- and intracellular S. aureus and was more effective in killing extra- and intracellular S. aureus than commonly used conventional antibiotics. LL-37 could potentially be used to treat chronic and recurrent infections due to its effectiveness in eliminating not only extracellular but also intracellular pathogens. PMID:23274662

  4. Stochastic models of intracellular transport

    Bressloff, Paul C.

    2013-01-09

    The interior of a living cell is a crowded, heterogenuous, fluctuating environment. Hence, a major challenge in modeling intracellular transport is to analyze stochastic processes within complex environments. Broadly speaking, there are two basic mechanisms for intracellular transport: passive diffusion and motor-driven active transport. Diffusive transport can be formulated in terms of the motion of an overdamped Brownian particle. On the other hand, active transport requires chemical energy, usually in the form of adenosine triphosphate hydrolysis, and can be direction specific, allowing biomolecules to be transported long distances; this is particularly important in neurons due to their complex geometry. In this review a wide range of analytical methods and models of intracellular transport is presented. In the case of diffusive transport, narrow escape problems, diffusion to a small target, confined and single-file diffusion, homogenization theory, and fractional diffusion are considered. In the case of active transport, Brownian ratchets, random walk models, exclusion processes, random intermittent search processes, quasi-steady-state reduction methods, and mean-field approximations are considered. Applications include receptor trafficking, axonal transport, membrane diffusion, nuclear transport, protein-DNA interactions, virus trafficking, and the self-organization of subcellular structures. © 2013 American Physical Society.

  5. Mycobacterium avium-intracellulare cellulitis occurring with septic arthritis after joint injection: a case report

    Murdoch David M

    2007-02-01

    Full Text Available Abstract Background Cellulitis caused by Mycobacterium avium-intracellulare has rarely been described. Mycobacterium avium-intracellulare is a rare cause of septic arthritis after intra-articular injection, though the causative role of injection is difficult to ascertain in such cases. Case presentation A 57-year-old with rheumatoid arthritis treated with prednisone and azathioprine developed bilateral painful degenerative shoulder arthritis. After corticosteroid injections into both acromioclavicular joints, he developed bilateral cellulitis centered over the injection sites. Skin biopsy showed non-caseating granulomas, and culture grew Mycobacterium avium-intracellulare. Joint aspiration also revealed Mycobacterium avium-intracellulare infection. Conclusion Although rare, skin and joint infections caused by Mycobacterium avium-intracellulare should be considered in any immunocompromised host, particularly after intra-articular injection. Stains for acid-fast bacilli may be negative in pathologic samples even in the presence of infection; cultures of tissue specimens should always be obtained.

  6. Value of fast dynamic enhanced MR imaging for the differential diagnosis between ovarian fibroma and subserosal leiomyoma

    Shan Jun; Wang Xiaomei; Xu Jianmin; Xu Hongli; Feng Xiaofeng; Gong Jingshan; Ling Rennan; Rao Zibin

    2004-01-01

    Objective: To study the value of dynamic enhanced MRI in the differential diagnosis between subserosal uterine leiomyoma and ovarian fibroma which were iso-signal and low signal ones on T 2 WI. Methods: Plain and dynamic enhanced MRI findings of 45 patients with histologically proved subserosal leiomyoma or ovarian fibroma were analyzed. There were 35 cases of subserosal leiomyoma and 10 cases of ovarian fibroma. The enhancement index of early phase (100 sec after the contrast medial administration) and the time to peak during 200 sec after the contrast administration (TTP 200 ) were analyzed. Results: On plain scanning, both subserosal leiomyoma and ovarian fibrioma appeared similarly as intrapelvic masses with low signal on T 2 WI. On Gadolinium dynamic enhancement, subserosal leiomyomas showed early and evident enhancement while ovarian fibroma showed delayed and moderate enhancement. The difference of the enhancement index of early phase and TTP 200 was statistically significant (P<0.001). Conclusion: Gadolinium dynamic enhanced MR imaging was helpful in the differential diagnosis between subserosal uterine leiomyoma and ovarian fibroma by the difference in the enhancement pattern

  7. Family of Step-up DC/DC Converters with Fast Dynamic Response for Low Power Applications

    N. Soltani, Mohsen; Mostaan, Ali; Siwakoti, Yam Prasad

    2016-01-01

    This study presents a family of novel step-up DC/DC converters which do not have a right half plane zero in their transfer function resulting in faster dynamic behaviour of the converters under the load variation. In addition, the voltage stress on all the active switches and diodes is as low...

  8. A molecular dynamics study of the effects of fast molecular motions on solid-state NMR parameters

    Dračínský, Martin; Hodgkinson, P.

    2013-01-01

    Roč. 15, č. 43 (2013), s. 8705-8712 ISSN 1466-8033 Grant - others:Seventh Framework Programme of the European Union(XE) FP7-299242 People Institutional support: RVO:61388963 Keywords : molecular dynamics * DFT calculations * NMR spectroscopy Subject RIV: CC - Organic Chemistry Impact factor: 3.858, year: 2013

  9. Fast “Feast/Famine” Cycles for Studying Microbial Physiology Under Dynamic Conditions : A Case Study with Saccharomyces cerevisiae

    Suarez-Mendez, C.A.; Sousa, A.; Heijnen, J.J.; Wahl, S.A.

    2014-01-01

    Microorganisms are constantly exposed to rapidly changing conditions, under natural as well as industrial production scale environments, especially due to large-scale substrate mixing limitations. In this work, we present an experimental approach based on a dynamic feast/famine regime (400 s) that

  10. Characterization of Leptin Intracellular Trafficking

    E Walum

    2009-12-01

    Full Text Available Leptin is produced by adipose tissue, and its concentration in plasma is related to the amount of fat in the body. The leptin receptor (OBR is a member of the class I cytokine receptor family and several different isoforms, produced by alternative mRNA splicing are found in many tissues, including the hypothalamus. The two predominant isoforms includes a long form (OBRl with an intracellular domain of 303 amino acids and a shorter form (OBRs with an intracellular domain of 34 amino acids. Since OBRl is mainly expressed in the hypotalamus, it has been suggested to be the main signalling form. The peripheral production of leptin by adipocyte tissue and its effects as a signal of satiety in the central nervous system imply that leptin gains access to regions of the brain regulating in energy balance by crossing the blood-brain barrier. In an attempt to characterize the intracellular transport of leptin, we have followed binding internalization and degradation of leptin in HEK293 cells. We have also monitored the intracellular transport pathway of fluorescent conjugated leptin in HEK293 cells. Phenylarsine oxide, a general inhibitor of endocytosis, as well as incubation at mild hypertonic conditions, prevented the uptake of leptin, confirming a receptor-mediated internalization process. When internalized, 125I-leptin was rapidly accumulated inside the cells and reached a maximum after 10 min. After 70 minutes about 40-50% of total counts in each time point were found in the medium as TCA-soluble material. Leptin sorting, at the level of early endosomes, did not seem to involve recycling endosomes, since FITC-leptin was sorted from Cy3- transferrin containing compartments at 37°C. At 45 minutes of continuos internalization, FITC-leptin appeared mainly accumulated in late endocytic structures colocalizing with internalized rhodamine coupled epidermial growth factor (EGF and the lysosomal marker protein lamp-1. The transport of leptin was also shown

  11. Exploring anti-bacterial compounds against intracellular Legionella.

    Christopher F Harrison

    Full Text Available Legionella pneumophila is a ubiquitous fresh-water bacterium which reproduces within its erstwhile predators, environmental amoeba, by subverting the normal pathway of phagocytosis and degradation. The molecular mechanisms which confer resistance to amoeba are apparently conserved and also allow replication within macrophages. Thus, L. pneumophila can act as an 'accidental' human pathogen and cause a severe pneumonia known as Legionnaires' disease. The intracellular localisation of L. pneumophila protects it from some antibiotics, and this fact must be taken into account to develop new anti-bacterial compounds. In addition, the intracellular lifestyle of L. pneumophila may render the bacteria susceptible to compounds diminishing bacterial virulence and decreasing intracellular survival and replication of this pathogen. The development of a single infection cycle intracellular replication assay using GFP-producing L. pneumophila and Acanthamoebacastellanii amoeba is reported here. This fluorescence-based assay allows for continuous monitoring of intracellular replication rates, revealing the effect of bacterial gene deletions or drug treatment. To examine how perturbations of the host cell affect L. pneumophila replication, several known host-targeting compounds were tested, including modulators of cytoskeletal dynamics, vesicle scission and Ras GTPase localisation. Our results reveal a hitherto unrealized potential antibiotic property of the β-lactone-based Ras depalmitoylation inhibitor palmostatin M, but not the closely related inhibitor palmostatin B. Further characterisation indicated that this compound caused specific growth inhibition of Legionella and Mycobacterium species, suggesting that it may act on a common bacterial target.

  12. Exploring Anti-Bacterial Compounds against Intracellular Legionella

    Harrison, Christopher F.; Kicka, Sébastien; Trofimov, Valentin; Berschl, Kathrin; Ouertatani-Sakouhi, Hajer; Ackermann, Nikolaus; Hedberg, Christian; Cosson, Pierre; Soldati, Thierry; Hilbi, Hubert

    2013-01-01

    Legionella pneumophila is a ubiquitous fresh-water bacterium which reproduces within its erstwhile predators, environmental amoeba, by subverting the normal pathway of phagocytosis and degradation. The molecular mechanisms which confer resistance to amoeba are apparently conserved and also allow replication within macrophages. Thus, L. pneumophila can act as an ‘accidental’ human pathogen and cause a severe pneumonia known as Legionnaires’ disease. The intracellular localisation of L. pneumophila protects it from some antibiotics, and this fact must be taken into account to develop new anti-bacterial compounds. In addition, the intracellular lifestyle of L. pneumophila may render the bacteria susceptible to compounds diminishing bacterial virulence and decreasing intracellular survival and replication of this pathogen. The development of a single infection cycle intracellular replication assay using GFP-producing L. pneumophila and Acanthamoeba castellanii amoeba is reported here. This fluorescence-based assay allows for continuous monitoring of intracellular replication rates, revealing the effect of bacterial gene deletions or drug treatment. To examine how perturbations of the host cell affect L. pneumophila replication, several known host-targeting compounds were tested, including modulators of cytoskeletal dynamics, vesicle scission and Ras GTPase localisation. Our results reveal a hitherto unrealized potential antibiotic property of the β-lactone-based Ras depalmitoylation inhibitor palmostatin M, but not the closely related inhibitor palmostatin B. Further characterisation indicated that this compound caused specific growth inhibition of Legionella and Mycobacterium species, suggesting that it may act on a common bacterial target. PMID:24058631

  13. Self-organization of intracellular gradients during mitosis

    Fuller Brian G

    2010-01-01

    Full Text Available Abstract Gradients are used in a number of biological systems to transmit spatial information over a range of distances. The best studied are morphogen gradients where information is transmitted over many cell lengths. Smaller mitotic gradients reflect the need to organize several distinct events along the length of the mitotic spindle. The intracellular gradients that characterize mitosis are emerging as important regulatory paradigms. Intracellular gradients utilize intrinsic auto-regulatory feedback loops and diffusion to establish stable regions of activity within the mitotic cytosol. We review three recently described intracellular mitotic gradients. The Ran GTP gradient with its elaborate cascade of nuclear transport receptors and cargoes is the best characterized, yet the dynamics underlying the robust gradient of Ran-GTP have received little attention. Gradients of phosphorylation have been observed on Aurora B kinase substrates both before and after anaphase onset. In both instances the phosphorylation gradient appears to result from a soluble gradient of Aurora B kinase activity. Regulatory properties that support gradient formation are highlighted. Intracellular activity gradients that regulate localized mitotic events bare several hallmarks of self-organizing biologic systems that designate spatial information during pattern formation. Intracellular pattern formation represents a new paradigm in mitotic regulation.

  14. A fast low-to-high confinement mode bifurcation dynamics in the boundary-plasma gyrokinetic code XGC1

    Ku, S.; Chang, C. S.; Hager, R.; Churchill, R. M.; Tynan, G. R.; Cziegler, I.; Greenwald, M.; Hughes, J.; Parker, S. E.; Adams, M. F.; D'Azevedo, E.; Worley, P.

    2018-05-01

    A fast edge turbulence suppression event has been simulated in the electrostatic version of the gyrokinetic particle-in-cell code XGC1 in a realistic diverted tokamak edge geometry under neutral particle recycling. The results show that the sequence of turbulent Reynolds stress followed by neoclassical ion orbit-loss driven together conspire to form the sustaining radial electric field shear and to quench turbulent transport just inside the last closed magnetic flux surface. The main suppression action is located in a thin radial layer around ψN≃0.96 -0.98 , where ψN is the normalized poloidal flux, with the time scale ˜0.1 ms.

  15. Dual time-resolved temperature-jump fluorescence and infrared spectroscopy for the study of fast protein dynamics.

    Davis, Caitlin M; Reddish, Michael J; Dyer, R Brian

    2017-05-05

    Time-resolved temperature-jump (T-jump) coupled with fluorescence and infrared (IR) spectroscopy is a powerful technique for monitoring protein dynamics. Although IR spectroscopy of the polypeptide amide I mode is more technically challenging, it offers complementary information because it directly probes changes in the protein backbone, whereas, fluorescence spectroscopy is sensitive to the environment of specific side chains. With the advent of widely tunable quantum cascade lasers (QCL) it is possible to efficiently probe multiple IR frequencies with high sensitivity and reproducibility. Here we describe a dual time-resolved T-jump fluorescence and IR spectrometer and its application to study protein folding dynamics. A Q-switched Ho:YAG laser provides the T-jump source for both time-resolved IR and fluorescence spectroscopy, which are probed by a QCL and Ti:Sapphire laser, respectively. The Ho:YAG laser simultaneously pumps the time-resolved IR and fluorescence spectrometers. The instrument has high sensitivity, with an IR absorbance detection limit of jump induced difference spectrum from 50ns to 0.5ms. This study demonstrates the power of the dual time-resolved T-jump fluorescence and IR spectroscopy to resolve complex folding mechanisms by complementary IR absorbance and fluorescence measurements of protein dynamics. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Second-order quadrupolar line shapes under molecular dynamics: An additional transition in the extremely fast regime.

    Hung, Ivan; Wu, Gang; Gan, Zhehong

    NMR spectroscopy is a powerful tool for probing molecular dynamics. For the classic case of two-site exchange, NMR spectra go through the transition from exchange broadening through coalescence and then motional narrowing as the exchange rate increases passing through the difference between the resonance frequencies of the two sites. For central-transition spectra of half-integer quadrupolar nuclei in solids, line shape change due to molecular dynamics occurs in two stages. The first stage occurs when the exchange rate is comparable to the second-order quadrupolar interaction. The second spectral transition comes at a faster exchange rate which approaches the Larmor frequency and generally reduces the isotropic quadrupolar shift. Such a two-stage transition phenomenon is unique to half-integer quadrupolar nuclei. A quantum mechanical formalism in full Liouville space is presented to explain the physical origin of the two-stage phenomenon and for use in spectral simulations. Variable-temperature 17 O NMR of solid NaNO 3 in which the NO 3 - ion undergoes 3-fold jumps confirms the two-stage transition process. The spectra of NaNO 3 acquired in the temperature range of 173-413K agree well with simulations using the quantum mechanical formalism. The rate constants for the 3-fold NO 3 - ion jumps span eight orders of magnitude (10 2 -10 10 s -1 ) covering both transitions of the dynamic 17 O line shape. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Cardiac function and perfusion dynamics measured on a beat-by-beat basis in the live mouse using ultra-fast 4D optoacoustic imaging

    Ford, Steven J.; Deán-Ben, Xosé L.; Razansky, Daniel

    2015-03-01

    The fast heart rate (~7 Hz) of the mouse makes cardiac imaging and functional analysis difficult when studying mouse models of cardiovascular disease, and cannot be done truly in real-time and 3D using established imaging modalities. Optoacoustic imaging, on the other hand, provides ultra-fast imaging at up to 50 volumetric frames per second, allowing for acquisition of several frames per mouse cardiac cycle. In this study, we combined a recently-developed 3D optoacoustic imaging array with novel analytical techniques to assess cardiac function and perfusion dynamics of the mouse heart at high, 4D spatiotemporal resolution. In brief, the heart of an anesthetized mouse was imaged over a series of multiple volumetric frames. In another experiment, an intravenous bolus of indocyanine green (ICG) was injected and its distribution was subsequently imaged in the heart. Unique temporal features of the cardiac cycle and ICG distribution profiles were used to segment the heart from background and to assess cardiac function. The 3D nature of the experimental data allowed for determination of cardiac volumes at ~7-8 frames per mouse cardiac cycle, providing important cardiac function parameters (e.g., stroke volume, ejection fraction) on a beat-by-beat basis, which has been previously unachieved by any other cardiac imaging modality. Furthermore, ICG distribution dynamics allowed for the determination of pulmonary transit time and thus additional quantitative measures of cardiovascular function. This work demonstrates the potential for optoacoustic cardiac imaging and is expected to have a major contribution toward future preclinical studies of animal models of cardiovascular health and disease.

  18. Bottom Fixed Platform Dynamics Models Assessing Surface Ice Interactions for Transitional Depth Structures in the Great Lakes: FAST8 – IceDyn

    Karr, Dale G. [Univ. of Michigan, Ann Arbor, MI (United States); Yu, Bingbin [Principle Power, Inc., Emeryville, CA (United States); Sirnivas, Senu [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2015-04-01

    To create long-term solutions for offshore wind turbines in a variety of environmental conditions, CAE tools are needed to model the design-driving loads that interact with an offshore wind turbine system during operation. This report describes our efforts in augmenting existing CAE tools used for offshore wind turbine analysis with a new module that can provide simulation capabilities for ice loading on the system. This augmentation was accomplished by creating an ice-loading module coupled to FAST8, the CAE tool maintained by the NREL for simulating land-based and offshore wind turbine dynamics. The new module includes both static and dynamic ice loading that can be applied during a dynamic simulation of the response of an offshore wind turbine. The ice forces can be prescribed, or influenced by the structure’s compliant response, or by the dynamics of both the structure and the ice floe. The new module covers ice failure modes of spalling, buckling, crushing, splitting, and bending. The supporting structure of wind turbines can be modeled as a vertical or sloping form at the waterline. The Inward Battered Guide Structure (IBGS) foundation designed by Keystone Engineering for the Great Lakes was used to study the ice models coupled to FAST8. The IBGS foundation ice loading simulations in FAST8 were compared to the baseline simulation case without ice loading. The ice conditions reflecting those from Lake Huron at Port Huron and Lake Michigan at North Manitou were studied under near rated wind speed of 12 m/s for the NREL 5-MW reference turbine. Simulations were performed on ice loading models 1 through 4 and ice model 6 with their respective sub-models. The purpose of ice model 5 is to investigate ice loading on sloping structures such as ice-cones on a monopile and is not suitable for multi-membered jacketed structures like the IBGS foundation. The key response parameters from the simulations, shear forces and moments from the tower base and IBGS foundation

  19. Electron Microscopy of Intracellular Protozoa

    1988-12-20

    Classification) " ELECTRON MICROSCOPY OF INTRACELLULAR PROTOZOA 12. PERSONAL AUTHOR(S) Aikawa, Masamichi 13a. TYPE OF REPORT I13b. TIME COVERED 114...authors suggest that anti-CS protein antibody is important in reducing the prevalence of malaria with increasing age among persons in such areas and... Hygine 33, 220-226. 0Giudice, G.D., Engers, H.D., Tougne, C., Biro, S.S., Weiss, N., Verdini, A.S., Pessi, A., Degremont, A.A., Freyvogel, T.A., Lambert

  20. Dopamine Dynamics during Continuous Intracranial Self-Stimulation: Effect of Waveform on Fast-Scan Cyclic Voltammetry Data

    2016-01-01

    The neurotransmitter dopamine is heavily implicated in intracranial self-stimulation (ICSS). Many drugs of abuse that affect ICSS behavior target the dopaminergic system, and optogenetic activation of dopamine neurons is sufficient to support self-stimulation. However, the patterns of phasic dopamine release during ICSS remain unclear. Early ICSS studies using fast-scan cyclic voltammetry (FSCV) rarely observed phasic dopamine release, which led to the surprising conclusion that it is dissociated from ICSS. However, several advances in the sensitivity (i.e., the use of waveforms with extended anodic limits) and analysis (i.e., principal component regression) of FSCV measurements have made it possible to detect smaller, yet physiologically relevant, dopamine release events. Therefore, this study revisits phasic dopamine release during ICSS using these tools. It was found that the anodic limit of the voltammetric waveform has a substantial effect on the patterns of dopamine release observed during continuous ICSS. While data collected with low anodic limits (i.e., +1.0 V) support the disappearance of phasic dopamine release observed in previous investigation, the use of high anodic limits (+1.3 V, +1.4 V) allows for continual detection of dopamine release throughout ICSS. However, the +1.4 V waveform lacks the ability to resolve narrowly spaced events, with the best balance of temporal resolution and sensitivity provided by the +1.3 V waveform. Ultimately, it is revealed that the amplitude of phasic dopamine release decays but does not fully disappear during continuous ICSS. PMID:27548680

  1. On a fast numerical tool for nuclear accidental dynamic phenomenology and application to the real time simulation of Lady Godiva

    Bindel, Laurent; Gamess, Andre; Jasserand, Frederic; Laporte, Sebastien

    2003-01-01

    This paper present a modern numerical method, implemented in a TUI-code named MacDSP, for solving any set of differential equations and in particular phenomenological accidental dynamic calculations. The speed efficiency of such an approach, thanks to the use of the hybrid-level power offered by C++ and an ad-hoc design, make it possible to construct the first kid of a family of real time simulator employing the video games technology DirectX TM : Lady Godiva Real Time Simulator. (author)

  2. Design of a large dynamics fast acquisition device: application to readout of the electromagnetic calorimeter in the ATLAS experiment

    Bussat, Jean-Marie

    1998-01-01

    The construction of the new particle accelerator, the LHC (Large Hadron Collider) at CERN is entails many research and development projects. It is the case in electronics where the problem of the acquisition of large dynamic range signals at high sampling frequencies occurs. Typically, the requirements are a dynamic range of about 65,000 (around 16 bits) at 40 MHz. Some solutions to this problem will be presented. One of them is using a commercial analog-to-digital converter. This case brings up the necessity of a signal conditioning equipment. This thesis describes a way of building such a system that will be called 'multi-gain system'. Then, an application of this method is presented. It involves the realization of an automatic gain switching integrated circuit. It is designed for the readout of the ATLAS electromagnetic calorimeter. The choice and the calculation of the components of this systems are described. They are followed by the results of some measurements done on a prototype made using the AMS 1.2μm BiCMOS foundry. Possible enhancements are also presented. We conclude on the feasibility of such a system and its various applications in a number of fields that are not restricted to particle physics. (author)

  3. Analysis of operator support method based on intelligent dynamic interlock in lead-cooled fast reactor simulator

    Xu, Peng; Wang, Jianye; Yang, Minghan; Wang, Weitian; Bai, Yunqing; Song, Yong

    2017-01-01

    Highlights: • We development an operator support method based on intelligent dynamic interlock. • We offer an integrated aid system to reduce the working strength of operators. • The method can help operators avoid dangerous, irreversible operation. • This method can be used in the fusion research reactor in the further. - Abstract: In nuclear systems, operators have to carry out corrective actions when abnormal situations occur. However, operators might make mistakes under pressure. In order to avoid serious consequences of the human errors, a new method for operators support based on intelligent dynamic interlock was proposed. The new method based on full digital instrumentation and control system, contains real-time alarm analysis process, decision support process and automatic safety interlock process. Once abnormal conditions occur, necessary safety interlock parameter based on analysis of real-time alarm and decision support process can be loaded into human-machine interfaces and controllers automatically, and avoid human errors effectively. Furthermore, the new method can make recommendations for further use and development of this technique in nuclear power plant or fusion research reactor.

