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Sample records for fast intracellular dynamics

  1. Intracellular Sterol Dynamics

    PubMed Central

    Mesmin, Bruno; Maxfield, Frederick R.

    2009-01-01

    We review the cellular mechanisms implicated in cholesterol trafficking and distribution. Recent studies have provided new information about the distribution of sterols within cells, including analysis of its transbilayer distribution. The cholesterol interaction with other lipids and its engagement in various trafficking processes will determine its proper level in a specific membrane; making the cholesterol distribution uneven among the various intracellular organelles. The cholesterol content is important since cholesterol plays an essential role in membranes by controlling their physicochemical properties as well as key cellular events such as signal transduction and protein trafficking. Cholesterol movement between cellular organelles is highly dynamic, and can be achieved by vesicular and non-vesicular processes. Various studies have analyzed the proteins that play a significant role in these processes, giving us new information about the relative importance of these two trafficking pathways in cholesterol transport. Although still poorly characterized in many trafficking routes, several potential sterol transport proteins have been described in detail; as a result, molecular mechanisms for sterol transport among membranes start to be appreciated. PMID:19286471

  2. Anomalous dynamics in intracellular transport

    NASA Astrophysics Data System (ADS)

    Dinner, Aaron

    2013-03-01

    This talk will describe quantitative analyses of particle tracking data for systems with cytoskeletally associated molecular motors to better understand the motions contributing to intracellular transport and, more generally, means for characterizing systems far from equilibrium. In particular, we have studied the motions of insulin-containing vesicles (granules) in a pancreatic beta cell line. We find subdiffusive behavior with correlations in both space and time. These data can be modeled by subordinating an ergodic random walk process to a non-ergodic one. We relate the dynamics to the underlying microtubule structure by imaging in the presence of the drug vinblastine. Our results provide a simple physical mechanism for how diverse pools of insulin granules and, in turn, biphasic secretion could arise. Time permitting, these dynamics will be compared with those of actomyosin assemblies.

  3. Adaptation of fast marching methods to intracellular signaling

    NASA Astrophysics Data System (ADS)

    Chikando, Aristide C.; Kinser, Jason M.

    2006-02-01

    Imaging of signaling phenomena within the intracellular domain is a well studied field. Signaling is the process by which all living cells communicate with their environment and with each other. In the case of signaling calcium waves, numerous computational models based on solving homogeneous reaction diffusion equations have been developed. Typically, the reaction diffusion approach consists of solving systems of partial differential equations at each update step. The traditional methods used to solve these reaction diffusion equations are very computationally expensive since they must employ small time steps in order to reduce the computational error. The presented research suggests the application of fast marching methods to imaging signaling calcium waves, more specifically fertilization calcium waves, in Xenopus laevis eggs. The fast marching approach provides fast and efficient means of tracking the evolution of monotonically advancing fronts. A model that employs biophysical properties of intracellular calcium signaling, and adapts fast marching methods to tracking the propagation of signaling calcium waves is presented. The developed model is used to reproduce simulation results obtained with reaction diffusion based model. Results obtained with our model agree with both the results obtained with reaction diffusion based models, and confocal microscopy observations during in vivo experiments. The adaptation of fast marching methods to intracellular protein or macromolecule trafficking is also briefly explored.

  4. BDI-modelling of complex intracellular dynamics.

    PubMed

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

    2008-03-07

    A BDI-based continuous-time modelling approach for intracellular dynamics is presented. It is shown how temporalized BDI-models make it possible to model intracellular biochemical processes as decision processes. By abstracting from some of the details of the biochemical pathways, the model achieves understanding in nearly intuitive terms, without losing veracity: classical intentional state properties such as beliefs, desires and intentions are founded in reality through precise biochemical relations. In an extensive example, the complex regulation of Escherichia coli vis-à-vis lactose, glucose and oxygen is simulated as a discrete-state, continuous-time temporal decision manager. Thus a bridge is introduced between two different scientific areas: the area of BDI-modelling and the area of intracellular dynamics.

  5. Intracellular Pressure Dynamics in Blebbing Cells.

    PubMed

    Strychalski, Wanda; Guy, Robert D

    2016-03-08

    Blebs are pressure-driven protrusions that play an important role in cell migration, particularly in three-dimensional environments. A bleb is initiated when the cytoskeleton detaches from the cell membrane, resulting in the pressure-driven flow of cytosol toward the area of detachment and local expansion of the cell membrane. Recent experiments involving blebbing cells have led to conflicting hypotheses regarding the timescale of intracellular pressure propagation. The interpretation of one set of experiments supports a poroelastic model of the cytoplasm that leads to slow pressure equilibration when compared to the timescale of bleb expansion. A different study concludes that pressure equilibrates faster than the timescale of bleb expansion. To address this discrepancy, a dynamic computational model of the cell was developed that includes mechanics of and the interactions among the cytoplasm, the actin cortex, the cell membrane, and the cytoskeleton. The model results quantify the relationship among cytoplasmic rheology, pressure, and bleb expansion dynamics, and provide a more detailed picture of intracellular pressure dynamics. This study shows the elastic response of the cytoplasm relieves pressure and limits bleb size, and that both permeability and elasticity of the cytoplasm determine bleb expansion time. Our model with a poroelastic cytoplasm shows that pressure disturbances from bleb initiation propagate faster than the timescale of bleb expansion and that pressure equilibrates slower than the timescale of bleb expansion. The multiple timescales in intracellular pressure dynamics explain the apparent discrepancy in the interpretation of experimental results.