  4. Development of effect assessment methodology for the deployment of fast reactor cycle system with dynamic computable general equilibrium model

    Shiotani, Hiroki; Ono, Kiyoshi

    2009-01-01

    The Global Trade and Analysis Project (GTAP) is a widely used computable general equilibrium (CGE) model developed by Purdue University. Although the GTAP-E, an energy environmental version of the GTAP model, is useful for surveying the energy-economy-environment-trade linkage is economic policy analysis, it does not have the decomposed model of the electricity sector and its analyses are comparatively static. In this study, a recursive dynamic CGE model with a detailed electricity technology bundle with nuclear power generation including FR was developed based on the GTAP-E to evaluate the long-term socioeconomic effects of FR deployment. The capital stock changes caused by international investments and some dynamic constraints of the FR deployment and operation (e.g., load following capability and plutonium mass balance) were incorporated in the analyses. The long-term socioeconomic effects resulting from the deployment of economic competitive FR with innovative technologies can be assessed; the cumulative effects of the FR deployment on GDP calculated using this model costed over 40 trillion yen in Japan and 400 trillion yen worldwide, which were several times more than the cost of the effects calculated using the conventional cost-benefit analysis tool, because of ripple effects and energy substitutions among others. (author)

  5. Fast isotropic banding-free bSSFP imaging using 3D dynamically phase-cycled radial bSSFP (3D DYPR-SSFP)

    Benkert, Thomas; Blaimer, Martin; Breuer, Felix A. [Research Center Magnetic Resonance Bavaria (MRB), Wuerzburg (Germany); Ehses, Philipp [Tuebingen Univ. (Germany). Dept. of Neuroimaging; Max Planck Institute for Biological Cybernetics, Tuebingen (Germany). High-Field MR Center; Jakob, Peter M. [Research Center Magnetic Resonance Bavaria (MRB), Wuerzburg (Germany); Wuerzburg Univ. (Germany). Dept. of Experimental Physics 5

    2016-05-01

    Aims: Dynamically phase-cycled radial balanced steady-state free precession (DYPR-SSFP) is a method for efficient banding artifact removal in bSSFP imaging. Based on a varying radiofrequency (RF) phase-increment in combination with a radial trajectory, DYPR-SSFP allows obtaining a banding-free image out of a single acquired k-space. The purpose of this work is to present an extension of this technique, enabling fast three-dimensional isotropic banding-free bSSFP imaging. Methods: While banding artifact removal with DYPR-SSFP relies on the applied dynamic phase-cycle, this aspect can lead to artifacts, at least when the number of acquired projections lies below a certain limit. However, by using a 3D radial trajectory with quasi-random view ordering for image acquisition, this problem is intrinsically solved, enabling 3D DYPR-SSFP imaging at or even below the Nyquist criterion. The approach is validated for brain and knee imaging at 3 Tesla. Results: Volumetric, banding-free images were obtained in clinically acceptable scan times with an isotropic resolution up to 0.56 mm. Conclusion: The combination of DYPR-SSFP with a 3D radial trajectory allows banding-free isotropic volumetric bSSFP imaging with no expense of scan time. Therefore, this is a promising candidate for clinical applications such as imaging of cranial nerves or articular cartilage.

  6. Pathogenic mechanisms of intracellular bacteria.

    Niller, Hans Helmut; Masa, Roland; Venkei, Annamária; Mészáros, Sándor; Minarovits, Janos

    2017-06-01

    We wished to overview recent data on a subset of epigenetic changes elicited by intracellular bacteria in human cells. Reprogramming the gene expression pattern of various host cells may facilitate bacterial growth, survival, and spread. DNA-(cytosine C5)-methyltransferases of Mycoplasma hyorhinis targeting cytosine-phosphate-guanine (CpG) dinucleotides and a Mycobacterium tuberculosis methyltransferase targeting non-CpG sites methylated the host cell DNA and altered the pattern of gene expression. Gene silencing by CpG methylation and histone deacetylation, mediated by cellular enzymes, also occurred in M. tuberculosis-infected macrophages. M. tuberculosis elicited cell type-specific epigenetic changes: it caused increased DNA methylation in macrophages, but induced demethylation, deposition of euchromatic histone marks and activation of immune-related genes in dendritic cells. A secreted transposase of Acinetobacter baumannii silenced a cellular gene, whereas Mycobacterium leprae altered the epigenotype, phenotype, and fate of infected Schwann cells. The 'keystone pathogen' oral bacterium Porphyromonas gingivalis induced local DNA methylation and increased the level of histone acetylation in host cells. These epigenetic changes at the biofilm-gingiva interface may contribute to the development of periodontitis. Epigenetic regulators produced by intracellular bacteria alter the epigenotype and gene expression pattern of host cells and play an important role in pathogenesis.

  7. Dynamical behaviour of fast electrons in a crystalline lamella; Comportement dynamique des electrons rapides dans une lamelle cristalline

    Perio, Pierre; Tournarie, Max [Commissariat a l' energie atomique et aux energies alternatives - CEA (France)

    1960-07-01

    The substitution of the reciprocal space by a 'mixed space' simplifies the use of the dynamical equation. The Friedel law is preserved. The Ventzel-Kramers-Brillouin-Rayleigh approximation appears as a planar approximation and explains the evolution of some images in electron microscopy. Reprint of a paper published in Comptes rendus des seances de l'Academie des Sciences, t. 249, p. 2218-2220, sitting of 23 November 1959 [French] La substitution d'un 'espace mixte' a l'espace reciproque facilite la manipulation de l'equation dynamique. La loi de Friedel est conservee. L'approximation Ventzel-Kramers-Brillouin-Rayleigh apparait comme une approximation plane et explique l'evolution de certaines images en microscopie electronique. Reproduction d'un article publie dans les Comptes rendus des seances de l'Academie des Sciences, t. 249, p. 2218-2220, seance du 23 novembre 1959.

  8. Fast neutron breeder reactor Rapsodie - situation of physics, hydraulic, thermal and dynamics studies and studies of stability early in 1963

    1964-01-01

    Early in 1963, it was necessary to make a choice among the two fuels examined for Rapsodie: the UPuMo alloy with double cladding, Nb and stainless steel, and the UO 2 -PuO 2 mix oxide. This report presents the results of the studies effected with the two types of fuel. We reconsider at first the different models which have been studied and we give a detailed description of the alloy and oxide cores as they are envisaged early in 1963. We give then the most important physics performances of the two cores: neutron flux and spectrum, reactivity of the compensation find safety rods, neutrons balance, specific power, effective fraction of delayed neutrons, lifetime of the prompt neutrons, reactivity coefficient. We describe the hydraulic studies and experiments which have been done concerning the two cores. We discuss the criteria adopted as basis for the flow calculations. We give the results of pressure drop and sub-assembly lifting, force measurements, and vibration and pin flow distribution experiments. We discuss the constants utilized for the thermal calculations and we give the temperatures of sodium and alloy or oxide fuel, the temperature increases due to the hot points, and the limitation of the oxide fuel burn-up, originated by the pressure of the fission gases. We treat the hypotheses having been utilized for the dynamics calculations and we describe the different accidents which have been studied. We give the results of the calculations for every accident and each fuel, and we show fuel melting or sodium boiling can be avoided, even in case of the most pessimistic hypotheses, by modifying reactor characteristics (shim-rod reactivity or power of the reactor with only one cooling circuit). The reactor stability has been evaluated with the hypotheses utilized for the dynamics calculations, except of the Doppler coefficient which was intentionally increased. We show that the alloy and oxide cores are stable for every envisaged reactor power. (authors) [fr

  9. MALDI-TOF Mass Spectrometry Enables a Comprehensive and Fast Analysis of Dynamics and Qualities of Stress Responses of Lactobacillus paracasei subsp. paracasei F19

    Schott, Ann-Sophie; Behr, Jürgen; Quinn, Jennifer; Vogel, Rudi F.

    2016-01-01

    Lactic acid bacteria (LAB) are widely used as starter cultures in the manufacture of foods. Upon preparation, these cultures undergo various stresses resulting in losses of survival and fitness. In order to find conditions for the subsequent identification of proteomic biomarkers and their exploitation for preconditioning of strains, we subjected Lactobacillus (Lb.) paracasei subsp. paracasei TMW 1.1434 (F19) to different stress qualities (osmotic stress, oxidative stress, temperature stress, pH stress and starvation stress). We analysed the dynamics of its stress responses based on the expression of stress proteins using MALDI-TOF mass spectrometry (MS), which has so far been used for species identification. Exploiting the methodology of accumulating protein expression profiles by MALDI-TOF MS followed by the statistical evaluation with cluster analysis and discriminant analysis of principle components (DAPC), it was possible to monitor the expression of low molecular weight stress proteins, identify a specific time point when the expression of stress proteins reached its maximum, and statistically differentiate types of adaptive responses into groups. Above the specific result for F19 and its stress response, these results demonstrate the discriminatory power of MALDI-TOF MS to characterize even dynamics of stress responses of bacteria and enable a knowledge-based focus on the laborious identification of biomarkers and stress proteins. To our knowledge, the implementation of MALDI-TOF MS protein profiling for the fast and comprehensive analysis of various stress responses is new to the field of bacterial stress responses. Consequently, we generally propose MALDI-TOF MS as an easy and quick method to characterize responses of microbes to different environmental conditions, to focus efforts of more elaborate approaches on time points and dynamics of stress responses. PMID:27783652

  10. MALDI-TOF Mass Spectrometry Enables a Comprehensive and Fast Analysis of Dynamics and Qualities of Stress Responses of Lactobacillus paracasei subsp. paracasei F19.

    Ann-Sophie Schott

    Full Text Available Lactic acid bacteria (LAB are widely used as starter cultures in the manufacture of foods. Upon preparation, these cultures undergo various stresses resulting in losses of survival and fitness. In order to find conditions for the subsequent identification of proteomic biomarkers and their exploitation for preconditioning of strains, we subjected Lactobacillus (Lb. paracasei subsp. paracasei TMW 1.1434 (F19 to different stress qualities (osmotic stress, oxidative stress, temperature stress, pH stress and starvation stress. We analysed the dynamics of its stress responses based on the expression of stress proteins using MALDI-TOF mass spectrometry (MS, which has so far been used for species identification. Exploiting the methodology of accumulating protein expression profiles by MALDI-TOF MS followed by the statistical evaluation with cluster analysis and discriminant analysis of principle components (DAPC, it was possible to monitor the expression of low molecular weight stress proteins, identify a specific time point when the expression of stress proteins reached its maximum, and statistically differentiate types of adaptive responses into groups. Above the specific result for F19 and its stress response, these results demonstrate the discriminatory power of MALDI-TOF MS to characterize even dynamics of stress responses of bacteria and enable a knowledge-based focus on the laborious identification of biomarkers and stress proteins. To our knowledge, the implementation of MALDI-TOF MS protein profiling for the fast and comprehensive analysis of various stress responses is new to the field of bacterial stress responses. Consequently, we generally propose MALDI-TOF MS as an easy and quick method to characterize responses of microbes to different environmental conditions, to focus efforts of more elaborate approaches on time points and dynamics of stress responses.

  11. TH-AB-207A-07: Radiation Dose Simulation for a Newly Proposed Dynamic Bowtie Filters for CT Using Fast Monte Carlo Methods

    Liu, T; Lin, H; Gao, Y; Caracappa, P; Wang, G; Cong, W; Xu, X [Rensselaer Polytechnic Institute, Troy, NY (United States)

    2016-06-15

    Purpose: Dynamic bowtie filter is an innovative design capable of modulating the X-ray and balancing the flux in the detectors, and it introduces a new way of patient-specific CT scan optimizations. This study demonstrates the feasibility of performing fast Monte Carlo dose calculation for a type of dynamic bowtie filter for cone-beam CT (Liu et al. 2014 9(7) PloS one) using MIC coprocessors. Methods: The dynamic bowtie filter in question consists of a highly attenuating bowtie component (HB) and a weakly attenuating bowtie (WB). The HB is filled with CeCl3 solution and its surface is defined by a transcendental equation. The WB is an elliptical cylinder filled with air and immersed in the HB. As the scanner rotates, the orientation of WB remains the same with the static patient. In our Monte Carlo simulation, the HB was approximated by 576 boxes. The phantom was a voxelized elliptical cylinder composed of PMMA and surrounded by air (44cm×44cm×40cm, 1000×1000×1 voxels). The dose to the PMMA phantom was tallied with 0.15% statistical uncertainty under 100 kVp source. Two Monte Carlo codes ARCHER and MCNP-6.1 were compared. Both used double-precision. Compiler flags that may trade accuracy for speed were avoided. Results: The wall time of the simulation was 25.4 seconds by ARCHER on a 5110P MIC, 40 seconds on a X5650 CPU, and 523 seconds by the multithreaded MCNP on the same CPU. The high performance of ARCHER is attributed to the parameterized geometry and vectorization of the program hotspots. Conclusion: The dynamic bowtie filter modeled in this study is able to effectively reduce the dynamic range of the detected signals for the photon-counting detectors. With appropriate software optimization methods, the accelerator-based (MIC and GPU) Monte Carlo dose engines have shown good performance and can contribute to patient-specific CT scan optimizations.

  12. Kinematic validation of a quasi-geostrophic model for the fast dynamics in the Earth's outer core

    Maffei, S.; Jackson, A.

    2017-09-01

    We derive a quasi-geostrophic (QG) system of equations suitable for the description of the Earth's core dynamics on interannual to decadal timescales. Over these timescales, rotation is assumed to be the dominant force and fluid motions are strongly invariant along the direction parallel to the rotation axis. The diffusion-free, QG system derived here is similar to the one derived in Canet et al. but the projection of the governing equations on the equatorial disc is handled via vertical integration and mass conservation is applied to the velocity field. Here we carefully analyse the properties of the resulting equations and we validate them neglecting the action of the Lorentz force in the momentum equation. We derive a novel analytical solution describing the evolution of the magnetic field under these assumptions in the presence of a purely azimuthal flow and an alternative formulation that allows us to numerically solve the evolution equations with a finite element method. The excellent agreement we found with the analytical solution proves that numerical integration of the QG system is possible and that it preserves important physical properties of the magnetic field. Implementation of magnetic diffusion is also briefly considered.

  13. The Tofts model in frequency domain: fast and robust determination of pharmacokinetic maps for dynamic contrast enhancement MRI

    Vajuvalli, Nithin N.; Chikkemenahally, Dharmendra Kumar K.; Nayak, Krupa N.; Bhosale, Manoj G.; Geethanath, Sairam

    2016-12-01

    Dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) is a well-established method for non-invasive detection and therapeutic monitoring of pathologies through administration of intravenous contrast agent. Quantification of pharmacokinetic (PK) maps can be achieved through application of compartmental models relevant to the pathophysiology of the tissue under interrogation. The determination of PK parameters involves fitting of time-concentration data to these models. In this work, the Tofts model in frequency domain (TM-FD) is applied to a weakly vascularized tissue such as the breast. It is derived as a convolution-free model from the conventional Tofts model in the time domain (TM-TD). This reduces the dimensionality of the curve-fitting problem from two to one. The approaches of TM-FD and TM-TD were applied to two kinds of in silico phantoms and six in vivo breast DCE data sets with and without the addition of noise. The results showed that computational time taken to estimate PK maps using TM-FD was 16-25% less than with TM-TD. Normalized root mean square error (NRMSE) calculation and Pearson correlation analyses were performed to validate robustness and accuracy of the TM-FD and TM-TD approaches. These compared with ground truth values in the case of phantom studies for four different temporal resolutions. Results showed that NRMSE values for TM-FD were significantly lower than those of TM-TD as validated by a paired t-test along with reduced computational time. This approach therefore enables online evaluation of PK maps by radiologists in a clinical setting, aiding in the evaluation of 3D and/or increased coverage of the tissue of interest.

  14. MR imaging of intracellular and extracellular deoxyhemoglobin

    Janick, P.A.; Grossman, R.I.; Asakura, T.

    1989-01-01

    MR imaging was performed on varying concentrations of intracellular and extracellular deoxyhemoglobin as well as varying proportions of deoxyhemoglobin and oxyhemoglobin in vitro at 1.5T with use of standard spin-echo and gradient-refocused spin sequences. This study indicates that susceptibility-induced T2 shortening occurs over a broad range of intracellular deoxyhemoglobin concentrations (maximal at hematocrits between 20% and 45%), reflecting diffusional effects at the cellular level. T2* gradient-echo imaging enhances the observed hypointensity in images of intracellular deoxyhemoglobin. The characteristic MR appearance of acute hemotomas can be modeled by the behavior of intracellular and extracellular deoxyhemoglobin and oxyhemoglobin

  15. Comparison of arterial input functions measured from ultra-fast dynamic contrast enhanced MRI and dynamic contrast enhanced computed tomography in prostate cancer patients

    Wang, Shiyang; Lu, Zhengfeng; Fan, Xiaobing; Medved, Milica; Jiang, Xia; Sammet, Steffen; Yousuf, Ambereen; Pineda, Federico; Oto, Aytekin; Karczmar, Gregory S.

    2018-02-01

    The purpose of this study was to evaluate the accuracy of arterial input functions (AIFs) measured from dynamic contrast enhanced (DCE) MRI following a low dose of contrast media injection. The AIFs measured from DCE computed tomography (CT) were used as ‘gold standard’. A total of twenty patients received CT and MRI scans on the same day. Patients received 120 ml Iohexol in DCE-CT and a low dose of (0.015 mM kg-1) of gadobenate dimeglumine in DCE-MRI. The AIFs were measured in the iliac artery and normalized to the CT and MRI contrast agent doses. To correct for different temporal resolution and sampling periods of CT and MRI, an empirical mathematical model (EMM) was used to fit the AIFs first. Then numerical AIFs (AIFCT and AIFMRI) were calculated based on fitting parameters. The AIFMRI was convolved with a ‘contrast agent injection’ function (AIFMRICON ) to correct for the difference between MRI and CT contrast agent injection times (~1.5 s versus 30 s). The results show that the EMMs accurately fitted AIFs measured from CT and MRI. There was no significant difference (p  >  0.05) between the maximum peak amplitude of AIFs from CT (22.1  ±  4.1 mM/dose) and MRI after convolution (22.3  ±  5.2 mM/dose). The shapes of the AIFCT and AIFMRICON were very similar. Our results demonstrated that AIFs can be accurately measured by MRI following low dose contrast agent injection.

  16. Effect of insulin resistance on intracellular signal transduction of vessels in diabetic

    Cen Rongguang; Wei Shaoying; Mo Xingju

    2003-01-01

    To investigate the relationship between the insulin resistance (IR) and the intracellular signal transduction of vessels, changes in fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), inositol triphosphate (IP 3 ), protein kinase C(PKC) and intracellular total calcium concentration in 31 diabetic patients were compared with those of 39 normal controls. The levels of FBG, FINS, TG and TC in diabetic patients were significantly higher than those of normal controls (P 3 and PKC in diabetic patients were significantly lower than those of normal controls (P<0.01). The results suggest that there is a causal relation between insulin resistance and abnormalities of cellular calcium metabolism and intracellular signal transduction of vessels

  17. Detection and quantification of intracellular bacterial colonies by automated, high-throughput microscopy

    Ernstsen, Christina L; Login, Frédéric H; Jensen, Helene H

    2017-01-01

    To target bacterial pathogens that invade and proliferate inside host cells, it is necessary to design intervention strategies directed against bacterial attachment, cellular invasion and intracellular proliferation. We present an automated microscopy-based, fast, high-throughput method for analy...

  18. Detection and quantification of intracellular bacterial colonies by automated, high-throughput microscopy.

    Ernstsen, Christina L; Login, Frédéric H; Jensen, Helene H; Nørregaard, Rikke; Møller-Jensen, Jakob; Nejsum, Lene N

    2017-08-01

    To target bacterial pathogens that invade and proliferate inside host cells, it is necessary to design intervention strategies directed against bacterial attachment, cellular invasion and intracellular proliferation. We present an automated microscopy-based, fast, high-throughput method for analyzing size and number of intracellular bacterial colonies in infected tissue culture cells. Cells are seeded in 48-well plates and infected with a GFP-expressing bacterial pathogen. Following gentamicin treatment to remove extracellular pathogens, cells are fixed and cell nuclei stained. This is followed by automated microscopy and subsequent semi-automated spot detection to determine the number of intracellular bacterial colonies, their size distribution, and the average number per host cell. Multiple 48-well plates can be processed sequentially and the procedure can be completed in one working day. As a model we quantified intracellular bacterial colonies formed by uropathogenic Escherichia coli (UPEC) during infection of human kidney cells (HKC-8). Urinary tract infections caused by UPEC are among the most common bacterial infectious diseases in humans. UPEC can colonize tissues of the urinary tract and is responsible for acute, chronic, and recurrent infections. In the bladder, UPEC can form intracellular quiescent reservoirs, thought to be responsible for recurrent infections. In the kidney, UPEC can colonize renal epithelial cells and pass to the blood stream, either via epithelial cell disruption or transcellular passage, to cause sepsis. Intracellular colonies are known to be clonal, originating from single invading UPEC. In our experimental setup, we found UPEC CFT073 intracellular bacterial colonies to be heterogeneous in size and present in nearly one third of the HKC-8 cells. This high-throughput experimental format substantially reduces experimental time and enables fast screening of the intracellular bacterial load and cellular distribution of multiple

  19. Computational Fluid Dynamics Simulation of Hydrodynamics and Stresses in the PhEur/USP Disintegration Tester Under Fed and Fasted Fluid Characteristics.

    Kindgen, Sarah; Wachtel, Herbert; Abrahamsson, Bertil; Langguth, Peter

    2015-09-01

    Disintegration of oral solid dosage forms is a prerequisite for drug dissolution and absorption and is to a large extent dependent on the pressures and hydrodynamic conditions in the solution that the dosage form is exposed to. In this work, the hydrodynamics in the PhEur/USP disintegration tester were investigated using computational fluid dynamics (CFD). Particle image velocimetry was used to validate the CFD predictions. The CFD simulations were performed with different Newtonian and non-Newtonian fluids, representing fasted and fed states. The results indicate that the current design and operating conditions of the disintegration test device, given by the pharmacopoeias, are not reproducing the in vivo situation. This holds true for the hydrodynamics in the disintegration tester that generates Reynolds numbers dissimilar to the reported in vivo situation. Also, when using homogenized US FDA meal, representing the fed state, too high viscosities and relative pressures are generated. The forces acting on the dosage form are too small for all fluids compared to the in vivo situation. The lack of peristaltic contractions, which generate hydrodynamics and shear stress in vivo, might be the major drawback of the compendial device resulting in the observed differences between predicted and in vivo measured hydrodynamics. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. On the Computing Potential of Intracellular Vesicles.

    Mayne, Richard; Adamatzky, Andrew

    2015-01-01

    Collision-based computing (CBC) is a form of unconventional computing in which travelling localisations represent data and conditional routing of signals determines the output state; collisions between localisations represent logical operations. We investigated patterns of Ca2+-containing vesicle distribution within a live organism, slime mould Physarum polycephalum, with confocal microscopy and observed them colliding regularly. Vesicles travel down cytoskeletal 'circuitry' and their collisions may result in reflection, fusion or annihilation. We demonstrate through experimental observations that naturally-occurring vesicle dynamics may be characterised as a computationally-universal set of Boolean logical operations and present a 'vesicle modification' of the archetypal CBC 'billiard ball model' of computation. We proceed to discuss the viability of intracellular vesicles as an unconventional computing substrate in which we delineate practical considerations for reliable vesicle 'programming' in both in vivo and in vitro vesicle computing architectures and present optimised designs for both single logical gates and combinatorial logic circuits based on cytoskeletal network conformations. The results presented here demonstrate the first characterisation of intracelluar phenomena as collision-based computing and hence the viability of biological substrates for computing.

  1. Single-cell intracellular nano-pH probes†

    Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

    2016-01-01

    Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular pH of individual cells within a cell population is challenging with existing technologies, and there is a need to engineer new methodologies. In this paper, we discuss the use of nanopipette technology to overcome the limitations of intracellular pH measurements at the single-cell level. We have developed a nano-pH probe through physisorption of chitosan onto hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of 0.09 units. We have performed single-cell intracellular pH measurements using non-cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231 and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time continuous single-cell pH measurement capability of the sensor, showing the cellular pH response to pharmaceutical manipulations. These findings suggest that the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at the single-cell level with high temporal and spatial resolution. PMID:27708772

  2. Single-cell intracellular nano-pH probes.

    Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

    2015-01-01

    Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular pH of individual cells within a cell population is challenging with existing technologies, and there is a need to engineer new methodologies. In this paper, we discuss the use of nanopipette technology to overcome the limitations of intracellular pH measurements at the single-cell level. We have developed a nano-pH probe through physisorption of chitosan onto hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of 0.09 units. We have performed single-cell intracellular pH measurements using non-cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231 and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time continuous single-cell pH measurement capability of the sensor, showing the cellular pH response to pharmaceutical manipulations. These findings suggest that the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at the single-cell level with high temporal and spatial resolution.

  3. Secretome of obligate intracellular Rickettsia

    Gillespie, Joseph J.; Kaur, Simran J.; Rahman, M. Sayeedur; Rennoll-Bankert, Kristen; Sears, Khandra T.; Beier-Sexton, Magda; Azad, Abdu F.

    2014-01-01

    The genus Rickettsia (Alphaproteobacteria, Rickettsiales, Rickettsiaceae) is comprised of obligate intracellular parasites, with virulent species of interest both as causes of emerging infectious diseases and for their potential deployment as bioterrorism agents. Currently, there are no effective commercially available vaccines, with treatment limited primarily to tetracycline antibiotics, although others (e.g. josamycin, ciprofloxacin, chloramphenicol, and azithromycin) are also effective. Much of the recent research geared toward understanding mechanisms underlying rickettsial pathogenicity has centered on characterization of secreted proteins that directly engage eukaryotic cells. Herein, we review all aspects of the Rickettsia secretome, including six secretion systems, 19 characterized secretory proteins, and potential moonlighting proteins identified on surfaces of multiple Rickettsia species. Employing bioinformatics and phylogenomics, we present novel structural and functional insight on each secretion system. Unexpectedly, our investigation revealed that the majority of characterized secretory proteins have not been assigned to their cognate secretion pathways. Furthermore, for most secretion pathways, the requisite signal sequences mediating translocation are poorly understood. As a blueprint for all known routes of protein translocation into host cells, this resource will assist research aimed at uniting characterized secreted proteins with their apposite secretion pathways. Furthermore, our work will help in the identification of novel secreted proteins involved in rickettsial ‘life on the inside’. PMID:25168200

  4. HYPERTHERMIA, INTRACELLULAR FREE CALCIUM AND CALCIUM IONOPHORES

    STEGE, GJJ; WIERENGA, PK; KAMPINGA, HH; KONINGS, AWT

    1993-01-01

    It is shown that heat-induced increase of intracellular calcium does not correlate with hyperthermic cell killing. Six different cell lines were investigated; in four (EAT, HeLa S3, L5178Y-R and L5178Y-S) heat treatments killing 90% of the cells did not affect the levels of intracellular free

  5. Intracellular localization of Arabidopsis sulfurtransferases.

    Bauer, Michael; Dietrich, Christof; Nowak, Katharina; Sierralta, Walter D; Papenbrock, Jutta

    2004-06-01

    Sulfurtransferases (Str) comprise a group of enzymes widely distributed in archaea, eubacteria, and eukaryota which catalyze the transfer of a sulfur atom from suitable sulfur donors to nucleophilic sulfur acceptors. In all organisms analyzed to date, small gene families encoding Str proteins have been identified. The gene products were localized to different compartments of the cells. Our interest concerns the localization of Str proteins encoded in the nuclear genome of Arabidopsis. Computer-based prediction methods revealed localization in different compartments of the cell for six putative AtStrs. Several methods were used to determine the localization of the AtStr proteins experimentally. For AtStr1, a mitochondrial localization was demonstrated by immunodetection in the proteome of isolated mitochondria resolved by one- and two-dimensional gel electrophoresis and subsequent blotting. The respective mature AtStr1 protein was identified by mass spectrometry sequencing. The same result was obtained by transient expression of fusion constructs with the green fluorescent protein in Arabidopsis protoplasts, whereas AtStr2 was exclusively localized to the cytoplasm by this method. Three members of the single-domain AtStr were localized in the chloroplasts as demonstrated by transient expression of green fluorescent protein fusions in protoplasts and stomata, whereas the single-domain AtStr18 was shown to be cytoplasmic. The remarkable subcellular distribution of AtStr15 was additionally analyzed by transmission electron immunomicroscopy using a monospecific antibody against green fluorescent protein, indicating an attachment to the thylakoid membrane. The knowledge of the intracellular localization of the members of this multiprotein family will help elucidate their specific functions in the organism.

  6. Intracellular calcium homeostasis and signaling.

    Brini, Marisa; Calì, Tito; Ottolini, Denis; Carafoli, Ernesto

    2013-01-01

    Ca(2+) is a universal carrier of biological information: it controls cell life from its origin at fertilization to its end in the process of programmed cell death. Ca(2+) is a conventional diffusible second messenger released inside cells by the interaction of first messengers with plasma membrane receptors. However, it can also penetrate directly into cells to deliver information without the intermediation of first or second messengers. Even more distinctively, Ca(2+) can act as a first messenger, by interacting with a plasma membrane receptor to set in motion intracellular signaling pathways that involve Ca(2+) itself. Perhaps the most distinctive property of the Ca(2+) signal is its ambivalence: while essential to the correct functioning of cells, Ca(2+) becomes an agent that mediates cell distress, or even (toxic) cell death, if its concentration and movements inside cells are not carefully tuned. Ca(2+) is controlled by reversible complexation to specific proteins, which could be pure Ca(2+) buffers, or which, in addition to buffering Ca(2+), also decode its signal to pass it on to targets. The most important actors in the buffering of cell Ca(2+) are proteins that transport it across the plasma membrane and the membrane of the organelles: some have high Ca(2+) affinity and low transport capacity (e.g., Ca(2+) pumps), others have opposite properties (e.g., the Ca(2+) uptake system of mitochondria). Between the initial event of fertilization, and the terminal event of programmed cell death, the Ca(2+) signal regulates the most important activities of the cell, from the expression of genes, to heart and muscle contraction and other motility processes, to diverse metabolic pathways involved in the generation of cell fuels.

  7. Dynamic surface-enhanced Raman spectroscopy and Chemometric methods for fast detection and intelligent identification of methamphetamine and 3, 4-Methylenedioxy methamphetamine in human urine

    Weng, Shizhuang; Dong, Ronglu; Zhu, Zede; Zhang, Dongyan; Zhao, Jinling; Huang, Linsheng; Liang, Dong

    2018-01-01

    Conventional Surface-Enhanced Raman Spectroscopy (SERS) for fast detection of drugs in urine on the portable Raman spectrometer remains challenges because of low sensitivity and unreliable Raman signal, and spectra process with manual intervention. Here, we develop a novel detection method of drugs in urine using chemometric methods and dynamic SERS (D-SERS) with mPEG-SH coated gold nanorods (GNRs). D-SERS combined with the uniform GNRs can obtain giant enhancement, and the signal is also of high reproducibility. On the basis of the above advantages, we obtained the spectra of urine, urine with methamphetamine (MAMP), urine with 3, 4-Methylenedioxy Methamphetamine (MDMA) using D-SERS. Simultaneously, some chemometric methods were introduced for the intelligent and automatic analysis of spectra. Firstly, the spectra at the critical state were selected through using K-means. Then, the spectra were proposed by random forest (RF) with feature selection and principal component analysis (PCA) to develop the recognition model. And the identification accuracy of model were 100%, 98.7% and 96.7%, respectively. To validate the effect in practical issue further, the drug abusers'urine samples with 0.4, 3, 30 ppm MAMP were detected using D-SERS and identified by the classification model. The high recognition accuracy of > 92.0% can meet the demand of practical application. Additionally, the parameter optimization of RF classification model was simple. Compared with the general laboratory method, the detection process of urine's spectra using D-SERS only need 2 mins and 2 μL samples volume, and the identification of spectra based on chemometric methods can be finish in seconds. It is verified that the proposed approach can provide the accurate, convenient and rapid detection of drugs in urine.

  8. Molecular dynamics simulation of subnanometric tool-workpiece contact on a force sensor-integrated fast tool servo for ultra-precision microcutting

    Cai, Yindi; Chen, Yuan-Liu; Shimizu, Yuki; Ito, So; Gao, Wei; Zhang, Liangchi

    2016-01-01

    Highlights: • Subnanometric contact between a diamond tool and a copper workpiece surface is investigated by MD simulation. • A multi-relaxation time technique is proposed to eliminate the influence of the atom vibrations. • The accuracy of the elastic-plastic transition contact depth estimation is improved by observing the residual defects. • The simulation results are beneficial for optimization of the next-generation microcutting instruments. - Abstract: This paper investigates the contact characteristics between a copper workpiece and a diamond tool in a force sensor-integrated fast tool servo (FS-FTS) for single point diamond microcutting and in-process measurement of ultra-precision surface forms of the workpiece. Molecular dynamics (MD) simulations are carried out to identify the subnanometric elastic-plastic transition contact depth, at which the plastic deformation in the workpiece is initiated. This critical depth can be used to optimize the FS-FTS as well as the cutting/measurement process. It is clarified that the vibrations of the copper atoms in the MD model have a great influence on the subnanometric MD simulation results. A multi-relaxation time method is then proposed to reduce the influence of the atom vibrations based on the fact that the dominant vibration component has a certain period determined by the size of the MD model. It is also identified that for a subnanometric contact depth, the position of the tool tip for the contact force to be zero during the retracting operation of the tool does not correspond to the final depth of the permanent contact impression on the workpiece surface. The accuracy for identification of the transition contact depth is then improved by observing the residual defects on the workpiece surface after the tool retracting.

  9. Nanoparticles for intracellular-targeted drug delivery

    Paulo, Cristiana S O; Pires das Neves, Ricardo; Ferreira, Lino S

    2011-01-01

    Nanoparticles (NPs) are very promising for the intracellular delivery of anticancer and immunomodulatory drugs, stem cell differentiation biomolecules and cell activity modulators. Although initial studies in the area of intracellular drug delivery have been performed in the delivery of DNA, there is an increasing interest in the use of other molecules to modulate cell activity. Herein, we review the latest advances in the intracellular-targeted delivery of short interference RNA, proteins and small molecules using NPs. In most cases, the drugs act at different cellular organelles and therefore the drug-containing NPs should be directed to precise locations within the cell. This will lead to the desired magnitude and duration of the drug effects. The spatial control in the intracellular delivery might open new avenues to modulate cell activity while avoiding side-effects.

  10. Biological synthesis and characterization of intracellular gold ...

    thods of reduction of metal ions using plants or microorganisms are often ... have several advantages over bacteria, they are often pre- ferred. ... in static condition for a period of 7 days. ... work was focused on the production of intracellular gold.

  11. Mycobacterium intracellulare Infection Mimicking Progression of Scleroderma

    Krabbe, Simon; Engelhart, Merete; Thybo, Sören

    2017-01-01

    This case report describes a patient with scleroderma who developed Mycobacterium intracellulare infection, which for more than a year mimicked worsening of her connective tissue disorder. The patient was diagnosed with scleroderma based on puffy fingers that developed into sclerodactyly, abnormal......, unfortunately with significant scarring. Immunodeficiency testing was unremarkable. In summary, an infection with Mycobacterium intracellulare was mistaken for an unusually severe progression of scleroderma....

  12. The fast code

    Freeman, L.N.; Wilson, R.E. [Oregon State Univ., Dept. of Mechanical Engineering, Corvallis, OR (United States)

    1996-09-01

    The FAST Code which is capable of determining structural loads on a flexible, teetering, horizontal axis wind turbine is described and comparisons of calculated loads with test data are given at two wind speeds for the ESI-80. The FAST Code models a two-bladed HAWT with degrees of freedom for blade bending, teeter, drive train flexibility, yaw, and windwise and crosswind tower motion. The code allows blade dimensions, stiffnesses, and weights to differ and models tower shadow, wind shear, and turbulence. Additionally, dynamic stall is included as are delta-3 and an underslung rotor. Load comparisons are made with ESI-80 test data in the form of power spectral density, rainflow counting, occurrence histograms, and azimuth averaged bin plots. It is concluded that agreement between the FAST Code and test results is good. (au)

  13. Fast harmonic field mapper

    Au, R.; Fowler, M.; Hanawa, H.; Riedel, J.; Qua, Z.G.

    1984-01-01

    In early 1983 it was decided to mount coils on arms separated by 120 degrees and buck them out so that the third harmonic dphi/dt component would be cancelled and thus the first and second field harmonics could be very accurately measured. The original intention was to do as others had done, namely, use fast ADC's to read the voltages, and computer process the result to get the Fourier components. However, because of the 100 to 1 dynamic range of the fast ADC's and the likelihood that noise would be a problem, the authors decided to do things differently. Using a fast Fourier transform analyzer was considered, but this instrument is very expensive, so they decided to use a completely electronic analog approach: The authors decided to use active bandpass filters to render the harmonic components

  14. Fast reactors

    Vasile, A.

    2001-01-01

    Fast reactors have capacities to spare uranium natural resources by their breeding property and to propose solutions to the management of radioactive wastes by limiting the inventory of heavy nuclei. This article highlights the role that fast reactors could play for reducing the radiotoxicity of wastes. The conversion of 238 U into 239 Pu by neutron capture is more efficient in fast reactors than in light water reactors. In fast reactors multi-recycling of U + Pu leads to fissioning up to 95% of the initial fuel ( 238 U + 235 U). 2 strategies have been studied to burn actinides: - the multi-recycling of heavy nuclei is made inside the fuel element (homogeneous option); - the unique recycling is made in special irradiation targets placed inside the core or at its surroundings (heterogeneous option). Simulations have shown that, for the same amount of energy produced (400 TWhe), the mass of transuranium elements (Pu + Np + Am + Cm) sent to waste disposal is 60,9 Kg in the homogeneous option and 204.4 Kg in the heterogeneous option. Experimental programs are carried out in Phenix and BOR60 reactors in order to study the feasibility of such strategies. (A.C.)

  15. Fast ejendom

    Pagh, Peter

    Bogen omfatter en gennemgang af lovgivning, praksis og teori vedrørende køb af fast ejendom og offentligretlig og privatretlig regulering. Bogen belyser bl.a. de privatretlige emner: købers misligholdelsesbeføjelser, servitutter, naboret, hævd og erstatningsansvar for miljøskader samt den...

  16. Efficient intracellular delivery and improved biocompatibility of colloidal silver nanoparticles towards intracellular SERS immuno-sensing.

    Bhardwaj, Vinay; Srinivasan, Supriya; McGoron, Anthony J

    2015-06-21

    High throughput intracellular delivery strategies, electroporation, passive and TATHA2 facilitated diffusion of colloidal silver nanoparticles (AgNPs) are investigated for cellular toxicity and uptake using state-of-art analytical techniques. The TATHA2 facilitated approach efficiently delivered high payload with no toxicity, pre-requisites for intracellular applications of plasmonic metal nanoparticles (PMNPs) in sensing and therapeutics.

  17. Investigating Internalization and Intracellular Trafficking of GPCRs

    Foster, Simon R; Bräuner-Osborne, Hans

    2017-01-01

    for signal transduction. One of the major mechanisms for GPCR regulation involves their endocytic trafficking, which serves to internalize the receptors from the plasma membrane and thereby attenuate G protein-dependent signaling. However, there is accumulating evidence to suggest that GPCRs can signal...... independently of G proteins, as well as from intracellular compartments including endosomes. It is in this context that receptor internalization and intracellular trafficking have attracted renewed interest within the GPCR field. In this chapter, we will review the current understanding and methodologies...

  18. Model-based control of the temporal patterns of intracellular signaling in silico

    Murakami, Yohei; Koyama, Masanori; Oba, Shigeyuki; Kuroda, Shinya; Ishii, Shin

    2017-01-01

    The functions of intracellular signal transduction systems are determined by the temporal behavior of intracellular molecules and their interactions. Of the many dynamical properties of the system, the relationship between the dynamics of upstream molecules and downstream molecules is particularly important. A useful tool in understanding this relationship is a methodology to control the dynamics of intracellular molecules with an extracellular stimulus. However, this is a difficult task because the relationship between the levels of upstream molecules and those of downstream molecules is often not only stochastic, but also time-inhomogeneous, nonlinear, and not one-to-one. In this paper, we present an easy-to-implement model-based control method that makes the target downstream molecule to trace a desired time course by changing the concentration of a controllable upstream molecule. Our method uses predictions from Monte Carlo simulations of the model to decide the strength of the stimulus, while using a particle-based approach to make inferences regarding unobservable states. We applied our method to in silico control problems of insulin-dependent AKT pathway model and EGF-dependent Akt pathway model with system noise. We show that our method can robustly control the dynamics of the intracellular molecules against unknown system noise of various strengths, even in the absence of complete knowledge of the true model of the target system. PMID:28275530

  19. When transcriptome meets metabolome : Fast cellular responses of yeast to sudden relief of glucose limitation

    Heijnen, J.J.; Daran, J.M.; Pronk, J.T.; Daran-Lapujade, P.; Knijnenburg, T.A.; Ras, C.; Ten Pierick, A.; Akmering, M.J.; Van Winden, W.A.; Kresnowati, M.T.

    2006-01-01

    Within the first 5 min after a sudden relief from glucose limitation, Saccharomyces cerevisiae exhibited fast changes of intracellular metabolite levels and a major transcriptional reprogramming. Integration of transcriptome and metabolome data revealed tight relationships between the changes at

  20. Dynamics

    Goodman, Lawrence E

    2001-01-01

    Beginning text presents complete theoretical treatment of mechanical model systems and deals with technological applications. Topics include introduction to calculus of vectors, particle motion, dynamics of particle systems and plane rigid bodies, technical applications in plane motions, theory of mechanical vibrations, and more. Exercises and answers appear in each chapter.

  1. Cationic polymers for intracellular delivery of proteins

    Coué, G.M.J.P.C.; Engbersen, Johannes F.J.; Samal, Sangram; Dubruel, Peter

    2015-01-01

    Many therapeutic proteins exert their pharmaceutical action inside the cytoplasm or onto individual organelles inside the cell. Intracellular protein delivery is considered to be the most direct, fastest and safest approach for curing gene-deficiency diseases, enhancing vaccination and triggering

  2. Molecular detection and characterization of sustainable intracellular ...

    3Centre for Biopolymer and Bio-Molecular Research, Athlone College of Technology, Republic of Ireland. ... cells was associated with the elongation of micro-villar extension that ... Keywords: Intracellular contaminants, cell cultures, bacteria culture, pre-clinical studies. ... production work involving culture technology.

  3. Spatial Cytoskeleton Organization Supports Targeted Intracellular Transport

    Hafner, Anne E.; Rieger, Heiko

    2018-03-01

    The efficiency of intracellular cargo transport from specific source to target locations is strongly dependent upon molecular motor-assisted motion along the cytoskeleton. Radial transport along microtubules and lateral transport along the filaments of the actin cortex underneath the cell membrane are characteristic for cells with a centrosome. The interplay between the specific cytoskeleton organization and the motor performance realizes a spatially inhomogeneous intermittent search strategy. In order to analyze the efficiency of such intracellular search strategies we formulate a random velocity model with intermittent arrest states. We evaluate efficiency in terms of mean first passage times for three different, frequently encountered intracellular transport tasks: i) the narrow escape problem, which emerges during cargo transport to a synapse or other specific region of the cell membrane, ii) the reaction problem, which considers the binding time of two particles within the cell, and iii) the reaction-escape problem, which arises when cargo must be released at a synapse only after pairing with another particle. Our results indicate that cells are able to realize efficient search strategies for various intracellular transport tasks economically through a spatial cytoskeleton organization that involves only a narrow actin cortex rather than a cell body filled with randomly oriented actin filaments.

  4. Biological synthesis and characterization of intracellular gold ...

    In the present study, Aspergillus fumigatus was used for the intracellular synthesis of gold nanoparticles. Stable nanoparticles were produced when an aqueous solution of chloroauric acid (HAuCl4) was reduced by A. fumigatus biomass as the reducing agent. Production of nanoparticles was confirmed by the colour ...

  5. Optimizing Nanoelectrode Arrays for Scalable Intracellular Electrophysiology.

    Abbott, Jeffrey; Ye, Tianyang; Ham, Donhee; Park, Hongkun

    2018-03-20

    Electrode technology for electrophysiology has a long history of innovation, with some decisive steps including the development of the voltage-clamp measurement technique by Hodgkin and Huxley in the 1940s and the invention of the patch clamp electrode by Neher and Sakmann in the 1970s. The high-precision intracellular recording enabled by the patch clamp electrode has since been a gold standard in studying the fundamental cellular processes underlying the electrical activities of neurons and other excitable cells. One logical next step would then be to parallelize these intracellular electrodes, since simultaneous intracellular recording from a large number of cells will benefit the study of complex neuronal networks and will increase the throughput of electrophysiological screening from basic neurobiology laboratories to the pharmaceutical industry. Patch clamp electrodes, however, are not built for parallelization; as for now, only ∼10 patch measurements in parallel are possible. It has long been envisioned that nanoscale electrodes may help meet this challenge. First, nanoscale electrodes were shown to enable intracellular access. Second, because their size scale is within the normal reach of the standard top-down fabrication, the nanoelectrodes can be scaled into a large array for parallelization. Third, such a nanoelectrode array can be monolithically integrated with complementary metal-oxide semiconductor (CMOS) electronics to facilitate the large array operation and the recording of the signals from a massive number of cells. These are some of the central ideas that have motivated the research activity into nanoelectrode electrophysiology, and these past years have seen fruitful developments. This Account aims to synthesize these findings so as to provide a useful reference. Summing up from the recent studies, we will first elucidate the morphology and associated electrical properties of the interface between a nanoelectrode and a cellular membrane

  6. Exact and Approximate Stochastic Simulation of Intracellular Calcium Dynamics

    Nicolas Wieder

    2011-01-01

    pathways. The purpose of the present paper is to provide an overview of the aforementioned simulation approaches and their mutual relationships in the spectrum ranging from stochastic to deterministic algorithms.

  7. Fast tomosynthesis

    Klotz, E.; Linde, R.; Tiemens, U.; Weiss, H.

    1978-01-01

    A system has been constructed for fast tomosynthesis, whereby X-ray photographs are made of a single layer of an object. Twenty five X-ray tubes illuminate the object simultaneously at different angles. The resulting coded image is decoded by projecting it with a pattern of lenses that have the same form as the pattern of X-ray tubes. The coded image is optically correlated with the pattern of the sources. The scale of this can be adjusted so that the desired layer of the object is portrayed. Experimental results of its use in a hospital are presented. (C.F.)