  6. Dynamics of gradient formation by intracellular shuttling

    SciTech Connect

    Berezhkovskii, Alexander M.; Shvartsman, Stanislav Y.

    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.

  7. Spatiotemporal intracellular calcium dynamics during cardiac alternans

    PubMed Central

    Restrepo, Juan G.; Karma, Alain

    2009-01-01

    Cellular calcium transient alternans are beat-to-beat alternations in the peak cytosolic calcium concentration exhibited by cardiac cells during rapid electrical stimulation or under pathological conditions. Calcium transient alternans promote action potential duration alternans, which have been linked to the onset of life-threatening ventricular arrhythmias. Here we use a recently developed physiologically detailed mathematical model of ventricular myocytes to investigate both stochastic and deterministic aspects of intracellular calcium dynamics during alternans. The model combines a spatially distributed description of intracellular calcium cycling, where a large number of calcium release units are spatially distributed throughout the cell, with a full set of ionic membrane currents. The results demonstrate that ion channel stochasticity at the level of single calcium release units can influence the whole-cell alternans dynamics by causing phase reversals over many beats during fixed frequency pacing close to the alternans bifurcation. They also demonstrate the existence of a wide range of dynamical states. Depending on the sign and magnitude of calcium-voltage coupling, calcium alternans can be spatially synchronized or desynchronized, in or out of phase with action potential duration alternans, and the node separating out-of-phase regions of calcium alternans can be expelled from or trapped inside the cell. This range of states is found to be larger than previously anticipated by including a robust global attractor where calcium alternans can be spatially synchronized but out of phase with action potential duration alternans. The results are explained by a combined theoretical analysis of alternans stability and node motion using general iterative maps of the beat-to-beat dynamics and amplitude equations. PMID:19792040

  8. Intracellular dynamics with the phase microscope Airyscan

    NASA Astrophysics Data System (ADS)

    Tychinsky, Vladimir P.; Perevedentseva, Elena V.; Vyshenskaia, Tatiana V.; Kufal, Georgy E.

    1997-12-01

    Investigation of intracellular dynamics of Allium cepa inner epidermal cells are described. The applicability of the method for quantitative estimation of spatio-temporal phase fluctuations and the effect due to external factors is discussed. The analysis of time-sampled series allows one to detect the regions of various motility in cytoplasm. The intense Fourier-spectra harmonics in 0.2 - 8 Hz interval were observed inside a cell wall and cytoplasm. Regularly spaced 2- to 4-s long batches of 100-ms pulses at cell-wall sites are recorded. The phase-fluctuation intensity decreased and the frequencies of certain harmonics were shifted with lowering temperature. The advantages and specific features of the method are discussed.

  9. Cytoskeletal Network Morphology Regulates Intracellular Transport Dynamics.

    PubMed

    Ando, David; Korabel, Nickolay; Huang, Kerwyn Casey; Gopinathan, Ajay

    2015-10-20

    Intracellular transport is essential for maintaining proper cellular function in most eukaryotic cells, with perturbations in active transport resulting in several types of disease. Efficient delivery of critical cargos to specific locations is accomplished through a combination of passive diffusion and active transport by molecular motors that ballistically move along a network of cytoskeletal filaments. Although motor-based transport is known to be necessary to overcome cytoplasmic crowding and the limited range of diffusion within reasonable timescales, the topological features of the cytoskeletal network that regulate transport efficiency and robustness have not been established. Using a continuum diffusion model, we observed that the time required for cellular transport was minimized when the network was localized near the nucleus. In simulations that explicitly incorporated network spatial architectures, total filament mass was the primary driver of network transit times. However, filament traps that redirect cargo back to the nucleus caused large variations in network transport. Filament polarity was more important than filament orientation in reducing average transit times, and transport properties were optimized in networks with intermediate motor on and off rates. Our results provide important insights into the functional constraints on intracellular transport under which cells have evolved cytoskeletal structures, and have potential applications for enhancing reactions in biomimetic systems through rational transport network design.

  10. Intracellular dynamics of hippocampal place cells during virtual navigation

    PubMed Central

    Harvey, Christopher D.; Collman, Forrest; Dombeck, Daniel A.; Tank, David W.