  8. Contribution to the study of liquid-liquid extraction dynamics in the case of fast transfers. Extractions of uranium, plutonium and neptunium in a laboratory centrifugal extractor

    Bergeonneau, Philippe

    1978-01-01

    The liquid-liquid extraction (also named solvent-based extraction) is a very important technique for the reprocessing of irradiated nuclear fuels. This research thesis is based on the use of a laboratory centrifugal extractor which allows interesting conditions to be achieved: fast transfer due to an intense solution mixing, very short duration of contact between solutions. Thus, after a report of a bibliographical study on chemical mechanisms of extraction, on the composition of extracted species, on extraction kinetics, and on centrifugal extractors, this thesis reports the design, fabrication and use of a centrifugal extractor: presentation of fundamental principles, description and characteristics (materials, hydrodynamic operation test and problems, prototype). It reports studies of fast transfer kinetics: mathematical processing, result interpretation, results and discussions of extraction kinetics for nitric acid, uranium VI and IV, plutonium IV, neptunium IV, and comparison of the different extraction kinetics

  9. Modeling nanoparticle uptake and intracellular distribution using stochastic process algebras

    Dobay, M. P. D., E-mail: maria.pamela.david@physik.uni-muenchen.de; Alberola, A. Piera; Mendoza, E. R.; Raedler, J. O., E-mail: joachim.raedler@physik.uni-muenchen.de [Ludwig-Maximilians University, Faculty of Physics, Center for NanoScience (Germany)

    2012-03-15

    Computational modeling is increasingly important to help understand the interaction and movement of nanoparticles (NPs) within living cells, and to come to terms with the wealth of data that microscopy imaging yields. A quantitative description of the spatio-temporal distribution of NPs inside cells; however, it is challenging due to the complexity of multiple compartments such as endosomes and nuclei, which themselves are dynamic and can undergo fusion and fission and exchange their content. Here, we show that stochastic pi calculus, a widely-used process algebra, is well suited for mapping surface and intracellular NP interactions and distributions. In stochastic pi calculus, each NP is represented as a process, which can adopt various states such as bound or aggregated, as well as be passed between processes representing location, as a function of predefined stochastic channels. We created a pi calculus model of gold NP uptake and intracellular movement and compared the evolution of surface-bound, cytosolic, endosomal, and nuclear NP densities with electron microscopy data. We demonstrate that the computational approach can be extended to include specific molecular binding and potential interaction with signaling cascades as characteristic for NP-cell interactions in a wide range of applications such as nanotoxicity, viral infection, and drug delivery.

  10. Modeling nanoparticle uptake and intracellular distribution using stochastic process algebras

    Dobay, M. P. D.; Alberola, A. Piera; Mendoza, E. R.; Rädler, J. O.

    2012-01-01

    Computational modeling is increasingly important to help understand the interaction and movement of nanoparticles (NPs) within living cells, and to come to terms with the wealth of data that microscopy imaging yields. A quantitative description of the spatio-temporal distribution of NPs inside cells; however, it is challenging due to the complexity of multiple compartments such as endosomes and nuclei, which themselves are dynamic and can undergo fusion and fission and exchange their content. Here, we show that stochastic pi calculus, a widely-used process algebra, is well suited for mapping surface and intracellular NP interactions and distributions. In stochastic pi calculus, each NP is represented as a process, which can adopt various states such as bound or aggregated, as well as be passed between processes representing location, as a function of predefined stochastic channels. We created a pi calculus model of gold NP uptake and intracellular movement and compared the evolution of surface-bound, cytosolic, endosomal, and nuclear NP densities with electron microscopy data. We demonstrate that the computational approach can be extended to include specific molecular binding and potential interaction with signaling cascades as characteristic for NP-cell interactions in a wide range of applications such as nanotoxicity, viral infection, and drug delivery.

  11. Modeling nanoparticle uptake and intracellular distribution using stochastic process algebras

    Dobay, M. P. D.; Alberola, A. Piera; Mendoza, E. R.; Rädler, J. O.

    2012-03-01

    Computational modeling is increasingly important to help understand the interaction and movement of nanoparticles (NPs) within living cells, and to come to terms with the wealth of data that microscopy imaging yields. A quantitative description of the spatio-temporal distribution of NPs inside cells; however, it is challenging due to the complexity of multiple compartments such as endosomes and nuclei, which themselves are dynamic and can undergo fusion and fission and exchange their content. Here, we show that stochastic pi calculus, a widely-used process algebra, is well suited for mapping surface and intracellular NP interactions and distributions. In stochastic pi calculus, each NP is represented as a process, which can adopt various states such as bound or aggregated, as well as be passed between processes representing location, as a function of predefined stochastic channels. We created a pi calculus model of gold NP uptake and intracellular movement and compared the evolution of surface-bound, cytosolic, endosomal, and nuclear NP densities with electron microscopy data. We demonstrate that the computational approach can be extended to include specific molecular binding and potential interaction with signaling cascades as characteristic for NP-cell interactions in a wide range of applications such as nanotoxicity, viral infection, and drug delivery.

  12. Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

    Appert-Rolland, C.; Ebbinghaus, M.; Santen, L.

    2015-09-01

    Cells are the elementary units of living organisms, which are able to carry out many vital functions. These functions rely on active processes on a microscopic scale. Therefore, they are strongly out-of-equilibrium systems, which are driven by continuous energy supply. The tasks that have to be performed in order to maintain the cell alive require transportation of various ingredients, some being small, others being large. Intracellular transport processes are able to induce concentration gradients and to carry objects to specific targets. These processes cannot be carried out only by diffusion, as cells may be crowded, and quite elongated on molecular scales. Therefore active transport has to be organized. The cytoskeleton, which is composed of three types of filaments (microtubules, actin and intermediate filaments), determines the shape of the cell, and plays a role in cell motion. It also serves as a road network for a special kind of vehicles, namely the cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach. It is a central issue to understand how intracellular transport driven by molecular motors is regulated. The interest for this type of question was enhanced when it was discovered that intracellular transport breakdown is one of the signatures of some neuronal diseases like the Alzheimer. We give a survey of the current knowledge on microtubule based intracellular transport. Our review includes on the one hand an overview of biological facts, obtained from experiments, and on the other hand a presentation of some modeling attempts based on cellular automata. We present some background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the

  13. Leishmania hijacking of the macrophage intracellular compartments.

    Liévin-Le Moal, Vanessa; Loiseau, Philippe M

    2016-02-01

    Leishmania spp., transmitted to humans by the bite of the sandfly vector, are responsible for the three major forms of leishmaniasis, cutaneous, diffuse mucocutaneous and visceral. Leishmania spp. interact with membrane receptors of neutrophils and macrophages. In macrophages, the parasite is internalized within a parasitophorous vacuole and engages in a particular intracellular lifestyle in which the flagellated, motile Leishmania promastigote metacyclic form differentiates into non-motile, metacyclic amastigote form. This phenomenon is induced by Leishmania-triggered events leading to the fusion of the parasitophorous vacuole with vesicular members of the host cell endocytic pathway including recycling endosomes, late endosomes and the endoplasmic reticulum. Maturation of the parasitophorous vacuole leads to the intracellular proliferation of the Leishmania amastigote forms by acquisition of host cell nutrients while escaping host defense responses. © 2015 FEBS.

  14. Reduction of intracellular glutathione content and radiosensitivity

    Vos, O.; Schans, G.P. van der; Roos-Verheij, W.S.D.

    1986-05-01

    The intracellular glutathione (GSH) content in HeLa, CHO and V79 cells was reduced by incubating the cells in growth medium containing buthionine sulfoximine (BSO) or diethyl maleate (DEM). Clonogenicity, single strand DNA breaks (ssb) and double strand DNA breaks (dsb) were used as criteria for radiation induced damage after X- or γ irradiation. In survival experiments DEM gave a slightly larger sensitization although it gave a smaller reduction of the intracellular GSH. In general, sensitization was larger for dsb than for ssb, also the reduction of the OER was generally larger for dsb than for ssb. This may be due to the higher dose rate in case of dsb experiments resulting in a higher rate of radiochemical oxygen consumption. In general, no effect was found on post-irradiation repair of ssb and dsb. (Auth.)

  15. Reduction of intracellular glutathione content and radiosensitivity

    Vos, O.; Schans, G.P. van der; Roos-Verheij, W.S.D.

    1986-01-01

    The intracellular glutathione (GSH) content of HeLa, CHO and V79 cells was reduced by incubating the cells in growth medium containing buthionine sulphoximine or diethyl maleate (DEM). Clonogenicity, single-strand DNA breaks (ssb) and double-strand DNA breaks (dsb) were used as criteria for radiation-induced damage after X- or γ-irradiation. In survival experiments, DEM gave a slightly larger sensitization although it gave a smaller reduction of the intracellular GSH. In general, sensitization was larger for dsb than for ssb, also the reduction of the o.e.r. was generally larger for dsb than for ssb. This may be due to the higher dose rate in case of dsb experiments resulting in a higher rate of radiochemical oxygen consumption. In general, no effect was found on post-irradiation repair of ssb and dsb. (author)

  16. Intracellular mechanisms of solar water disinfection

    Castro-Alférez, María; Polo-López, María Inmaculada; Fernández-Ibáñez, Pilar

    2016-12-01

    Solar water disinfection (SODIS) is a zero-cost intervention measure to disinfect drinking water in areas of poor access to improved water sources, used by more than 6 million people in the world. The bactericidal action of solar radiation in water has been widely proven, nevertheless the causes for this remain still unclear. Scientific literature points out that generation of reactive oxygen species (ROS) inside microorganisms promoted by solar light absorption is the main reason. For the first time, this work reports on the experimental measurement of accumulated intracellular ROS in E. coli during solar irradiation. For this experimental achievement, a modified protocol based on the fluorescent probe dichlorodihydrofluorescein diacetate (DCFH-DA), widely used for oxidative stress in eukaryotic cells, has been tested and validated for E. coli. Our results demonstrate that ROS and their accumulated oxidative damages at intracellular level are key in solar water disinfection.

  17. Intracellular serpins, firewalls and tissue necrosis.

    Marciniak, Stefan J; Lomas, David A

    2008-02-01

    Luke and colleagues have recently attributed a new role to a member of the serpin superfamily of serine proteinase inhibitors. They have used Caenorhabditis elegans to show that an intracellular serpin is crucial for maintaining lysosomal integrity. We examine the role of this firewall in preventing necrosis and attempt to integrate this with current theories of stress-induced protein degradation. We discuss how mutant serpins cause disease either through polymerization or now, perhaps, by unleashing necrosis.

  18. Fluorescent nanoparticles for intracellular sensing: A review

    Ruedas-Rama, Maria J.; Walters, Jamie D.; Orte, Angel; Hall, Elizabeth A.H.

    2012-01-01

    Highlights: ► Analytical applications of fluorescent nanoparticles (NPs) in intracellular sensing. ► Critical review on performance of QDots, metal NPs, silica NPs, and polymer NPs. ► Highlighted potential of fluorescence lifetime imaging microscopy (FLIM). - Abstract: Fluorescent nanoparticles (NPs), including semiconductor NPs (Quantum Dots), metal NPs, silica NPs, polymer NPs, etc., have been a major focus of research and development during the past decade. The fluorescent nanoparticles show unique chemical and optical properties, such as brighter fluorescence, higher photostability and higher biocompatibility, compared to classical fluorescent organic dyes. Moreover, the nanoparticles can also act as multivalent scaffolds for the realization of supramolecular assemblies, since their high surface to volume ratio allow distinct spatial domains to be functionalized, which can provide a versatile synthetic platform for the implementation of different sensing schemes. Their excellent properties make them one of the most useful tools that chemistry has supplied to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In this review, we focus on the developments and analytical applications of fluorescent nanoparticles in chemical and biological sensing within the intracellular environment. The review also points out the great potential of fluorescent NPs for fluorescence lifetime imaging microscopy (FLIM). Finally, we also give an overview of the current methods for delivering of fluorescent NPs into cells, where critically examine the benefits and liabilities of each strategy.

  19. Fluorescent nanoparticles for intracellular sensing: A review

    Ruedas-Rama, Maria J., E-mail: mjruedas@ugr.esmailto [Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, Campus Cartuja, 18071, Granada (Spain); Walters, Jamie D. [Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, UK CB2 1QT (United Kingdom); Orte, Angel [Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, Campus Cartuja, 18071, Granada (Spain); Hall, Elizabeth A.H., E-mail: lisa.hall@biotech.cam.ac.uk [Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QT (United Kingdom)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer Analytical applications of fluorescent nanoparticles (NPs) in intracellular sensing. Black-Right-Pointing-Pointer Critical review on performance of QDots, metal NPs, silica NPs, and polymer NPs. Black-Right-Pointing-Pointer Highlighted potential of fluorescence lifetime imaging microscopy (FLIM). - Abstract: Fluorescent nanoparticles (NPs), including semiconductor NPs (Quantum Dots), metal NPs, silica NPs, polymer NPs, etc., have been a major focus of research and development during the past decade. The fluorescent nanoparticles show unique chemical and optical properties, such as brighter fluorescence, higher photostability and higher biocompatibility, compared to classical fluorescent organic dyes. Moreover, the nanoparticles can also act as multivalent scaffolds for the realization of supramolecular assemblies, since their high surface to volume ratio allow distinct spatial domains to be functionalized, which can provide a versatile synthetic platform for the implementation of different sensing schemes. Their excellent properties make them one of the most useful tools that chemistry has supplied to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In this review, we focus on the developments and analytical applications of fluorescent nanoparticles in chemical and biological sensing within the intracellular environment. The review also points out the great potential of fluorescent NPs for fluorescence lifetime imaging microscopy (FLIM). Finally, we also give an overview of the current methods for delivering of fluorescent NPs into cells, where critically examine the benefits and liabilities of each strategy.

  20. Intracellular Cholesterol Trafficking and Impact in Neurodegeneration

    Fabian Arenas

    2017-11-01

    Full Text Available Cholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhibits a heterogeneous regulation in distinct brain cell populations. Due to the key role of cholesterol in brain physiology and function, alterations in cholesterol homeostasis and levels have been linked to brain diseases and neurodegeneration. In the case of Alzheimer disease (AD, however, this association remains unclear with evidence indicating that either increased or decreased total brain cholesterol levels contribute to this major neurodegenerative disease. Here, rather than analyzing the role of total cholesterol levels in neurodegeneration, we focus on the contribution of intracellular cholesterol pools, particularly in endolysosomes and mitochondria through its trafficking via specialized membrane domains delineated by the contacts between endoplasmic reticulum and mitochondria, in the onset of prevalent neurodegenerative diseases such as AD, Parkinson disease, and Huntington disease as well as in lysosomal disorders like Niemann-Pick type C disease. We dissect molecular events associated with intracellular cholesterol accumulation, especially in mitochondria, an event that results in impaired mitochondrial antioxidant defense and function. A better understanding of the mechanisms involved in the distribution of cholesterol in intracellular compartments may shed light on the role of cholesterol homeostasis disruption in neurodegeneration and may pave the way for specific intervention opportunities.

  1. A bacteriophage endolysin that eliminates intracellular streptococci

    Shen, Yang; Barros, Marilia; Vennemann, Tarek; Gallagher, D Travis; Yin, Yizhou; Linden, Sara B; Heselpoth, Ryan D; Spencer, Dennis J; Donovan, David M; Moult, John; Fischetti, Vincent A; Heinrich, Frank; Lösche, Mathias; Nelson, Daniel C

    2016-01-01

    PlyC, a bacteriophage-encoded endolysin, lyses Streptococcus pyogenes (Spy) on contact. Here, we demonstrate that PlyC is a potent agent for controlling intracellular Spy that often underlies refractory infections. We show that the PlyC holoenzyme, mediated by its PlyCB subunit, crosses epithelial cell membranes and clears intracellular Spy in a dose-dependent manner. Quantitative studies using model membranes establish that PlyCB interacts strongly with phosphatidylserine (PS), whereas its interaction with other lipids is weak, suggesting specificity for PS as its cellular receptor. Neutron reflection further substantiates that PlyC penetrates bilayers above a PS threshold concentration. Crystallography and docking studies identify key residues that mediate PlyCB–PS interactions, which are validated by site-directed mutagenesis. This is the first report that a native endolysin can traverse epithelial membranes, thus substantiating the potential of PlyC as an antimicrobial for Spy in the extracellular and intracellular milieu and as a scaffold for engineering other functionalities. DOI: http://dx.doi.org/10.7554/eLife.13152.001 PMID:26978792

  2. Fast Swinnex Filtration (FSF): A fast and robust sampling and extraction method suitable for metabolomics analysis of cultures grown in complex media

    McCloskey, Douglas; Utrilla, Jose; Naviaux, Robert K.

    2015-01-01

    , we develop a fast-filtration method using pressuredriven Swinnex filters. We show that the method is fast enough to provide an accurate snapshot of intracellular metabolism, reduces matrix interference from the media to improve the number of compounds that can be detected, and is applicable...... to anaerobic and aerobic liquid cultures grown in a variety of culturing systems. Furthermore, we apply the fast filtration method to investigate differences in the absolute intracellular metabolite levels of anaerobic cultures grown in minimal and complex media....

  3. Ultra-fast charge carrier dynamics across the spectrum of an optical gain media based on InAs/AlGaInAs/InP quantum dots

    I. Khanonkin

    2017-03-01

    Full Text Available The charge carrier dynamics of improved InP-based InAs/AlGaInAs quantum dot (QD semiconductor optical amplifiers are examined employing the multi-wavelength ultrafast pump-probe measurement technique. The transient transmission response of the continuous wave probe shows interesting dynamical processes during the initial 2-3 ps after the pump pulse, when carriers originating from two photon absorption contribute the least to the recovery. The effects of optical excitations and electrical bias levels on the recovery dynamics of the gain in energetically different QDs are quantified and discussed. The experimental observations are validated qualitatively using a comprehensive finite-difference time-domain model by recording the time evolution of the charge carriers in the QDs ensemble following the pulse.

  4. Calcium dynamics in vascular smooth muscle

    Amberg, Gregory C.; Navedo, Manuel F.

    2013-01-01

    Smooth muscle cells are ultimately responsible for determining vascular luminal diameter and blood flow. Dynamic changes in intracellular calcium are a critical mechanism regulating vascular smooth muscle contractility. Processes influencing intracellular calcium are therefore important regulators of vascular function with physiological and pathophysiological consequences. In this review we discuss the major dynamic calcium signals identified and characterized in vascular smooth muscle cells....

  5. Open LED Illuminator: A Simple and Inexpensive LED Illuminator for Fast Multicolor Particle Tracking in Neurons

    Bosse, Jens B.; Tanneti, Nikhila S.; Hogue, Ian B.; Enquist, Lynn W.

    2015-01-01

    Dual-color live cell fluorescence microscopy of fast intracellular trafficking processes, such as axonal transport, requires rapid switching of illumination channels. Typical broad-spectrum sources necessitate the use of mechanical filter switching, which introduces delays between acquisition of different fluorescence channels, impeding the interpretation and quantification of highly dynamic processes. Light Emitting Diodes (LEDs), however, allow modulation of excitation light in microseconds. Here we provide a step-by-step protocol to enable any scientist to build a research-grade LED illuminator for live cell microscopy, even without prior experience with electronics or optics. We quantify and compare components, discuss our design considerations, and demonstrate the performance of our LED illuminator by imaging axonal transport of herpes virus particles with high temporal resolution. PMID:26600461

  6. Open LED Illuminator: A Simple and Inexpensive LED Illuminator for Fast Multicolor Particle Tracking in Neurons.

    Jens B Bosse

    Full Text Available Dual-color live cell fluorescence microscopy of fast intracellular trafficking processes, such as axonal transport, requires rapid switching of illumination channels. Typical broad-spectrum sources necessitate the use of mechanical filter switching, which introduces delays between acquisition of different fluorescence channels, impeding the interpretation and quantification of highly dynamic processes. Light Emitting Diodes (LEDs, however, allow modulation of excitation light in microseconds. Here we provide a step-by-step protocol to enable any scientist to build a research-grade LED illuminator for live cell microscopy, even without prior experience with electronics or optics. We quantify and compare components, discuss our design considerations, and demonstrate the performance of our LED illuminator by imaging axonal transport of herpes virus particles with high temporal resolution.

  7. Towards transparent all-optical label-swapped networks: 40 Gbit/s ultra-fast dynamic wavelength routing using integrated devices

    Seoane, Jorge; Holm-Nielsen, Pablo Villanueva; Jeppesen, Palle

    2006-01-01

    All-optical routing of 40 Gbit/s 1.6 ns packets is demonstrated employing integrated devices based on SOA-MZIs. The scheme allows wavelength transparent operation and sub-nanosecond dynamic wavelength selection for future packet/label switched networks....

  8. Dynamics of Change in Human-Driven and Natural Systems: Fast Forward, Slow Motion, Same Movie? A Case Study from Plant Protection

    Didier Andrivon

    2012-03-01

    Full Text Available Evolutionary biology and evolutionary ecology deal with change in species and ecosystems over time, and propose mechanisms to explain and predict these. In particular, they look for generic elements that will drive any organism or phylum to adaptive changes or to extinction. This paper, using examples from the field of plant protection against pests and diseases, shows that the patterns of change observed in natural and in human-driven systems are comparable, and proposes that their similarities result from the same mechanisms operating at different paces. Human-driven systems can thus be seen simply as ‘fast-forward’ versions of natural systems, making them tractable tools to test and predict elements from evolutionary theory. Conversely, the convergence between natural and human-driven systems opens opportunities for a more widespread use of evolutionary theory when analyzing and optimizing any human-driven system, or predicting its adaptability to changing conditions.

  9. Fast Shepard interpolation on graphics processing units: potential energy surfaces and dynamics for H + CH4 → H2 + CH3.

    Welsch, Ralph; Manthe, Uwe

    2013-04-28

    A strategy for the fast evaluation of Shepard interpolated potential energy surfaces (PESs) utilizing graphics processing units (GPUs) is presented. Speed ups of several orders of magnitude are gained for the title reaction on the ZFWCZ PES [Y. Zhou, B. Fu, C. Wang, M. A. Collins, and D. H. Zhang, J. Chem. Phys. 134, 064323 (2011)]. Thermal rate constants are calculated employing the quantum transition state concept and the multi-layer multi-configurational time-dependent Hartree approach. Results for the ZFWCZ PES are compared to rate constants obtained for other ab initio PESs and problems are discussed. A revised PES is presented. Thermal rate constants obtained for the revised PES indicate that an accurate description of the anharmonicity around the transition state is crucial.

  10. Fast breeder reactor research

    1975-01-01

    Full text: The meeting was attended by 15 participants from seven countries and two international organizations. The Eighth Annual Meeting of the International Working Group on Fast Reactors (IWGFR) was attended by representatives from France, Fed. Rep. Germany, Italy, Japan, United Kingdom, Union of Soviet Socialist Republics and the United States of America - countries that have made significant progress in developing the technology and physics of sodium cooled fast reactors and have extensive national programmes in this field - as well as by representatives of the Commission of the European Communities and the IAEA. The design of fast-reactor power plants is a more difficult task than developing facilities with thermal reactors. Different reactor kinetics and dynamics, a hard neutron spectrum, larger integral doses of fuel and structural material irradiation, higher core temperatures, the use of an essentially novel coolant, and, as a result of all these factors, the additional reliability and safety requirements that are imposed on the planning and operation of sodium cooled fast reactors - all these factors pose problems that can be solved comprehensively only by countries with a high level of scientific and technical development. The exchange of experience between these countries and their combined efforts in solving the fundamental problems that arise in planning, constructing and operating fast reactors are promoting technical progress and reducing the relative expenditure required for various studies on developing and introducing commercial fast reactors. For this reason, the meeting concentrated on reviewing and discussing national fast reactor programmes. The situation with regard to planning, constructing and operating fast experimental and demonstration reactors in the countries concerned, the experience accumulated in operating them, the difficulties arising during operation and ways of over-coming them, the search for optimal designs for the power

  11. Quantitative quenching evaluation and direct intracellular metabolite analysis in Penicillium chrysogenum.

    Meinert, Sabine; Rapp, Sina; Schmitz, Katja; Noack, Stephan; Kornfeld, Georg; Hardiman, Timo

    2013-07-01

    Sustained progress in metabolic engineering methodologies has stimulated new efforts toward optimizing fungal production strains such as through metabolite analysis of Penicillium chrysogenum industrial-scale processes. Accurate intracellular metabolite quantification requires sampling procedures that rapidly stop metabolism (quenching) and avoid metabolite loss via the cell membrane (leakage). When sampling protocols are validated, the quenching efficiency is generally not quantitatively assessed. For fungal metabolomics, quantitative biomass separation using centrifugation is a further challenge. In this study, P. chrysogenum intracellular metabolites were quantified directly from biomass extracts using automated sampling and fast filtration. A master/slave bioreactor concept was applied to provide industrial production conditions. Metabolic activity during sampling was monitored by 13C tracing. Enzyme activities were efficiently stopped and metabolite leakage was absent. This work provides a reliable method for P. chrysogenum metabolomics and will be an essential base for metabolic engineering of industrial processes. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. RhoA, Rho kinase, JAK2, and STAT3 may be the intracellular determinants of longevity implicated in the progeric influence of obesity: Insulin, IGF-1, and leptin may all conspire to promote stem cell exhaustion.

    Tapia, Patrick C

    2006-01-01

    seen with the inexorable passage of time. Besides the obvious utility for the management for human age-related dysfunction that investigation of pharmacologic inhibitors of these proteins would provide, interventions such as caloric restriction and possibly intermittent fasting may beneficially influence stem cell proliferation dynamics and reduce intracellular correlates of mitogenic drive. Integrating the findings present in the present body of research may reveal endocrinological states that are compatible with longevity, and will also provide novel insight into the specific proteomic determinants of age-related physiologic decline, ushering in a new epoch of medicine that fosters the management of the "pre-etiopathology" of chronic disease and disability of aging, therefore mitigating the suffering widely thought to be inherent in the latter stages of life.

  13. Azithromycin effectiveness against intracellular infections of Francisella

    Mann Barbara J

    2010-04-01

    Full Text Available Abstract Background Macrolide antibiotics are commonly administered for bacterial respiratory illnesses. Azithromycin (Az is especially noted for extremely high intracellular concentrations achieved within macrophages which is far greater than the serum concentration. Clinical strains of Type B Francisella (F. tularensis have been reported to be resistant to Az, however our laboratory Francisella strains were found to be sensitive. We hypothesized that different strains/species of Francisella (including Type A may have different susceptibilities to Az, a widely used and well-tolerated antibiotic. Results In vitro susceptibility testing of Az confirmed that F. tularensis subsp. holarctica Live Vaccine Strain (LVS (Type B was not sensitive while F. philomiragia, F. novicida, and Type A F. tularensis (NIH B38 and Schu S4 strain were susceptible. In J774A.1 mouse macrophage cells infected with F. philomiragia, F. novicida, and F. tularensis LVS, 5 μg/ml Az applied extracellularly eliminated intracellular Francisella infections. A concentration of 25 μg/ml Az was required for Francisella-infected A549 human lung epithelial cells, suggesting that macrophages are more effective at concentrating Az than epithelial cells. Mutants of RND efflux components (tolC and ftlC in F. novicida demonstrated less sensitivity to Az by MIC than the parental strain, but the tolC disc-inhibition assay demonstrated increased sensitivity, indicating a complex role for the outer-membrane transporter. Mutants of acrA and acrB mutants were less sensitive to Az than the parental strain, suggesting that AcrAB is not critical for the efflux of Az in F. novicida. In contrast, F. tularensis Schu S4 mutants ΔacrB and ΔacrA were more sensitive than the parental strain, indicating that the AcrAB may be important for Az efflux in F. tularensis Schu S4. F. novicida LPS O-antigen mutants (wbtN, wbtE, wbtQ and wbtA were found to be less sensitive in vitro to Az compared to the wild

  14. Fast Convolution Module (Fast Convolution Module)

    Bierens, L

    1997-01-01

    This report describes the design and realisation of a real-time range azimuth compression module, the so-called 'Fast Convolution Module', based on the fast convolution algorithm developed at TNO-FEL...

  15. Invited article: The fast readout low noise camera as a versatile x-ray detector for time resolved dispersive extended x-ray absorption fine structure and diffraction studies of dynamic problems in materials science, chemistry, and catalysis

    Labiche, Jean-Claude; Mathon, Olivier; Pascarelli, Sakura; Newton, Mark A.; Ferre, Gemma Guilera; Curfs, Caroline; Vaughan, Gavin; Homs, Alejandro; Carreiras, David Fernandez

    2007-01-01

    Originally conceived and developed at the European Synchrotron Radiation Facility (ESRF) as an 'area' detector for rapid x-ray imaging studies, the fast readout low noise (FReLoN) detector of the ESRF [J.-C. Labiche, ESRF Newsletter 25, 41 (1996)] has been demonstrated to be a highly versatile and unique detector. Charge coupled device (CCD) cameras at present available on the public market offer either a high dynamic range or a high readout speed. A compromise between signal dynamic range and readout speed is always sought. The parameters of the commercial cameras can sometimes be tuned, in order to better fulfill the needs of specific experiments, but in general these cameras have a poor duty cycle (i.e., the signal integration time is much smaller than the readout time). In order to address scientific problems such as time resolved experiments at the ESRF, a FReLoN camera has been developed by the Instrument Support Group at ESRF. This camera is a low noise CCD camera that combines high dynamic range, high readout speed, accuracy, and improved duty cycle in a single image. In this paper, we show its application in a quasi-one-dimensional sense to dynamic problems in materials science, catalysis, and chemistry that require data acquisition on a time scale of milliseconds or a few tens of milliseconds. It is demonstrated that in this mode the FReLoN can be applied equally to the investigation of rapid changes in long range order (via diffraction) and local order (via energy dispersive extended x-ray absorption fine structure) and in situations of x-ray hardness and flux beyond the capacity of other detectors

  16. Intracellular bacteria: the origin of dinoflagellate toxicity.

    Silva, E S

    1990-01-01

    Dinoflagellate blooms of the same species have been registered either as toxic or nontoxic and, in the latter case, toxicity may be of different types. A hypothesis has been formulated according to which the bacteria having in some way taken part in the toxin formation are either inside the dinoflagellate cell or in the nutritive liquid. The presence of intracellular bacteria in those microorganisms has been studied mainly in material from cultures, a few from the sea, and several strains were isolated from different species. Experiments with crossed inoculations have shown that the bacterial strain from Gonyaulax tamarensis caused the cells of some other species to become toxic. From nontoxic clonal cultures of Prorocentrum balticum, Glenodinium foliaceum, and Gyrodinium instriatum, after inoculation of that bacterial strain, cultures were obtained whose cell extracts showed the same kind of toxicity as G. tamarensis. No toxic action could be found in the extracts of the bacterial cells form the assayed strains. The interference of intracellular bacteria in the metabolism of dinoflagellates must be the main cause of their toxicity.

  17. Fluorescent nanoparticles for intracellular sensing: a review.

    Ruedas-Rama, Maria J; Walters, Jamie D; Orte, Angel; Hall, Elizabeth A H

    2012-11-02

    Fluorescent nanoparticles (NPs), including semiconductor NPs (Quantum Dots), metal NPs, silica NPs, polymer NPs, etc., have been a major focus of research and development during the past decade. The fluorescent nanoparticles show unique chemical and optical properties, such as brighter fluorescence, higher photostability and higher biocompatibility, compared to classical fluorescent organic dyes. Moreover, the nanoparticles can also act as multivalent scaffolds for the realization of supramolecular assemblies, since their high surface to volume ratio allow distinct spatial domains to be functionalized, which can provide a versatile synthetic platform for the implementation of different sensing schemes. Their excellent properties make them one of the most useful tools that chemistry has supplied to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In this review, we focus on the developments and analytical applications of fluorescent nanoparticles in chemical and biological sensing within the intracellular environment. The review also points out the great potential of fluorescent NPs for fluorescence lifetime imaging microscopy (FLIM). Finally, we also give an overview of the current methods for delivering of fluorescent NPs into cells, where critically examine the benefits and liabilities of each strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Mechanisms of cellular invasion by intracellular parasites.

    Walker, Dawn M; Oghumu, Steve; Gupta, Gaurav; McGwire, Bradford S; Drew, Mark E; Satoskar, Abhay R

    2014-04-01

    Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.

  19. [Intracellular signaling mechanisms in thyroid cancer].

    Mondragón-Terán, Paul; López-Hernández, Luz Berenice; Gutiérrez-Salinas, José; Suárez-Cuenca, Juan Antonio; Luna-Ceballos, Rosa Isela; Erazo Valle-Solís, Aura

    2016-01-01

    Thyroid cancer is the most common malignancy of the endocrine system, the papillary variant accounts for 80-90% of all diagnosed cases. In the development of papillary thyroid cancer, BRAF and RAS genes are mainly affected, resulting in a modification of the system of intracellular signaling proteins known as «protein kinase mitogen-activated» (MAPK) which consist of «modules» of internal signaling proteins (Receptor/Ras/Raf/MEK/ERK) from the cell membrane to the nucleus. In thyroid cancer, these signanling proteins regulate diverse cellular processes such as differentiation, growth, development and apoptosis. MAPK play an important role in the pathogenesis of thyroid cancer as they are used as molecular biomarkers for diagnostic, prognostic and as possible therapeutic molecular targets. Mutations in BRAF gene have been correlated with poor response to treatment with traditional chemotherapy and as an indicator of poor prognosis. To review the molecular mechanisms involved in intracellular signaling of BRAF and RAS genes in thyroid cancer. Molecular therapy research is in progress for this type of cancer as new molecules have been developed in order to inhibit any of the components of the signaling pathway (RET/PTC)/Ras/Raf/MEK/ERK; with special emphasis on the (RET/PTC)/Ras/Raf section, which is a major effector of ERK pathway. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  20. Enlightening intracellular complexity of living cells with quantitative phase microscopy

    Martinez Torres, C.; Laperrousaz, B.; Berguiga, L.; Boyer Provera, E.; Elezgaray, J.; Nicolini, F. E.; Maguer-Satta, V.; Arneodo, A.; Argoul, F.

    2016-03-01

    The internal distribution of refractive indices (RIs) of a living cell is much more complex than usually admitted in multi-shell models. The reconstruction of RI maps from single phase images has rarely been achieved for several reasons: (i) we still have very little knowledge of the impact of internal macromolecular complexes on the local RI and (ii) phase changes produced by light propagation through the sample are mixed with diffraction effects by internal cell bodies. We propose the implementation a 2D wavelet-based contour chain detection method to distinguish internal boundaries thanks to their greatest optical path difference gradients. These contour chains correspond to the highest image phase contrast and follow the local RI inhomogeneities linked to the intracellular structural intricacy. Their statistics and spatial distribution are morphological indicators for distinguishing cells of different origins and to follow their transformation in pathologic situations. We use this method to compare non adherent blood cells from primary and laboratory culture origins, in healthy and pathological situations (chronic myelogenous leukaemia). In a second part of this presentation, we concentrate on the temporal dynamics of the phase contour chains and we discuss the spectral decomposition of their dynamics in both health and disease.

  1. KrioBlast TM as a New Technology of Hyper-fast Cryopreservation of Cells and Tissues. Part I. Thermodynamic Aspects and Potential Applications in Reproductive and Regenerative Medicine.

    Katkov, I I; Bolyukh, V F; Sukhikh, G T

    2018-03-01

    Kinetic (dynamic) vitrification is a promising trend in cryopreservation of biological materials because it allows avoiding the formation of lethal intracellular ice and minimizes harmful effects of highly toxic penetrating cryoprotectants. A uniform cooling protocol and the same instruments can be used for practically all types of cells. In modern technologies, the rate of cooling is essentially limited by the Leidenfrost effect. We describe a novel platform for kinetic vitrification of biological materials KrioBlast TM that realizes hyper-fast cooling and allows overcoming the Leidenfrost effect. This opens prospects for creation of a novel technology of cell cryopreservation for reproductive and regenerative medicine.

  2. Automatic flow-through dynamic extraction: A fast tool to evaluate char-based remediation of multi-element contaminated mine soils.

    Rosende, María; Beesley, Luke; Moreno-Jimenez, Eduardo; Miró, Manuel

    2016-02-01

    An automatic in-vitro bioaccessibility test based upon dynamic microcolumn extraction in a programmable flow setup is herein proposed as a screening tool to evaluate bio-char based remediation of mine soils contaminated with trace elements as a compelling alternative to conventional phyto-availability tests. The feasibility of the proposed system was evaluated by extracting the readily bioaccessible pools of As, Pb and Zn in two contaminated mine soils before and after the addition of two biochars (9% (w:w)) of diverse source origin (pine and olive). Bioaccessible fractions under worst-case scenarios were measured using 0.001 mol L(-1) CaCl2 as extractant for mimicking plant uptake, and analysis of the extracts by inductively coupled optical emission spectrometry. The t-test of comparison of means revealed an efficient metal (mostly Pb and Zn) immobilization by the action of olive pruning-based biochar against the bare (control) soil at the 0.05 significance level. In-vitro flow-through bioaccessibility tests are compared for the first time with in-vivo phyto-toxicity assays in a microcosm soil study. By assessing seed germination and shoot elongation of Lolium perenne in contaminated soils with and without biochar amendments the dynamic flow-based bioaccessibility data proved to be in good agreement with the phyto-availability tests. Experimental results indicate that the dynamic extraction method is a viable and economical in-vitro tool in risk assessment explorations to evaluate the feasibility of a given biochar amendment for revegetation and remediation of metal contaminated soils in a mere 10 min against 4 days in case of phyto-toxicity assays. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Lanthanide paramagnetic probes for NMR spectroscopic studies of fast molecular conformational dynamics and temperature control. Effective six-site proton exchange in 18-crown-6 by exchange spectroscopy.

    Babailov, Sergey P

    2012-02-06

    (1)H and (13)C NMR measurements are reported for the CDCl(3) and CD(2)Cl(2) solutions of [La(18-crown-6)(NO(3))(3)] (I), [Pr(18-crown-6) (NO(3))(3)] (II), [Ce(18-crown-6)(NO(3))(3)] (III), and [Nd(18-crown-6)(NO(3))(3)] (IV) complexes. Temperature dependencies of the (1)H NMR spectra of paramagnetic II-IV have been analyzed using the dynamic NMR (DNMR) methods for six-site exchange. Two types of conformational dynamic processes were identified (the first one is conditioned by interconversion of complex enantiomeric forms and pseudorotation of a macrocycle molecule upon the C(2) symmetry axis; the second one is conditioned by macrocycle molecule inversion). Application of exchange spectroscopy (2D-EXSY) of DNMR for investigation of this dynamic system (II-IV) simplifies the assignment of the NMR signals and represents the first experimental study of multisite exchange. In the present work, the methodology of paramagnetic 4f (Ce, Pr, and Nd) probe applications for the study of free-energy, enthalpy, and entropy changes in chemical exchange processes, as well as the advantages of this method in a comparison with DNMR studies of diamagnetic substances, is discussed. In particular, as a result of paramagnetic chemical shifts in 4f complexes, the range of measurable rate constants expands considerably compared to the analogous range in diamagnetic compounds. Coordination compounds investigated in the paper represent new types of thermometric NMR sensors and lanthanide paramagnetic probes for in situ temperature control in solution.

  4. Advance Liquid Metal Reactor Discrete Dynamic Event Tree/Bayesian Network Analysis and Incident Management Guidelines (Risk Management for Sodium Fast Reactors)

    Denman, Matthew R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Groth, Katrina M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Cardoni, Jeffrey N. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wheeler, Timothy A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-04-01

    Accident management is an important component to maintaining risk at acceptable levels for all complex systems, such as nuclear power plants. With the introduction of self-correcting, or inherently safe, reactor designs the focus has shifted from management by operators to allowing the system's design to manage the accident. Inherently and passively safe designs are laudable, but nonetheless extreme boundary conditions can interfere with the design attributes which facilitate inherent safety, thus resulting in unanticipated and undesirable end states. This report examines an inherently safe and small sodium fast reactor experiencing a beyond design basis seismic event with the intend of exploring two issues : (1) can human intervention either improve or worsen the potential end states and (2) can a Bayesian Network be constructed to infer the state of the reactor to inform (1). ACKNOWLEDGEMENTS The authors would like to acknowledge the U.S. Department of Energy's Office of Nuclear Energy for funding this research through Work Package SR-14SN100303 under the Advanced Reactor Concepts program. The authors also acknowledge the PRA teams at Argonne National Laboratory, Oak Ridge National Laboratory, and Idaho National Laboratory for their continue d contributions to the advanced reactor PRA mission area.

  5. Population dynamics of the fast-growing sub-populations of Pseudomonas and total bacteria, and their protozoan grazers, revealed by fenpropimorph treatment

    Thirup, L; Ekelund, Flemming; Johnsen, Kaare Eske

    2000-01-01

    The population dynamics of indigenous soil bacteria and protozoa on decaying barley roots were followed by using litter bags buried in laboratory-incubated soil. The soil was either non-treated or treated with the fungicide fenpropimorph (in the formulation Corbel) at concentrations corresponding...... of protozoa corresponding to the two subpopulations was followed. The results strongly indicate a predatory association between the protozoa and bacteria. This was shown by a tight temporal association, and by a stimulation of bacteria following predatory release when protozoa were inhibited by fenpropimorph...

  6. Weakened Intracellular Zn2+-Buffering in the Aged Dentate Gyrus and Its Involvement in Erasure of Maintained LTP.

    Takeda, Atsushi; Tamano, Haruna; Murakami, Taku; Nakada, Hiroyuki; Minamino, Tatsuya; Koike, Yuta

    2018-05-01

    Memory is lost by the increased influx of extracellular Zn 2+ into neurons. It is possible that intracellular Zn 2+ dynamics is modified even at non-zincergic medial perforant pathway-dentate granule cell synapses along with aging and that vulnerability to the modification is linked to age-related cognitive decline. To examine these possibilities, vulnerability of long-term potentiation (LTP) maintenance, which underlies memory retention, to modification of synaptic Zn 2+ dynamics was compared between young and aged rats. The influx of extracellular Zn 2+ into dentate granule cells was increased in aged rats after injection of high K + into the dentate gyrus, but not in young rats. This increase impaired maintained LTP in aged rats. However, the impairment was rescued by co-injection of CaEDTA, an extracellular Zn 2+ chelator, or CNQX, an AMPA receptor antagonist, which suppressed the Zn 2+ influx. Maintained LTP was also impaired in aged rats after injection of ZnAF-2DA into the dentate gyrus that chelates intracellular Zn 2+ , but not in young rats. Interestingly, the capacity of chelating intracellular Zn 2+ with intracellular ZnAF-2 was almost lost in the aged dentate gyrus 2 h after injection of ZnAF-2DA into the dentate gyrus, suggesting that intracellular Zn 2+ -buffering is weakened in the aged dentate gyrus, compared to the young dentate gyrus. In the dentate gyrus of aged rats, maintained LTP is more vulnerable to modification of intracellular Zn 2+ dynamics than in young rats, probably due to weakened intracellular Zn 2+ -buffering.

  7. FAST: FAST Analysis of Sequences Toolbox

    Travis J. Lawrence

    2015-05-01

    Full Text Available FAST (FAST Analysis of Sequences Toolbox provides simple, powerful open source command-line tools to filter, transform, annotate and analyze biological sequence data. Modeled after the GNU (GNU’s Not Unix Textutils such as grep, cut, and tr, FAST tools such as fasgrep, fascut, and fastr make it easy to rapidly prototype expressive bioinformatic workflows in a compact and generic command vocabulary. Compact combinatorial encoding of data workflows with FAST commands can simplify the documentation and reproducibility of bioinformatic protocols, supporting better transparency in biological data science. Interface self-consistency and conformity with conventions of GNU, Matlab, Perl, BioPerl, R and GenBank help make FAST easy and rewarding to learn. FAST automates numerical, taxonomic, and text-based sorting, selection and transformation of sequence records and alignment sites based on content, index ranges, descriptive tags, annotated features, and in-line calculated analytics, including composition and codon usage. Automated content- and feature-based extraction of sites and support for molecular population genetic statistics makes FAST useful for molecular evolutionary analysis. FAST is portable, easy to install and secure thanks to the relative maturity of its Perl and BioPerl foundations, with stable releases posted to CPAN. Development as well as a publicly accessible Cookbook and Wiki are available on the FAST GitHub repository at https://github.com/tlawrence3/FAST. The default data exchange format in FAST is Multi-FastA (specifically, a restriction of BioPerl FastA format. Sanger and Illumina 1.8+ FastQ formatted files are also supported. FAST makes it easier for non-programmer biologists to interactively investigate and control biological data at the speed of thought.

  8. Improvement of Microgrid Dynamic Performance under Fault Circumstances using ANFIS for Fast Varying Solar Radiation and Fuzzy Logic Controller for Wind System

    Izadbakhsh Maziar

    2014-12-01

    Full Text Available The microgrid (MG technology integrates distributed generations, energy storage elements and loads. In this paper, dynamic performance enhancement of an MG consisting of wind turbine was investigated using permanent magnet synchronous generation (PMSG, photovoltaic (PV, microturbine generation (MTG systems and flywheel under different circumstances. In order to maximize the output of solar arrays, maximum power point tracking (MPPT technique was used by an adaptive neuro-fuzzy inference system (ANFIS; also, control of turbine output power in high speed winds was achieved using pitch angle control technic by fuzzy logic. For tracking the maximum point, the proposed ANFIS was trained by the optimum values. The simulation results showed that the ANFIS controller of grid-connected mode could easily meet the load demand with less fluctuation around the maximum power point. Moreover, pitch angle controller, which was based on fuzzy logic with wind speed and active power as the inputs, could have faster responses, thereby leading to flatter power curves, enhancement of the dynamic performance of wind turbine and prevention of both frazzle and mechanical damages to PMSG. The thorough wind power generation system, PV system, MTG, flywheel and power electronic converter interface were proposed by using Mat-lab/Simulink.

  9. Reversible and Dynamic Fluorescence Imaging of Cellular Redox Self-Regulation Using Fast-Responsive Near-Infrared Ge-Pyronines.

    Nie, Hailiang; Jing, Jing; Tian, Yong; Yang, Wen; Zhang, Rubo; Zhang, Xiaoling

    2016-04-13

    Cellular self-regulation of reactive oxygen species (ROS) stress via glutathione (GSH) antioxidant repair plays a crucial role in maintaining redox balance, which affects various physiological and pathological pathways. In this work, we developed a simple yet effective strategy for reversible, dynamic, and real-time fluorescence imaging of ROS stress and GSH repair, based on novel Ge-pyronine dyes (GePs). Unlike the current O-pyronine (OP) dye, the fluorescence of GePs can be quenched in GSH reduction and then greatly restored by ROS (e.g., ClO(-), ONOO(-), and HO(•)) oxidation because of their unique affinity toward thiols. The "on-off" and "off-on" fluorescence switch can complete in 10 and 20 s, respectively, and exhibit excellent reversibility in vitro and in cells. GePs also show excitation in the long wavelength from the deep-red to near-infrared (NIR) (621-662 nm) region, high fluorescence quantum yield (Φ(fl) = 0.32-0.44) in aqueous media, and excellent cell permeability. Our results demonstrated that GePs can be used for real-time monitoring of the reversible and dynamic interconversion between ROS oxidation and GSH reduction in living cells. GePs might be a useful tool for investigating various redox-related physiological and pathological pathways.

  10. Fast hydrogen elimination from the [Ru(PH3)3(CO)(H)2] and [Ru(PH3)4(H)2] complexes in the first singlet excited states: A diabatic quantum dynamics study

    Vendrell, Oriol; Moreno, Miquel; Lluch, Jose M.

    2004-01-01

    The photodissociation dynamics of [Ru(PH 3 ) 3 (CO)(H) 2 ] and cis-[Ru(PH 3 ) 4 (H) 2 ] is theoretically analyzed in the lowest two excited singlet states. Energies obtained through electronic density functional theory calculations that use the time-dependent formalism are fitted to analytical reduced two-dimensional potential energy surfaces (2D-PES). The metal-H 2 (R) and H-H (r) distances are the variables of these 2D-PES, the rest of the parameters being kept frozen at the values of the minimum energy structure in the ground electronic state. The time evolution in these 2D-PES is exactly followed by means of a fast Fourier transform algorithm applied to solve the time-dependent Schroedinger equation. A simple diabatization scheme is devised to take into account the probability of transitions between both excited states. The quantum dynamics results point out that photoelimination is almost inexistent if the H 2 fragment is to be expelled without further rearrangement of the rest of the complex. Conversely, when the geometries of the complex are optimized by keeping r and R frozen at the hydrogen elimination barrier coordinates, the new 2D-PES so obtained are highly dissociative, the H 2 fragment being expelled in less than 100 fs. Finally the picture of the whole reaction that emerges from our theoretical results is described and the main differences between both complexes are examined

  11. Land Use Dynamics of the Fast-Growing Shanghai Metropolis, China (1979–2008 and its Implications for Land Use and Urban Planning Policy

    Wei-Chun Ma

    2011-01-01

    Full Text Available Through the integrated approach of remote sensing and geographic information system (GIS techniques, four Landsat TM/ETM+ imagery acquired during 1979 and 2008 were used to quantitatively characterize the patterns of land use and land cover change (LULC and urban sprawl in the fast-growing Shanghai Metropolis, China. Results showed that, the urban/built-up area grew on average by 4,242.06 ha yr−1. Bare land grew by 1,594.66 ha yr−1 on average. In contrast, cropland decreased by 3,286.26 ha yr−1 on average, followed by forest and shrub, water, and tidal land, which decreased by 1,331.33 ha yr−1, 903.43 ha yr−1, and 315.72 ha yr−1 on average, respectively. As a result, during 1979 and 2008 approximately 83.83% of the newly urban/built-up land was converted from cropland (67.35%, forest and shrub (9.12%, water (4.80%, and tidal land (2.19%. Another significant change was the continuous increase in regular residents, which played a very important role in contributing to local population growth and increase in urban/built-up land. This can be explained with this city’s huge demand for investment and qualified labor since the latest industrial transformation. Moreover, with a decrease in cropland, the proportion of population engaged in farming decreased 13.84%. Therefore, significant socio-economic transformation occurred, and this would lead to new demand for land resources. However, due to very scarce land resources and overload of population in Shanghai, the drive to achieve economic goals at the loss of cropland, water, and the other lands is not sustainable. Future urban planning policy aiming at ensuring a win-win balance between sustainable land use and economic growth is urgently needed.

  12. Monitoring changes in the intracellular calcium concentration and synaptic efficacy in the mollusc Aplysia.

    Ludwar, Bjoern Ch; Evans, Colin G; Cropper, Elizabeth C

    2012-07-15

    It has been suggested that changes in intracellular calcium mediate the induction of a number of important forms of synaptic plasticity (e.g., homosynaptic facilitation). These hypotheses can be tested by simultaneously monitoring changes in intracellular calcium and alterations in synaptic efficacy. We demonstrate how this can be accomplished by combining calcium imaging with intracellular recording techniques. Our experiments are conducted in a buccal ganglion of the mollusc Aplysia californica. This preparation has a number of experimentally advantageous features: Ganglia can be easily removed from Aplysia and experiments use adult neurons that make normal synaptic connections and have a normal ion channel distribution. Due to the low metabolic rate of the animal and the relatively low temperatures (14-16 °C) that are natural for Aplysia, preparations are stable for long periods of time. To detect changes in intracellular free calcium we will use the cell impermeant version of Calcium Orange which is easily 'loaded' into a neuron via iontophoresis. When this long wavelength fluorescent dye binds to calcium, fluorescence intensity increases. Calcium Orange has fast kinetic properties and, unlike ratiometric dyes (e.g., Fura 2), requires no filter wheel for imaging. It is fairly photo stable and less phototoxic than other dyes (e.g., fluo-3). Like all non-ratiometric dyes, Calcium Orange indicates relative changes in calcium concentration. But, because it is not possible to account for changes in dye concentration due to loading and diffusion, it can not be calibrated to provide absolute calcium concentrations. An upright, fixed stage, compound microscope was used to image neurons with a CCD camera capable of recording around 30 frames per second. In Aplysia this temporal resolution is more than adequate to detect even a single spike induced alteration in the intracellular calcium concentration. Sharp electrodes are simultaneously used to induce and record

  13. Review of fast reactor activities

    Balz, W [Commission of the European Communities, Brussels (Belgium)

    1978-07-01

    The Commission of the European Communities continued its activities on the following lines: activities aimed at preparing for commercialization of fast breeder reactors which are essentially performed in the frame of Fast Reactor Coordinating Committee (FRCC); the execution of its own research program in the Joint Research Center. The report covers activities of the FRCC, of the Safety Working Group (SWG), the Whole Core Accident Code (WAC) subgroup, Containment (CONT) subgroup, Codes and Standards Working Group (CSWG). Research and development activities are concerned with LMFBR safety, subassembly thermal hydraulics, fuel-coolant interactions, post-accident heat removal, dynamic load response, safety related material properties, utilization limits of fast breeder fuels, plutonium and actinide aspects of nuclear fuel cycle.

  14. Review of fast reactor activities

    Balz, W.

    1978-01-01

    The Commission of the European Communities continued its activities on the following lines: activities aimed at preparing for commercialization of fast breeder reactors which are essentially performed in the frame of Fast Reactor Coordinating Committee (FRCC); the execution of its own research program in the Joint Research Center. The report covers activities of the FRCC, of the Safety Working Group (SWG), the Whole Core Accident Code (WAC) subgroup, Containment (CONT) subgroup, Codes and Standards Working Group (CSWG). Research and development activities are concerned with LMFBR safety, subassembly thermal hydraulics, fuel-coolant interactions, post-accident heat removal, dynamic load response, safety related material properties, utilization limits of fast breeder fuels, plutonium and actinide aspects of nuclear fuel cycle

  15. Beam and spin dynamics in the fast ramping storage ring ELSA: Concepts and measures to increase beam energy, current and polarization

    Hillert, Wolfgang; Balling, Andreas; Boldt, Oliver; Dieckmann, Andreas; Eberhardt, Maren; Frommberger, Frank; Heiliger, Dominik; Heurich, Nikolas; Koop, Rebecca; Klarner, Fabian; Preisner, Oliver; Proft, Dennis; Pusch, Thorsten; Roth, André; Sauerland, Dennis; Schedler, Manuel; Schmidt, Jan Felix; Switka, Michael; Thiry, Jens-Peter; Wittschen, Jürgen; Zander, Sven

    2017-01-01

    The electron accelerator facility ELSA has been operated for almost 30 years serving nuclear physics experiments investigating the sub-nuclear structure of matter. Within the 12 years funding period of the collaborative research center SFB/TR 16, linearly and circularly polarized photon beams with energies up to more than 3 GeV were successfully delivered to photoproduction experiments. In order to fulfill the increasing demands on beam polarization and intensity, a comprehensive research and upgrade program has been carried out. Beam and spin dynamics have been studied theoretically and experimentally, and sophisticated new devices have been developed and installed. The improvements led to a significant increase of the available beam polarization and intensity. A further increase of beam energy seems feasible with the implementation of superconducting cavities.

  16. Effect of the nitrogen incorporation and fast carrier dynamics in (In,Ga)AsN/GaP self-assembled quantum dots

    Gauthier, J.-P.; Almosni, S.; Léger, Y.; Perrin, M.; Even, J.; Cornet, C., E-mail: charles.cornet@insa-rennes.fr; Durand, O. [UMR FOTON, CNRS, INSA-Rennes, F-35708 Rennes (France); Robert, C. [Tyndall National Institute, University College Cork, Lee Maltings, Cork (Ireland); Balocchi, A.; Carrère, H.; Marie, X. [Université de Toulouse, INSA-CNRS-UPS, LPCNO, F-31077 Toulouse (France)

    2014-12-15

    We report on the structural and optical properties of (In,Ga)AsN self-assembled quantum dots grown on GaP (001) substrate. A comparison with nitrogen free (In,Ga)As system is presented, showing a clear modification of growth mechanisms and a significant shift of the photoluminescence spectrum. Low temperature carrier recombination dynamics is studied by time-resolved photoluminescence, highlighting a drastic reduction of the characteristic decay-time when nitrogen is incorporated in the quantum dots. Room temperature photoluminescence is observed at 840 nm. These results reveal the potential of (In,Ga)AsN as an efficient active medium monolithically integrated on Si for laser applications.

  17. FINEDAN - an explicit finite-element calculation code for two-dimensional analyses of fast dynamic transients in nuclear reactor technology

    Adamik, V.; Matejovic, P.

    1989-01-01

    The problems are discussed of nonstationary, nonlinear dynamics of the continuum. A survey is presented of calculation methods in the given area with emphasis on the area of impact problems. A description is presented of the explicit finite elements method and its application to two-dimensional Cartesian and cylindrical configurations. Using the method the explicit calculation code FINEDAN was written which was tested in a series of verification calculations for different configurations and different types of continuum. The main characteristics are presented of the code and of some, of its practical applications. Envisaged trends of the development of the code and its possible applications in the technology of nuclear reactors are given. (author). 9 figs., 4 tabs., 10 refs

  18. Nanobodies: Chemical Functionalization Strategies and Intracellular Applications

    Schumacher, Dominik; Helma, Jonas; Schneider, Anselm F. L.; Leonhardt, Heinrich

    2018-01-01

    Abstract Nanobodies can be seen as next‐generation tools for the recognition and modulation of antigens that are inaccessible to conventional antibodies. Due to their compact structure and high stability, nanobodies see frequent usage in basic research, and their chemical functionalization opens the way towards promising diagnostic and therapeutic applications. In this Review, central aspects of nanobody functionalization are presented, together with selected applications. While early conjugation strategies relied on the random modification of natural amino acids, more recent studies have focused on the site‐specific attachment of functional moieties. Such techniques include chemoenzymatic approaches, expressed protein ligation, and amber suppression in combination with bioorthogonal modification strategies. Recent applications range from sophisticated imaging and mass spectrometry to the delivery of nanobodies into living cells for the visualization and manipulation of intracellular antigens. PMID:28913971

  19. Drosophila VAMP7 regulates Wingless intracellular trafficking.

    Gao, Han; He, Fang; Lin, Xinhua; Wu, Yihui

    2017-01-01

    Drosophila Wingless (Wg) is a morphogen that determines cell fate during development. Previous studies have shown that endocytic pathways regulate Wg trafficking and signaling. Here, we showed that loss of vamp7, a gene required for vesicle fusion, dramatically increased Wg levels and decreased Wg signaling. Interestingly, we found that levels of Dally-like (Dlp), a glypican that can interact with Wg to suppress Wg signaling at the dorsoventral boundary of the Drosophila wing, were also increased in vamp7 mutant cells. Moreover, Wg puncta in Rab4-dependent recycling endosomes were Dlp positive. We hypothesize that VAMP7 is required for Wg intracellular trafficking and the accumulation of Wg in Rab4-dependent recycling endosomes might affect Wg signaling.

  20. Intracellular pH in sperm physiology.

    Nishigaki, Takuya; José, Omar; González-Cota, Ana Laura; Romero, Francisco; Treviño, Claudia L; Darszon, Alberto

    2014-08-01

    Intracellular pH (pHi) regulation is essential for cell function. Notably, several unique sperm ion transporters and enzymes whose elimination causes infertility are either pHi dependent or somehow related to pHi regulation. Amongst them are: CatSper, a Ca(2+) channel; Slo3, a K(+) channel; the sperm-specific Na(+)/H(+) exchanger and the soluble adenylyl cyclase. It is thus clear that pHi regulation is of the utmost importance for sperm physiology. This review briefly summarizes the key components involved in pHi regulation, their characteristics and participation in fundamental sperm functions such as motility, maturation and the acrosome reaction. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Nanobodies: Chemical Functionalization Strategies and Intracellular Applications.

    Schumacher, Dominik; Helma, Jonas; Schneider, Anselm F L; Leonhardt, Heinrich; Hackenberger, Christian P R

    2018-02-23

    Nanobodies can be seen as next-generation tools for the recognition and modulation of antigens that are inaccessible to conventional antibodies. Due to their compact structure and high stability, nanobodies see frequent usage in basic research, and their chemical functionalization opens the way towards promising diagnostic and therapeutic applications. In this Review, central aspects of nanobody functionalization are presented, together with selected applications. While early conjugation strategies relied on the random modification of natural amino acids, more recent studies have focused on the site-specific attachment of functional moieties. Such techniques include chemoenzymatic approaches, expressed protein ligation, and amber suppression in combination with bioorthogonal modification strategies. Recent applications range from sophisticated imaging and mass spectrometry to the delivery of nanobodies into living cells for the visualization and manipulation of intracellular antigens. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  2. Intracellular Signalling by C-Peptide

    Claire E. Hills

    2008-01-01

    Full Text Available C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na+/K+ ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes.

  3. Intracellular sphingosine releases calcium from lysosomes.

    Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

    2015-11-27

    To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC.

  4. [Limbic encephalitis with antibodies against intracellular antigens].

    Morita, Akihiko; Kamei, Satoshi

    2010-04-01

    Limbic encephalitis is a paraneoplastic syndrome that is often associated with small cell lung cancer (SCLC), breast cancer, testicular tumors, teratoma, Hodgkin's lymphoma and thymoma. The common clinical manifestations of limbic encephalitis are subacute onset, cognitive dysfunction, seizures and psychiatric symptoms. Paraneoplastic neurological disorders are considered to occur because of cytotoxic T cell responses and antibodies against target neuronal proteins that are usually expressed by an underlying tumor. The main intracellular antigens related to limbic encephalitis are Hu, Ma2, and less frequently CV2/CRMP5 and amphiphysin. The anti-Hu antibody, which is involved in cerebellar degeneration and extensive or multifocal encephalomyelitis such as limbic encephalitis is closely associated with a history of smoking and SCLC. The anti-Ma2 antibody is associated with encephalitis of the limbic system, hypothalamus and brain-stem. For this reason, some patients with limbic encephalitis have sleep disorders (including REM sleep abnormalities), severe hypokinesis and gaze palsy in addition to limbic dysfunction. In men aged less than 50 years, anti-Ma2 antibody encephalitis is almost always associated with testicular germ-cell tumors that are occasionally difficult to detect. In older men and women, the most common tumors are non-SCLC and breast cancer. Limbic encephalitis associated with cell-surface antigens (e.g., voltage-gated potassium channels, NMDA receptors) is mediated by antibodies and often improves after a reduction in the antibody titer and after tumor resection. Patients with antibodies against intracellular antigens, except for those with anti-Ma2 antibodies and testicular tumors, are less responsive. Early diagnosis and treatment with immunotherapy, tumor resection or both are important for improving or stabilizing the condition of limbic encephalitis.

  5. Qualitative assessment of ultra-fast non-Grotthuss proton dynamics in S1 excited state of liquid H2O from ab initio time-dependent density functional theory★

    Ziaei, Vafa; Bredow, Thomas

    2017-11-01

    We study qualitatively ultra-fast proton transfer (PT) in the first singlet (S1) state of liquid water (absorption onset) through excited-state dynamics by means of time-dependent density functional theory and ab initio Born-Oppenheimer molecular dynamics. We find that after the initial excitation, a PT occurs in S1 in form of a rapid jump to a neighboring water molecule, on which the proton either may rest for a relatively long period of time (as a consequence of possible defect in the hydrogen bond network) followed by back and forth hops to its neighboring water molecule or from which it further moves to the next water molecule accompanied by back and forth movements. In this way, the proton may become delocalized over a long water wire branch, followed again by back and forth jumps or short localization on a water molecule for some femtoseconds. As a result, the mechanism of PT in S1 is in most cases highly non-Grotthuss-like, delayed and discrete. Furthermore, upon PT an excess charge is ejected to the solvent trap, the so-called solvated electron. The spatial extent of the ejected solvated electron is mainly localized within one solvent shell with overlappings on the nearest neighbor water molecules and delocalizing (diffuse) tails extending beyond the first solvent sphere. During the entire ultra-short excited-state dynamics the remaining OH radical from the initially excited water molecule exhibits an extremely low mobility and is non-reactive. Supplementary material in the form of one pdf file available from the Journal web page at http://https://doi.org/10.1140/epjb/e2017-80329-7.

  6. Development of a plant dynamics computer code for analysis of a supercritical carbon dioxide Brayton cycle energy converter coupled to a natural circulation lead-cooled fast reactor.

    Moisseytsev, A.; Sienicki, J. J.

    2007-03-08

    STAR-LM is a lead-cooled pool-type fast reactor concept operating under natural circulation of the coolant. The reactor core power is 400 MWt. The open-lattice core consists of fuel pins attached to the core support plate, (the does not consist of removable fuel assemblies). The coolant flows outside of the fuel pins. The fuel is transuranic nitride, fabricated from reprocessed LWR spent fuel. The cladding material is HT-9 stainless steel; the steady-state peak cladding temperature is 650 C. The coolant is single-phase liquid lead under atmospheric pressure; the core inlet and outlet temperatures are 438 C and 578 C, respectively. (The Pb coolant freezing and boiling temperatures are 327 C and 1749 C, respectively). The coolant is contained inside of a reactor vessel. The vessel material is Type 316 stainless steel. The reactor is autonomous meaning that the reactor power is self-regulated based on inherent reactivity feedbacks and no external power control (through control rods) is utilized. The shutdown (scram) control rods are used for startup and shutdown and to stop the fission reaction in case of an emergency. The heat from the reactor is transferred to the S-CO{sub 2} Brayton cycle in in-reactor heat exchangers (IRHX) located inside the reactor vessel. The IRHXs are shell-and-tube type heat exchangers with lead flowing downwards on the shell side and CO{sub 2} flowing upwards on the tube side. No intermediate circuit is utilized. The guard vessel surrounds the reactor vessel to contain the coolant, in the very unlikely event of reactor vessel failure. The Reactor Vessel Auxiliary Cooling System (RVACS) implementing the natural circulation of air flowing upwards over the guard vessel is used to cool the reactor, in the case of loss of normal heat removal through the IRHXs. The RVACS is always in operation. The gap between the vessels is filled with liquid lead-bismuth eutectic (LBE) to enhance the heat removal by air by significantly reducing the thermal

  7. Single-cell intracellular nano-pH probes†

    Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

    2015-01-01

    Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular p...

  8. The truncated conjugate gradient (TCG), a non-iterative/fixed-cost strategy for computing polarization in molecular dynamics: Fast evaluation of analytical forces

    Aviat, Félix; Lagardère, Louis; Piquemal, Jean-Philip

    2017-10-01

    In a recent paper [F. Aviat et al., J. Chem. Theory Comput. 13, 180-190 (2017)], we proposed the Truncated Conjugate Gradient (TCG) approach to compute the polarization energy and forces in polarizable molecular simulations. The method consists in truncating the conjugate gradient algorithm at a fixed predetermined order leading to a fixed computational cost and can thus be considered "non-iterative." This gives the possibility to derive analytical forces avoiding the usual energy conservation (i.e., drifts) issues occurring with iterative approaches. A key point concerns the evaluation of the analytical gradients, which is more complex than that with a usual solver. In this paper, after reviewing the present state of the art of polarization solvers, we detail a viable strategy for the efficient implementation of the TCG calculation. The complete cost of the approach is then measured as it is tested using a multi-time step scheme and compared to timings using usual iterative approaches. We show that the TCG methods are more efficient than traditional techniques, making it a method of choice for future long molecular dynamics simulations using polarizable force fields where energy conservation matters. We detail the various steps required for the implementation of the complete method by software developers.

  9. Dynamic motion analysis of fetuses with central nervous system disorders by cine magnetic resonance imaging using fast imaging employing steady-state acquisition and parallel imaging: a preliminary result.

    Guo, Wan-Yuo; Ono, Shigeki; Oi, Shizuo; Shen, Shu-Huei; Wong, Tai-Tong; Chung, Hsiao-Wen; Hung, Jeng-Hsiu

    2006-08-01

    The authors present a novel cine magnetic resonance (MR) imaging, two-dimensional (2D) fast imaging employing steady-state acquisition (FIESTA) technique with parallel imaging. It achieves temporal resolution at less than half a second as well as high spatial resolution cine imaging free of motion artifacts for evaluating the dynamic motion of fetuses in utero. The information obtained is used to predict postnatal outcome. Twenty-five fetuses with anomalies were studied. Ultrasonography demonstrated severe abnormalities in five of the fetuses; the other 20 fetuses constituted a control group. The cine fetal MR imaging demonstrated fetal head, neck, trunk, extremity, and finger as well as swallowing motions. Imaging findings were evaluated and compared in fetuses with major central nervous system (CNS) anomalies in five cases and minor CNS, non-CNS, or no anomalies in 20 cases. Normal motility was observed in the latter group. For fetuses in the former group, those with abnormal motility failed to survive after delivery, whereas those with normal motility survived with functioning preserved. The power deposition of radiofrequency, presented as specific absorption rate (SAR), was calculated. The SAR of FIESTA was approximately 13 times lower than that of conventional MR imaging of fetuses obtained using single-shot fast spin echo sequences. The following conclusions are drawn: 1) Fetal motion is no longer a limitation for prenatal imaging after the implementation of parallel imaging with 2D FIESTA, 2) Cine MR imaging illustrates fetal motion in utero with high clinical reliability, 3) For cases involving major CNS anomalies, cine MR imaging provides information on extremity motility in fetuses and serves as a prognostic indicator of postnatal outcome, and 4) The cine MR used to observe fetal activity is technically 2D and conceptually three-dimensional. It provides four-dimensional information for making proper and timely obstetrical and/or postnatal management

  10. Fasting and rheumatic diseases

    Mohammad Hassan Jokar

    2015-01-01

    Fasting is one of the important religious practices of Muslims, in which the individuals abstain from eating and drinking from dawn to sunset. Fasting is not obligatory or even not allowed, in case it causes health problems to the fasting individual. Rheumatic diseases are a major group of chronic diseases which can bring about numerous problems while fasting. The aim of this article is to review the impact of Islamic fasting on rheumatic patients, based on the scientific evidences.

  11. Enhanced NMDA receptor-mediated intracellular calcium signaling in magnocellular neurosecretory neurons in heart failure rats.

    Stern, Javier E; Potapenko, Evgeniy S

    2013-08-15

    An enhanced glutamate excitatory function within the hypothalamic supraoptic and paraventricluar nuclei is known to contribute to increased neurosecretory and presympathetic neuronal activity, and hence, neurohumoral activation, during heart failure (HF). Still, the precise mechanisms underlying enhanced glutamate-driven neuronal activity in HF remain to be elucidated. Here, we performed simultaneous electrophysiology and fast confocal Ca²⁺ imaging to determine whether altered N-methyl-d-aspartate (NMDA) receptor-mediated changes in intracellular Ca²⁺ levels (NMDA-ΔCa²⁺) occurred in hypothalamic magnocellular neurosecretory cells (MNCs) in HF rats. We found that activation of NMDA receptors resulted in a larger ΔCa²⁺ in MNCs from HF when compared with sham rats. The enhanced NMDA-ΔCa²⁺ was neither dependent on the magnitude of the NMDA-mediated current (voltage clamp) nor on the degree of membrane depolarization or firing activity evoked by NMDA (current clamp). Differently from NMDA receptor activation, firing activity evoked by direct membrane depolarization resulted in similar changes in intracellular Ca²⁺ in sham and HF rats. Taken together, our results support a relatively selective alteration of intracellular Ca²⁺ homeostasis and signaling following activation of NMDA receptors in MNCs during HF. The downstream functional consequences of such altered ΔCa²⁺ signaling during HF are discussed.

  12. Intracellular pH-sensing using core/shell silica nanoparticles.

    Korzeniowska, B; Woolley, R; DeCourcey, J; Wencel, D; Loscher, C E; McDonagh, C

    2014-07-01

    An in-depth understanding of biochemical processes occurring within biological systems is key for early diagnosis of disease and identification of appropriate treatments. Nanobiophotonics offers huge potential benefits for intracellular diagnostics and therapeutics. Intracellular sensing using fluorescent nanoparticles is a potentially useful tool for real-time, in vivo monitoring of important cellular analytes. This work is focused on synthesis of optical chemical nanosensors for the quantitative analysis of pH inside living cells. The structure of the nanosensor comprises a biofriendly silica matrix with co-encapsulated Texas Red, acting as a reference dye, and pH-sensitive fluorescein isothiocyanate enabling ratiometric quantitative environmental detection. In order to obtain silica-based nanoparticles -70 nm in size, a modified sol-gel-based Stöber method was employed. The potential of these nanosensors for intracellular pH monitoring is demonstrated inside a live human embryonic kidney cell line whereby a significant change in fluorescence is observed when the cell pH is switched from acidic to basic. High loading efficiencies of nanoparticles into the cells is seen, with little effect on cell morphology even following extended nanoparticle exposure (up to 72 h). Nanoparticle incubation time and the fast response of the nanosensor (-2 s) make it a very powerful tool in monitoring the processes occurring within the cytosol.

  13. Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes

    Radogna, Flavia; Paternoster, Laura; De Nicola, Milena; Cerella, Claudia; Ammendola, Sergio; Bedini, Annalida; Tarzia, Giorgio; Aquilano, Katia; Ciriolo, Maria; Ghibelli, Lina

    2009-01-01

    Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxidant activity, showing that melatonin is able to stimulate production of intracellular reactive oxygen species (ROS). Here we show that on U937 human monocytes melatonin promotes intracellular ROS in a fast (< 1 min) and transient (up to 5-6 h) way. Melatonin equally elicits its pro-radical effect on a set of normal or tumor leukocytes; intriguingly, ROS production does not lead to oxidative stress, as shown by absence of protein carbonylation, maintenance of free thiols, preservation of viability and regular proliferation rate. ROS production is independent from MT1/MT2 receptor interaction, since a) requires micromolar (as opposed to nanomolar) doses of melatonin; b) is not contrasted by the specific MT1/MT2 antagonist luzindole; c) is not mimicked by a set of MT1/MT2 high affinity melatonin analogues. Instead, chlorpromazine, the calmodulin inhibitor shown to prevent melatonin-calmodulin interaction, also prevents melatonin pro-radical effect, suggesting that the low affinity binding to calmodulin (in the micromolar range) may promote ROS production.

  14. Temporal protein expression pattern in intracellular signalling ...

    Supplementary figure 1. Protein expression dynamics observed in Experiment, Synchronous and. Asynchronous simulation. .... molecular basis for T cell suppression by IL-10: CD28-asso- ciated IL-10 receptor inhibits CD28 tyrosine ...

  15. Photonic crystal fiber monitors for intracellular ice formation

    Battinelli, Emily; Reimlinger, Mark; Wynne, Rosalind

    2012-04-01

    An all-silica steering wheel photonic crystal fiber (SW-PCF) device with real-time analysis for cellular temperature sensing is presented. Results are provided for water-filled SW-PCF fibers experiencing cooling down near -40°C. Cellular temperature sensors with fast response times are of interest particularly to the study of cryopreservation, which has been influential in applications such as tissue preservation, food quality control, genetic engineering, as well as drug discovery and in- vitro toxin testing. Results of this investigation are relevant to detection of intracellular ice formation (IIF) and better understanding cell freezing at very low temperatures. IIF detection is determined as a function of absorption occurring within the core of the SW-PCF. The SW-PCF has a 3.3μm core diameter, 125μm outer diameter and steering wheel-like air hole pattern with triangular symmetry, with a 20μm radius. One end of a 0.6m length of the SW-PCF is placed between two thermoelectric coolers, filled with ~0.1μL water. This end is butt coupled to a 0.5m length of single mode fiber (SMF), the distal end of the fiber is then inserted into an optical spectrum analyzer. A near-IR light source is guided through the fiber, such that the absorption of the material in the core can be measured. Spectral characteristics demonstrated by the optical absorption of the water sample were present near the 1300-1700nm window region with strongest peaks at 1350, 1410 and 1460nm, further shifting of the absorption peaks is possible at cryogenic temperatures making this device suitable for IIF monitoring applications.

  16. Intracellular magnetophoresis of amyloplasts and induction of root curvature

    Kuznetsov, O. A.; Hasenstein, K. H.

    1996-01-01

    High-gradient magnetic fields (HGMFs) were used to induce intracellular magnetophoresis of amyloplasts. The HGMFs were generated by placing a small ferromagnetic wedge into a uniform magnetic field or at the gap edge between two permanent magnets. In the vicinity of the tip of the wedge the dynamic factor of the magnetic field, delta(H2/2), was about 10(9) Oe2.cm-1, which subjected the amyloplasts to a force comparable to that of gravity. When roots of 2-d-old seedlings of flax (Linum usitatissimum L.) were positioned vertically and exposed to an HGMF, curvature away from the wedge was transient and lasted approximately 1 h. Average curvature obtained after placing magnets, wedge and seedlings on a 1-rpm clinostat for 2 h was 33 +/- 5 degrees. Roots of horizontally placed control seedlings without rotation curved about 47 +/- 4 degrees. The time course of curvature and changes in growth rate were similar for gravicurvature and for root curvature induced by HGMFs. Microscopy showed displacement of amyloplasts in vitro and in vivo. Studies with Arabidopsis thaliana (L.) Heynh. showed that the wild type responded to HGMFs but the starchless mutant TC7 did not. The data indicate that a magnetic force can be used to study the gravisensing and response system of roots.

  17. The mechanical environment modulates intracellular calcium oscillation activities of myofibroblasts.

    Charles Godbout

    Full Text Available Myofibroblast contraction is fundamental in the excessive tissue remodeling that is characteristic of fibrotic tissue contractures. Tissue remodeling during development of fibrosis leads to gradually increasing stiffness of the extracellular matrix. We propose that this increased stiffness positively feeds back on the contractile activities of myofibroblasts. We have previously shown that cycles of contraction directly correlate with periodic intracellular calcium oscillations in cultured myofibroblasts. We analyze cytosolic calcium dynamics using fluorescent calcium indicators to evaluate the possible impact of mechanical stress on myofibroblast contractile activity. To modulate extracellular mechanics, we seeded primary rat subcutaneous myofibroblasts on silicone substrates and into collagen gels of different elastic modulus. We modulated cell stress by cell growth on differently adhesive culture substrates, by restricting cell spreading area on micro-printed adhesive islands, and depolymerizing actin with Cytochalasin D. In general, calcium oscillation frequencies in myofibroblasts increased with increasing mechanical challenge. These results provide new insight on how changing mechanical conditions for myofibroblasts are encoded in calcium oscillations and possibly explain how reparative cells adapt their contractile behavior to the stresses occurring in normal and pathological tissue repair.

  18. Microrheometric upconversion-based techniques for intracellular viscosity measurements

    Rodríguez-Sevilla, Paloma; Zhang, Yuhai; de Sousa, Nuno; Marqués, Manuel I.; Sanz-Rodríguez, Francisco; Jaque, Daniel; Liu, Xiaogang; Haro-González, Patricia

    2017-08-01

    Rheological parameters (viscosity, creep compliance and elasticity) play an important role in cell function and viability. For this reason different strategies have been developed for their study. In this work, two new microrheometric techniques are presented. Both methods take advantage of the analysis of the polarized emission of an upconverting particle to determine its orientation inside the optical trap. Upconverting particles are optical materials that are able to convert infrared radiation into visible light. Their usefulness has been further boosted by the recent demonstration of their three-dimensional control and tracking by single beam infrared optical traps. In this work it is demonstrated that optical torques are responsible of the stable orientation of the upconverting particle inside the trap. Moreover, numerical calculations and experimental data allowed to use the rotation dynamics of the optically trapped upconverting particle for environmental sensing. In particular, the cytoplasm viscosity could be measured by using the rotation time and thermal fluctuations of an intracellular optically trapped upconverting particle, by means of the two previously mentioned microrheometric techniques.

  19. Cell type-specific response to high intracellular loading of polyacrylic acid-coated magnetic nanoparticles

    Lojk, Jasna; Bregar, Vladimir B; Rajh, Maruša; Miš, Katarina; Kreft, Mateja Erdani; Pirkmajer, Sergej; Veranič, Peter; Pavlin, Mojca

    2015-01-01

    Magnetic nanoparticles (NPs) are a special type of NP with a ferromagnetic, electron-dense core that enables several applications such as cell tracking, hyperthermia, and magnetic separation, as well as multimodality. So far, superparamagnetic iron oxide NPs (SPIONs) are the only clinically approved type of metal oxide NPs, but cobalt ferrite NPs have properties suitable for biomedical applications as well. In this study, we analyzed the cellular responses to magnetic cobalt ferrite NPs coated with polyacrylic acid (PAA) in three cell types: Chinese Hamster Ovary (CHO), mouse melanoma (B16) cell line, and primary human myoblasts (MYO). We compared the internalization pathway, intracellular trafficking, and intracellular fate of our NPs using fluorescence and transmission electron microscopy (TEM) as well as quantified NP uptake and analyzed uptake dynamics. We determined cell viability after 24 or 96 hours’ exposure to increasing concentrations of NPs, and quantified the generation of reactive oxygen species (ROS) upon 24 and 48 hours’ exposure. Our NPs have been shown to readily enter and accumulate in cells in high quantities using the same two endocytic pathways; mostly by macropinocytosis and partially by clathrin-mediated endocytosis. The cell types differed in their uptake rate, the dynamics of intracellular trafficking, and the uptake capacity, as well as in their response to higher concentrations of internalized NPs. The observed differences in cell responses stress the importance of evaluation of NP–cell interactions on several different cell types for better prediction of possible toxic effects on different cell and tissue types in vivo. PMID:25733835

  20. Regulation of intracellular pH in cnidarians: response to acidosis in Anemonia viridis.

    Laurent, Julien; Venn, Alexander; Tambutté, Éric; Ganot, Philippe; Allemand, Denis; Tambutté, Sylvie

    2014-02-01

    The regulation of intracellular pH (pHi) is a fundamental aspect of cell physiology that has received little attention in studies of the phylum Cnidaria, which includes ecologically important sea anemones and reef-building corals. Like all organisms, cnidarians must maintain pH homeostasis to counterbalance reductions in pHi, which can arise because of changes in either intrinsic or extrinsic parameters. Corals and sea anemones face natural daily changes in internal fluids, where the extracellular pH can range from 8.9 during the day to 7.4 at night. Furthermore, cnidarians are likely to experience future CO₂-driven declines in seawater pH, a process known as ocean acidification. Here, we carried out the first mechanistic investigation to determine how cnidarian pHi regulation responds to decreases in extracellular and intracellular pH. Using the anemone Anemonia viridis, we employed confocal live cell imaging and a pH-sensitive dye to track the dynamics of pHi after intracellular acidosis induced by acute exposure to decreases in seawater pH and NH₄Cl prepulses. The investigation was conducted on cells that contained intracellular symbiotic algae (Symbiodinium sp.) and on symbiont-free endoderm cells. Experiments using inhibitors and Na⁺-free seawater indicate a potential role of Na⁺/H⁺ plasma membrane exchangers (NHEs) in mediating pHi recovery following intracellular acidosis in both cell types. We also measured the buffering capacity of cells, and obtained values between 20.8 and 43.8 mM per pH unit, which are comparable to those in other invertebrates. Our findings provide the first steps towards a better understanding of acid-base regulation in these basal metazoans, for which information on cell physiology is extremely limited. © 2013 FEBS.

  1. LIPID SYNTHESIS, INTRACELLULAR TRANSPORT, AND SECRETION

    Stein, Olga; Stein, Yechezkiel

    1967-01-01

    In the mammary glands of lactating albino mice injected intravenously with 9, 10-oleic acid-3H or 9, 10-palmitic acid-3H, it has been shown that the labeled fatty acids are incorporated into mammary gland glycerides. The labeled lipid in the mammary gland 1 min after injection was in esterified form (> 95%), and the radioautographic reaction was seen over the rough endoplasmic reticulum and over lipid droplets, both intracellular and intraluminal. At 10–60 min after injection, the silver grains were concentrated predominantly over lipid droplets. There was no concentration of radioactivity over the granules in the Golgi apparatus, at any time interval studied. These findings were interpreted to indicate that after esterification of the fatty acid into glycerides in the rough endoplasmic reticulum an in situ aggregation of lipid occurs, with acquisition of droplet form. The release of the lipid into the lumen proceeds directly and not through the Golgi apparatus, in contradistinction to the mode of secretion of casein in the mammary gland or of lipoprotein in the liver. The presence of strands of endoplasmic reticulum attached to intraluminal lipid droplets provides a structural counterpart to the milk microsomes described in ruminant milk. PMID:6033535

  2. Endothelial remodelling and intracellular calcium machinery.

    Moccia, F; Tanzi, F; Munaron, L

    2014-05-01

    Rather being an inert barrier between vessel lumen and surrounding tissues, vascular endothelium plays a key role in the maintenance of cardiovascular homeostasis. The de-endothelialization of blood vessels is regarded as the early event that results in the onset of severe vascular disorders, including atherosclerosis, acute myocardial infarction, brain stroke, and aortic aneurysm. Restoration of the endothelial lining may be accomplished by the activation of neighbouring endothelial cells (ECs) freed by contact inhibition and by circulating endothelial progenitor cells (EPCs). Intracellular Ca(2+) signalling is essential to promote wound healing: however, the molecular underpinnings of the Ca(2+) response to injury are yet to be fully elucidated. Similarly, the components of the Ca(2+) toolkit that drive EPC incorporation into denuded vessels are far from being fully elucidated. The present review will survey the current knowledge on the role of Ca(2+) signalling in endothelial repair and in EPC activation. We propose that endothelial regeneration might be boosted by intraluminal release of specific Ca(2+) channel agonists or by gene transfer strategies aiming to enhance the expression of the most suitable Ca(2+) channels at the wound site. In this view, connexin (Cx) channels/hemichannels and store-operated Ca(2+) entry (SOCE) stand amid the most proper routes to therapeutically induce the regrowth of denuded vessels. Cx stimulation might trigger the proliferative and migratory behaviour of ECs facing the lesion site, whereas activation of SOCE is likely to favour EPC homing to the wounded vessel.

  3. Intracellular events regulating cross-presentation

    Peter eCresswell

    2012-06-01

    Full Text Available Cross-presentation plays a fundamental role in the induction of CD8-T cell immunity. However, although more than three decades have passed since its discovery, surprisingly little is known about the exact mechanisms involved. Here we give an overview of the components involved at different stages of this process. First, antigens must be internalized into the cross-presenting cell. The involvement of different receptors, method of antigen uptake, and nature of the antigen can influence intracellular trafficking and access to the cross-presentation pathway. Once antigens access the endocytic system, different requirements for endosomal/phagosomal processing arise, such as proteolysis and reduction of disulfide bonds. The majority of cross-presented peptides are generated by proteasomal degradation. Therefore, antigens must cross a membrane barrier in a manner analogous to the fate of misfolded proteins in the endoplasmic reticulum (ER that are retrotranslocated into the cytosol for degradation. Indeed, some components of the ER-associated degradation (ERAD machinery have been implicated in cross-presentation. Further complicating the matter, endosomal and phagosomal compartments have been suggested as alternative sites to the ER for loading of peptides on MHC class I molecules. Finally, the antigen presenting cells involved, particularly dendritic cell subsets and their state of maturation, influence the efficiency of cross-presentation.

  4. Intracellular recording from a spider vibration receptor.

    Gingl, Ewald; Burger, Anna-M; Barth, Friedrich G

    2006-05-01

    The present study introduces a new preparation of a spider vibration receptor that allows intracellular recording of responses to natural mechanical or electrical stimulation of the associated mechanoreceptor cells. The spider vibration receptor is a lyriform slit sense organ made up of 21 cuticular slits located on the distal end of the metatarsus of each walking leg. The organ is stimulated when the tarsus receives substrate vibrations, which it transmits to the organ's cuticular structures, reducing the displacement to about one tenth due to geometrical reasons. Current clamp recording was used to record action potentials generated by electrical or mechanical stimuli. Square pulse stimulation identified two groups of sensory cells, the first being single-spike cells which generated only one or two action potentials and the second being multi-spike cells which produced bursts of action potentials. When the more natural mechanical sinusoidal stimulation was applied, differences in adaptation rate between the two cell types remained. In agreement with prior extracellular recordings, both cell types showed a decrease in the threshold tarsus deflection with increasing stimulus frequency. Off-responses to mechanical stimuli have also been seen in the metatarsal organ for the first time.

  5. Intracellular Drug Bioavailability: Effect of Neutral Lipids and Phospholipids.

    Treyer, Andrea; Mateus, André; Wiśniewski, Jacek R; Boriss, Hinnerk; Matsson, Pär; Artursson, Per

    2018-06-04

    Intracellular unbound drug concentrations are the pharmacologically relevant concentrations for targets inside cells. Intracellular drug concentrations are determined by multiple processes, including the extent of drug binding to intracellular structures. The aim of this study was to evaluate the effect of neutral lipid (NL) and phospholipid (PL) levels on intracellular drug disposition. The NL and/or PL content of 3T3-L1 cells were enhanced, resulting in phenotypes (in terms of morphology and proteome) reminiscent of adipocytes (high NL and PL) or mild phospholipidosis (only high PL). Intracellular bioavailability ( F ic ) was then determined for 23 drugs in these cellular models and in untreated wild-type cells. A higher PL content led to higher intracellular drug binding and a lower F ic . The induction of NL did not further increase drug binding but led to altered F ic due to increased lysosomal pH. Further, there was a good correlation between binding to beads coated with pure PL and intracellular drug binding. In conclusion, our results suggest that PL content is a major determinant of drug binding in cells and that PL beads may constitute a simple alternative to estimating this parameter. Further, the presence of massive amounts of intracellular NLs did not influence drug binding significantly.

  6. Real-Time DNP NMR Observations of Acetic Acid Uptake, Intracellular Acidification, and of Consequences for Glycolysis and Alcoholic Fermentation in Yeast

    Jensen, Pernille Rose; Karlsson, Magnus; Lerche, Mathilde Hauge

    2013-01-01

    Uptake and upshot in vivo: Straightforward methods that permit the real-time observation of organic acid influx, intracellular acidification, and concomitant effects on cellular-reaction networks are crucial for improved bioprocess monitoring and control (see scheme). Herein, dynamic nuclear pola...... polarization (DNP) NMR is used to observe acetate influx, ensuing intracellular acidification and the metabolic consequences on alcoholic fermentation and glycolysis in living cells....

  7. Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols.

    Pinu, Farhana R; Villas-Boas, Silas G; Aggio, Raphael

    2017-10-23

    Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

  8. Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols

    Farhana R. Pinu

    2017-10-01

    Full Text Available Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

  9. Shuttling of G protein subunits between the plasma membrane and intracellular membranes.

    Chisari, Mariangela; Saini, Deepak Kumar; Kalyanaraman, Vani; Gautam, Narasimhan

    2007-08-17

    Heterotrimeric G proteins (alphabetagamma) mediate the majority of signaling pathways in mammalian cells. It is long held that G protein function is localized to the plasma membrane. Here we examined the spatiotemporal dynamics of G protein localization using fluorescence recovery after photobleaching, fluorescence loss in photobleaching, and a photoswitchable fluorescent protein, Dronpa. Unexpectedly, G protein subunits shuttle rapidly (t1/2 plasma membrane and intracellular membranes. We show that consistent with such shuttling, G proteins constitutively reside in endomembranes. Furthermore, we show that shuttling is inhibited by 2-bromopalmitate. Thus, contrary to present thought, G proteins do not reside permanently on the plasma membrane but are constantly testing the cytoplasmic surfaces of the plasma membrane and endomembranes to maintain G protein pools in intracellular membranes to establish direct communication between receptors and endomembranes.

  10. Size-Dependent Regulation of Intracellular Trafficking of Polystyrene Nanoparticle-Based Drug-Delivery Systems.

    Wang, Ting; Wang, Lu; Li, Xiaoming; Hu, Xingjie; Han, Yuping; Luo, Yao; Wang, Zejun; Li, Qian; Aldalbahi, Ali; Wang, Lihua; Song, Shiping; Fan, Chunhai; Zhao, Yun; Wang, Maolin; Chen, Nan

    2017-06-07

    Nanoparticles (NPs) have shown great promise as intracellular imaging probes or nanocarriers and are increasingly being used in biomedical applications. A detailed understanding of how NPs get "in and out" of cells is important for developing new nanomaterials with improved selectivity and less cytotoxicity. Both physical and chemical characteristics have been proven to regulate the cellular uptake of NPs. However, the exocytosis process and its regulation are less explored. Herein, we investigated the size-regulated endocytosis and exocytosis of carboxylated polystyrene (PS) NPs. PS NPs with a smaller size were endocytosed mainly through the clathrin-dependent pathway, whereas PS NPs with a larger size preferred caveolae-mediated endocytosis. Furthermore, our results revealed exocytosis of larger PS NPs and tracked the dynamic process at the single-particle level. These results indicate that particle size is a key factor for the regulation of intracellular trafficking of NPs and provide new insight into the development of more effective cellular nanocarriers.

  11. Fast-track hip and knee arthroplasty

    Husted, Henrik

    2012-01-01

    Fast-track hip and knee arthroplasty aims at giving the patients the best available treatment at all times, being a dynamic entity. Fast-track combines evidence-based, clinical features with organizational optimization including a revision of traditions resulting in a streamlined pathway from...... on clinical and organizational aspects of fast-track hip and knee arthroplasty (I–IX). A detailed description of the fast-track set-up and its components is provided. Major results include identification of patient characteristics to predict length of stay and satisfaction with different aspects...... of the hospital stay (I); how to optimize analgesia by using a compression bandage in total knee arthroplasty (II); the clinical and organizational set-up facilitating or acting as barriers for early discharge (III); safety aspects following fast-track in the form of few readmissions in general (IV) and few...

  12. Imaging and controlling intracellular reactions: Lysosome transport as a function of diameter and the intracellular synthesis of conducting polymers

    Payne, Christine

    2014-03-01

    Eukaryotic cells are the ultimate complex environment with intracellular chemical reactions regulated by the local cellular environment. For example, reactants are sequestered into specific organelles to control local concentration and pH, motor proteins transport reactants within the cell, and intracellular vesicles undergo fusion to bring reactants together. Current research in the Payne Lab in the School of Chemistry and Biochemistry at Georgia Tech is aimed at understanding and utilizing this complex environment to control intracellular chemical reactions. This will be illustrated using two examples, intracellular transport as a function of organelle diameter and the intracellular synthesis of conducting polymers. Using single particle tracking fluorescence microscopy, we measured the intracellular transport of lysosomes, membrane-bound organelles, as a function of diameter as they underwent transport in living cells. Both ATP-dependent active transport and diffusion were examined. As expected, diffusion scales with the diameter of the lysosome. However, active transport is unaffected suggesting that motor proteins are insensitive to cytosolic drag. In a second example, we utilize intracellular complexity, specifically the distinct micro-environments of different organelles, to carry out chemical reactions. We show that catalase, found in the peroxisomes of cells, can be used to catalyze the polymerization of the conducting polymer PEDOT:PSS. More importantly, we have found that a range of iron-containing biomolecules are suitable catalysts with different iron-containing biomolecules leading to different polymer properties. These experiments illustrate the advantage of intracellular complexity for the synthesis of novel materials.

  13. Intracellular Localization of Arabidopsis Sulfurtransferases1

    Bauer, Michael; Dietrich, Christof; Nowak, Katharina; Sierralta, Walter D.; Papenbrock, Jutta

    2004-01-01

    Sulfurtransferases (Str) comprise a group of enzymes widely distributed in archaea, eubacteria, and eukaryota which catalyze the transfer of a sulfur atom from suitable sulfur donors to nucleophilic sulfur acceptors. In all organisms analyzed to date, small gene families encoding Str proteins have been identified. The gene products were localized to different compartments of the cells. Our interest concerns the localization of Str proteins encoded in the nuclear genome of Arabidopsis. Computer-based prediction methods revealed localization in different compartments of the cell for six putative AtStrs. Several methods were used to determine the localization of the AtStr proteins experimentally. For AtStr1, a mitochondrial localization was demonstrated by immunodetection in the proteome of isolated mitochondria resolved by one- and two-dimensional gel electrophoresis and subsequent blotting. The respective mature AtStr1 protein was identified by mass spectrometry sequencing. The same result was obtained by transient expression of fusion constructs with the green fluorescent protein in Arabidopsis protoplasts, whereas AtStr2 was exclusively localized to the cytoplasm by this method. Three members of the single-domain AtStr were localized in the chloroplasts as demonstrated by transient expression of green fluorescent protein fusions in protoplasts and stomata, whereas the single-domain AtStr18 was shown to be cytoplasmic. The remarkable subcellular distribution of AtStr15 was additionally analyzed by transmission electron immunomicroscopy using a monospecific antibody against green fluorescent protein, indicating an attachment to the thylakoid membrane. The knowledge of the intracellular localization of the members of this multiprotein family will help elucidate their specific functions in the organism. PMID:15181206

  14. Intracellular signaling by diffusion: can waves of hydrogen peroxide transmit intracellular information in plant cells?

    Vestergaard, Christian L.; Flyvbjerg, Henrik; Møller, Ian Max

    2012-01-01

    of the physical and biochemical conditions in plant cells. As model system, we use a H(2)O(2) signal originating at the plasma membrane (PM) and spreading through the cytosol. We consider two maximally simple types of signals, isolated pulses and harmonic oscillations. First we consider the basic limits......Amplitude- and frequency-modulated waves of Ca(2+) ions transmit information inside cells. Reactive Oxygen Species (ROS), specifically hydrogen peroxide, have been proposed to have a similar role in plant cells. We consider the feasibility of such an intracellular communication system in view...

  15. HCUP Fast Stats

    U.S. Department of Health & Human Services — HCUP Fast Stats provides easy access to the latest HCUP-based statistics for health information topics. HCUP Fast Stats uses visual statistical displays in...

  16. Fast food (image)

    Fast foods are quick, reasonably priced, and readily available alternatives to home cooking. While convenient and economical for a busy lifestyle, fast foods are typically high in calories, fat, saturated fat, ...

  17. Fast food tips (image)

    ... challenge to eat healthy when going to a fast food place. In general, avoiding items that are deep ... challenge to eat healthy when going to a fast food place. In general, avoiding items that are deep ...

  18. Fast plunges into Kerr black holes

    Hadar, Shahar [Racah Institute of Physics, Hebrew University,Jerusalem 91904 (Israel); Porfyriadis, Achilleas P.; Strominger, Andrew [Center for the Fundamental Laws of Nature, Harvard University,Cambridge, MA 02138 (United States)

    2015-07-15

    Most extreme-mass-ratio-inspirals of small compact objects into supermassive black holes end with a fast plunge from an eccentric last stable orbit. For rapidly rotating black holes such fast plunges may be studied in the context of the Kerr/CFT correspondence because they occur in the near-horizon region where dynamics are governed by the infinite dimensional conformal symmetry. In this paper we use conformal transformations to analytically solve for the radiation emitted from fast plunges into near-extreme Kerr black holes. We find perfect agreement between the gravity and CFT computations.

  19. Physiology of Ramadan fasting

    Shokoufeh Bonakdaran

    2016-01-01

    Considering the emphasis of Islam on the importance of fasting, Muslims attempt to fast from dawn until sunset during the holy month of Ramadan. Fasting is associated with several benefits for normal and healthy individuals. However, it could pose high risks to the health of diabetic patients due to certain physiological changes. This study aimed to compare the physiological changes associated with fasting in healthy individuals and diabetic patients during Ramadan. Furthermore, we reviewed t...

  20. The prototype fast reactor

    Broomfield, A.M.

    1985-01-01

    The paper concerns the Prototype Fast Reactor (PFR), which is a liquid metal cooled fast reactor power station, situated at Dounreay, Scotland. The principal design features of a Fast Reactor and the PFR are given, along with key points of operating history, and health and safety features. The role of the PFR in the development programme for commercial reactors is discussed. (U.K.)

  1. The fast reactor

    1980-02-01

    The subject is discussed as follows: brief description of fast reactors; advantage in conserving uranium resources; experience, in UK and elsewhere, in fast reactor design, construction and operation; safety; production of plutonium, security aspects; consideration of future UK fast reactor programme. (U.K.)

  2. Ramadan, fasting and pregnancy

    Ahmed, Urfan Zahoor; Lykke, Jacob Alexander

    2014-01-01

    In Islam, the month of Ramadan is a period of fasting lasting 29 or 30 days. Epidemiological studies among Muslims in Denmark have not been conducted, but studies show, that fasting among pregnant Muslim women is common. Fasting does not increase the risk of growth restriction or preterm delivery...

  3. New perspective in the assessment of total intracellular magnesium

    Azzurra Sargenti

    2014-01-01

    Full Text Available Magnesium (Mg is essential for biological processes, but its cellular homeostasis has not been thoroughly elucidated, mainly because of the inadequacy of the available techniques to map intracellular Mg distribution. Recently, particular interest has been raised by a new family of fluorescent probes, diaza-18-crown-hydroxyquinoline (DCHQ, that shows remarkably high affinity and specificity for Mg, thus permitting the detection of the total intracellular Mg. The data obtained by fluori- metric and cytofluorimetric assays performed with DCHQ5 are in good agreement with atomic absorption spectroscopy, confirming that DCHQ5 probe allows both qualitative and quantitative determination of total intracellular Mg.

  4. Quantification of the Force of Nanoparticle-Cell Membrane Interactions and Its Influence on Intracellular Trafficking of Nanoparticles

    Vasir, Jaspreet K.; Labhasetwar, Vinod

    2008-01-01

    Understanding the interaction of nanoparticles (NPs) with the cell membrane and their trafficking through cells is imperative to fully explore the use of NPs for efficient intracellular delivery of therapeutics. Here, we report a novel method of measuring the force of NP-cell membrane interactions using atomic force microscopy (AFM). Poly(dl-lactide co-glycolide, PLGA) NPs functionalized with poly-l-lysine were used as a model system, to demonstrate that this force determines the adhesive interaction of NPs with the cell membrane and in turn the extent of cellular uptake of NPs, and hence that of the encapsulated therapeutic. Cellular uptake of NPs was monitored using AFM imaging, and the dynamics of their intracellular distribution was quantified using confocal microscopy. Results demonstrated that the functionalized NPs have a five-fold greater force of adhesion with the cell membrane and the time-lapse AFM images show their rapid internalization than unmodified NPs. The intracellular trafficking study showed that the functionalized NPs escape more rapidly and efficiently from late endosomes than unmodified NPs and result in 10-fold higher intracellular delivery of the encapsulated model protein. The findings described herein enhance our basic understanding of the NP-cell membrane interaction on the basis of physical phenomena that could have wider applications in developing efficient nanocarrier systems for intracellular delivery of therapeutics. PMID:18692238

  5. Involvement of intracellular Zn2+ signaling in LTP at perforant pathway-CA1 pyramidal cell synapse.

    Tamano, Haruna; Nishio, Ryusuke; Takeda, Atsushi

    2017-07-01

    Physiological significance of synaptic Zn 2+ signaling was examined at perforant pathway-CA1 pyramidal cell synapses. In vivo long-term potentiation (LTP) at perforant pathway-CA1 pyramidal cell synapses was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. Perforant pathway LTP was not attenuated under perfusion with CaEDTA (10 mM), an extracellular Zn 2+ chelator, but attenuated under perfusion with ZnAF-2DA (50 μM), an intracellular Zn 2+ chelator, suggesting that intracellular Zn 2+ signaling is required for perforant pathway LTP. Even in rat brain slices bathed in CaEDTA in ACSF, intracellular Zn 2+ level, which was measured with intracellular ZnAF-2, was increased in the stratum lacunosum-moleculare where perforant pathway-CA1 pyramidal cell synapses were contained after tetanic stimulation. These results suggest that intracellular Zn 2+ signaling, which originates in internal stores/proteins, is involved in LTP at perforant pathway-CA1 pyramidal cell synapses. Because the influx of extracellular Zn 2+ , which originates in presynaptic Zn 2+ release, is involved in LTP at Schaffer collateral-CA1 pyramidal cell synapses, synapse-dependent Zn 2+ dynamics may be involved in plasticity of postsynaptic CA1 pyramidal cells. © 2017 Wiley Periodicals, Inc.

  6. Ramadan, fasting and pregnancy

    Ahmed, Urfan Zahoor; Lykke, Jacob Alexander

    2014-01-01

    In Islam, the month of Ramadan is a period of fasting lasting 29 or 30 days. Epidemiological studies among Muslims in Denmark have not been conducted, but studies show, that fasting among pregnant Muslim women is common. Fasting does not increase the risk of growth restriction or preterm delivery......, but there are reports of decreased foetal movements. Furthermore, the fasting may have long-term health consequences for the offspring, especially when they reach their middle age. According to Islam and the interpretation, pregnant and breast-feeding women are allowed to postpone the fasting of the month of Ramadan...

  7. Ramadan, faste og graviditet

    Ahmed, Urfan Zahoor; Lykke, Jacob Alexander

    2014-01-01

    In Islam, the month of Ramadan is a period of fasting lasting 29 or 30 days. Epidemiological studies among Muslims in Denmark have not been conducted, but studies show, that fasting among pregnant Muslim women is common. Fasting does not increase the risk of growth restriction or preterm delivery......, but there are reports of decreased foetal movements. Furthermore, the fasting may have long-term health consequences for the offspring, especially when they reach their middle age. According to Islam and the interpretation, pregnant and breast-feeding women are allowed to postpone the fasting of the month of Ramadan...

  8. Fast Aerial Video Stitching

    Jing Li

    2014-10-01

    Full Text Available The highly efficient and robust stitching of aerial video captured by unmanned aerial vehicles (UAVs is a challenging problem in the field of robot vision. Existing commercial image stitching systems have seen success with offline stitching tasks, but they cannot guarantee high-speed performance when dealing with online aerial video sequences. In this paper, we present a novel system which has an unique ability to stitch high-frame rate aerial video at a speed of 150 frames per second (FPS. In addition, rather than using a high-speed vision platform such as FPGA or CUDA, our system is running on a normal personal computer. To achieve this, after the careful comparison of the existing invariant features, we choose the FAST corner and binary descriptor for efficient feature extraction and representation, and present a spatial and temporal coherent filter to fuse the UAV motion information into the feature matching. The proposed filter can remove the majority of feature correspondence outliers and significantly increase the speed of robust feature matching by up to 20 times. To achieve a balance between robustness and efficiency, a dynamic key frame-based stitching framework is used to reduce the accumulation errors. Extensive experiments on challenging UAV datasets demonstrate that our approach can break through the speed limitation and generate an accurate stitching image for aerial video stitching tasks.

  9. Fast isogeometric solvers for explicit dynamics

    Gao, Longfei

    2014-06-01

    In finite element analysis, solving time-dependent partial differential equations with explicit time marching schemes requires repeatedly applying the inverse of the mass matrix. For mass matrices that can be expressed as tensor products of lower dimensional matrices, we present a direct method that has linear computational complexity, i.e., O(N), where N is the total number of degrees of freedom in the system. We refer to these matrices as separable matrices. For non-separable mass matrices, we present a preconditioned conjugate gradient method with carefully designed preconditioners as an alternative. We demonstrate that these preconditioners, which are easy to construct and cheap to apply (O(N)), can deliver significant convergence acceleration. The performances of these preconditioners are independent of the polynomial order (p independence) and mesh resolution (h independence) for maximum continuity B-splines, as verified by various numerical tests. © 2014 Elsevier B.V.

  10. Intracellular performance of tailored nanoparticle tracers in magnetic particle imaging

    Arami, Hamed; Krishnan, Kannan M., E-mail: kannanmk@uw.edu [Department of Materials Science and Engineering, University of Washington, P.O. Box 352120, Seattle, Washington 98195-2120 (United States)

    2014-05-07

    Magnetic Particle Imaging (MPI) is a quantitative mass-sensitive, tracer-based imaging technique, with potential applications in various cellular imaging applications. The spatial resolution of MPI, in the first approximation, improves by decreasing the full width at half maximum (FWHM) of the field-derivative of the magnetization, dm/dH of the nanoparticle (NP) tracers. The FWHM of dm/dH depends critically on NPs’ size, size distribution, and their environment. However, there is limited information on the MPI performance of the NPs after their internalization into cells. In this work, 30 to 150 μg of the iron oxide NPs were incubated in a lysosome-like acidic buffer (0.2 ml, 20 mM citric acid, pH 4.7) and investigated by vibrating sample magnetometry, magnetic particle spectroscopy, transmission electron microscopy, and dynamic light scattering (DLS). The FWHM of the dm/dH curves of the NPs increased with incubation time and buffer to NPs ratio, consistent with a decrease in the median core size of the NPs from ∼20.1 ± 0.98 to ∼18.5 ± 3.15 nm. Further, these smaller degraded NPs formed aggregates that responded to the applied field by hysteretic reversal at higher field values and increased the FWHM. The rate of core size decrease and aggregation were inversely proportional to the concentration of the incubated NPs, due to their slower biodegradation kinetics. The results of this model experiment show that the MPI performance of the NPs in the acidic environments of the intracellular organelles (i.e., lysosomes and endosomes) can be highly dependent on their rate of internalization, residence time, and degradation.

  11. Modeling in fast dynamics of accidents in the primary circuit of PWR type reactors; Modelisation en dynamique rapide d'accidents dans le circuit primaire des reacteurs a eau pressurisee

    Robbe, M.F

    2003-12-01

    Two kinds of accidents, liable to occur in the primary circuit of a Pressurized Water Reactor and involving fast dynamic phenomena, are analyzed. The Loss Of Coolant Accident (LOCA) is the accident used to define the current PWR. It consists in a large-size break located in a pipe of the primary circuit. A blowdown wave propagates through the circuit. The pressure differences between the different zones of the reactor induce high stresses in the structures of the lower head and may degrade the reactor core. The primary circuit starts emptying from the break opening. Pressure decreases very quickly, involving a large steaming. Two thermal-hydraulic simulations of the blowdown phase of a LOCA are computed with the Europlexus code. The primary circuit is represented by a pipe-model including the hydraulic peculiarities of the circuit. The main differences between both computations concern the kind of reactor, the break location and model, and the initialization of the accidental operation. Steam explosion is a hypothetical severe accident liable to happen after a core melting. The molten part of the core (called corium) falls in the lower part of the reactor. The interaction between the hot corium and the cold water remaining at the bottom of the vessel induces a massive and violent vaporization of water, similar to an explosive phenomenon. A shock wave propagates in the vessel. what can damage seriously the neighbouring structures or drill the vessel. This work presents a synthesis of in-vessel parametrical studies carried out with the Europlexus code, the linkage of the thermal-hydraulic code Mc3d dedicated to the pre-mixing phase with the Europlexus code dealing with the explosion, and finally a benchmark between the Cigalon and Europlexus codes relative to the Vulcano mock-up. (author)

  12. Intracellular trafficking of new anticancer therapeutics: antibody–drug conjugates

    Kalim, Muhammad; Chen, Jie; Wang, Shenghao; Lin, Caiyao; Ullah, Saif; Liang, Keying; Ding, Qian; Chen, Shuqing; Zhan, Jinbiao

    2017-01-01

    Antibody–drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs. PMID:28814834

  13. Intracellular trafficking of new anticancer therapeutics: antibody-drug conjugates.

    Kalim, Muhammad; Chen, Jie; Wang, Shenghao; Lin, Caiyao; Ullah, Saif; Liang, Keying; Ding, Qian; Chen, Shuqing; Zhan, Jinbiao

    2017-01-01

    Antibody-drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs.

  14. EVIDENCE FOR THE MACROPHAGE INDUCING GENE IN MYCOBACTERIUM INTRACELLULARE

    Background: The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and possibly others. Organisms belonging to the MAC are phylogenetically closely related, opportunistic pathogens. The macrophage inducing gene (mig) is the only well-des...

  15. Imaging intracellular pH in live cells with a genetically encoded red fluorescent protein sensor.

    Tantama, Mathew; Hung, Yin Pun; Yellen, Gary

    2011-07-06

    Intracellular pH affects protein structure and function, and proton gradients underlie the function of organelles such as lysosomes and mitochondria. We engineered a genetically encoded pH sensor by mutagenesis of the red fluorescent protein mKeima, providing a new tool to image intracellular pH in live cells. This sensor, named pHRed, is the first ratiometric, single-protein red fluorescent sensor of pH. Fluorescence emission of pHRed peaks at 610 nm while exhibiting dual excitation peaks at 440 and 585 nm that can be used for ratiometric imaging. The intensity ratio responds with an apparent pK(a) of 6.6 and a >10-fold dynamic range. Furthermore, pHRed has a pH-responsive fluorescence lifetime that changes by ~0.4 ns over physiological pH values and can be monitored with single-wavelength two-photon excitation. After characterizing the sensor, we tested pHRed's ability to monitor intracellular pH by imaging energy-dependent changes in cytosolic and mitochondrial pH.

  16. Quantitative measurement of intracellular transport of nanocarriers by spatio-temporal image correlation spectroscopy

    Coppola, S; Pozzi, D; De Sanctis, S Candeloro; Caracciolo, G; Digman, M A; Gratton, E

    2013-01-01

    Spatio-temporal image correlation spectroscopy (STICS) is a powerful technique for assessing the nature of particle motion in complex systems although it has been rarely used to investigate the intracellular dynamics of nanocarriers so far. Here we introduce a method for characterizing the mode of motion of nanocarriers and for quantifying their transport parameters on different length scales from single-cell to subcellular level. Using this strategy we were able to study the mechanisms responsible for the intracellular transport of DOTAP–DOPC/DNA (DOTAP: 1,2-dioleoyl-3-trimethylammonium-propane; DOPC: dioleoylphosphocholine) and DC-Chol–DOPE/DNA (DC-Chol: 3β-[N-(N,N-dimethylaminoethane)-carbamoyl] cholesterol; DOPE: dioleoylphosphatidylethanolamine) lipoplexes in CHO-K1 (CHO: Chinese hamster ovary) live cells. Measurement of both diffusion coefficients and velocity vectors (magnitude and direction) averaged over regions of the cell revealed the presence of distinct modes of motion. Lipoplexes diffused slowly on the cell surface (diffusion coefficient: D ≈ 0.003 μm 2 s −1 ). In the cytosol, the lipoplexes’ motion was characterized by active transport with average velocity v ≈ 0.03 μm 2 s −1 and random motion. The method permitted us to generate an intracellular transport map showing several regions of concerted motion of lipoplexes. (paper)

  17. Quantitative measurement of intracellular transport of nanocarriers by spatio-temporal image correlation spectroscopy

    Coppola, S.; Pozzi, D.; Candeloro De Sanctis, S.; Digman, M. A.; Gratton, E.; Caracciolo, G.

    2013-03-01

    Spatio-temporal image correlation spectroscopy (STICS) is a powerful technique for assessing the nature of particle motion in complex systems although it has been rarely used to investigate the intracellular dynamics of nanocarriers so far. Here we introduce a method for characterizing the mode of motion of nanocarriers and for quantifying their transport parameters on different length scales from single-cell to subcellular level. Using this strategy we were able to study the mechanisms responsible for the intracellular transport of DOTAP-DOPC/DNA (DOTAP: 1,2-dioleoyl-3-trimethylammonium-propane; DOPC: dioleoylphosphocholine) and DC-Chol-DOPE/DNA (DC-Chol: 3β-[N-(N,N-dimethylaminoethane)-carbamoyl] cholesterol; DOPE: dioleoylphosphatidylethanolamine) lipoplexes in CHO-K1 (CHO: Chinese hamster ovary) live cells. Measurement of both diffusion coefficients and velocity vectors (magnitude and direction) averaged over regions of the cell revealed the presence of distinct modes of motion. Lipoplexes diffused slowly on the cell surface (diffusion coefficient: D ≈ 0.003 μm2 s-1). In the cytosol, the lipoplexes’ motion was characterized by active transport with average velocity v ≈ 0.03 μm2 s-1 and random motion. The method permitted us to generate an intracellular transport map showing several regions of concerted motion of lipoplexes.

  18. Data for automated, high-throughput microscopy analysis of intracellular bacterial colonies using spot detection

    Ernstsen, Christina Lundgaard; Login, Frédéric H.; Jensen, Helene Halkjær

    2017-01-01

    Quantification of intracellular bacterial colonies is useful in strategies directed against bacterial attachment, subsequent cellular invasion and intracellular proliferation. An automated, high-throughput microscopy-method was established to quantify the number and size of intracellular bacteria...

  19. Intracellular chemical gradients: morphing principle in bacteria

    Endres Robert G

    2012-09-01

    Full Text Available Abstract Advances in computational biology allow systematic investigations to ascertain whether internal chemical gradients can be maintained in bacteria – an open question at the resolution limit of fluorescence microscopy. While it was previously believed that the small bacterial cell size and fast diffusion in the cytoplasm effectively remove any such gradient, a new computational study published in BMC Biophysics supports the emerging view that gradients can exist. The study arose from the recent observation that phosphorylated CtrA forms a gradient prior to cell division in Caulobacter crescentus, a bacterium known for its complicated cell cycle. Tropini et al. (2012 postulate that such gradients can provide an internal chemical compass, directing protein localization, cell division and cell development. More specifically, they describe biochemical and physical constraints on the formation of such gradients and explore a number of existing bacterial cell morphologies. These chemical gradients may limit in vitro analyses, and may ensure timing control and robustness to fluctuations during critical stages in cell development.

  20. Intracellular sodium hydrogen exchange inhibition and clinical myocardial protection.

    Mentzer, Robert M; Lasley, Robert D; Jessel, Andreas; Karmazyn, Morris

    2003-02-01

    Although the mechanisms underlying ischemia/reperfusion injury remain elusive, evidence supports the etiologic role of intracellular calcium overload and oxidative stress induced by reactive oxygen species. Activation of the sodium hydrogen exchanger (NHE) is associated with intracellular calcium accumulation. Inhibition of the NHE-1 isoform may attenuate the consequences of this injury. Although there is strong preclinical and early clinical evidence that NHE inhibitors may be cardioprotective, definitive proof of this concept in humans awaits the results of ongoing clinical trials.