    2009-01-01

    Hippocampal place cells encode spatial information in rate and temporal codes. To examine the mechanisms underlying hippocampal coding, we measured the intracellular dynamics of place cells by combining in vivo whole cell recordings with a virtual reality system. Head-restrained mice, running on a spherical treadmill, interacted with a computer-generated visual environment to perform spatial behaviors. Robust place cell activity was present during movement along a virtual linear track. From whole cell recordings, we identified three subthreshold signatures of place fields: (1) an asymmetric ramp-like depolarization of the baseline membrane potential; (2) an increase in the amplitude of intracellular theta oscillations; and, (3) a phase precession of the intracellular theta oscillation relative to the extracellularly-recorded theta rhythm. These intracellular dynamics underlie the primary features of place cell rate and temporal codes. The virtual reality system developed here will enable new experimental approaches to study the neural circuits underlying navigation. PMID:19829374

  11. Fluorescent acid-fast microscopy for measuring phagocytosis of Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum by Tetrahymena pyriformis and their intracellular growth.

    PubMed

    Strahl, E D; Gillaspy, G E; Falkinham, J O

    2001-10-01

    Fluorescent acid-fast microscopy (FAM) was used to enumerate intracellular Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum in the ciliated phagocytic protozoan Tetrahymena pyriformis. There was a linear relationship between FAM and colony counts of M. avium cells both from cultures and within protozoa. The Ziehl-Neelsen acid-fast stain could not be used to enumerate intracellular mycobacteria because uninfected protozoa contained acid-fast, bacterium-like particles. Starved, 7-day-old cultures of T. pyriformis transferred into fresh medium readily phagocytized M. avium, M. intracellulare, and M. scrofulaceum. Phagocytosis was rapid and reached a maximum in 30 min. M. avium, M. intracellulare, and M. scrofulaceum grew within T. pyriformis, increasing by factors of 4- to 40-fold after 5 days at 30 degrees C. Intracellular M. avium numbers remained constant over a 25-day period of growth (by transfer) of T. pyriformis. Intracellular M. avium cells also survived protozoan encystment and germination. The growth and viability of T. pyriformis were not affected by mycobacterial infection. The results suggest that free-living phagocytic protozoa may be natural hosts and reservoirs for M. avium, M. intracellulare, and M. scrofulaceum.

  12. Monitoring the intracellular calcium response to a dynamic hypertonic environment

    NASA Astrophysics Data System (ADS)

    Huang, Xiaowen; Yue, Wanqing; Liu, Dandan; Yue, Jianbo; Li, Jiaqian; Sun, Dong; Yang, Mengsu; Wang, Zuankai

    2016-03-01

    The profiling of physiological response of cells to external stimuli at the single cell level is of importance. Traditional approaches to study cell responses are often limited by ensemble measurement, which is challenging to reveal the complex single cell behaviors under a dynamic environment. Here we report the development of a simple microfluidic device to investigate intracellular calcium response to dynamic hypertonic conditions at the single cell level in real-time. Interestingly, a dramatic elevation in the intracellular calcium signaling is found in both suspension cells (human leukemic cell line, HL-60) and adherent cells (lung cancer cell line, A549), which is ascribed to the exposure of cells to the hydrodynamic stress. We also demonstrate that the calcium response exhibits distinct single cell heterogeneity as well as cell-type-dependent responses to the same stimuli. Our study opens up a new tool for tracking cellular activity at the single cell level in real time for high throughput drug screening.

  13. Probing intracellular dynamics in living cells with near-field optics.

    PubMed

    Bui, J D; Zelles, T; Lou, H J; Gallion, V L; Phillips, M I; Tan, W

    1999-07-01

    Near-field optics (NFO) overcomes the diffraction limit of light microscopes and permits visualization of single molecules. However, despite numerous applications of NFO in the physical sciences, there is still a paucity of applications in the neurosciences. In this work, the authors have developed NFO probes to image intracellular dynamic processes in living cells. This is the first time a NFO probe has been inserted inside a living cell to deliver light to a spatially controlled region for optical measurements and to record cellular responses to external stimuli. Two different optical detection systems (CCD camera and avalanche photon detection) were developed to monitor cellular responses to drug administration in two different cell types. NG108-15 neuroblastoma cells and vascular smooth muscle cells (VSMC) were penetrated with NFO probes. Intracellular Ca2+ increases post drug stimulation were detected by NFO probes. The cells were loaded with either fura-2/AM or fluo-3/AM calcium dyes. VSMC were stimulated with angiotensin II, resulting in a precise area of intracellular Ca2+ increase. Different response profiles of Ca2+ increases were observed after ionomycin and bradykinin administration in NG108-15 cells. Responsive heterogeneities due to ionomycin among different cells of the same type were recorded. The results show that NFO probes make possible real-time visualization of intracellular events. With refinement, intracellular NFO probes offer the potential of probing cell function with fast temporal and excellent spatial resolutions.

  14. Probing cytoskeleton dynamics by intracellular particle transport analysis

    NASA Astrophysics Data System (ADS)

    Götz, M.; Hodeck, K. F.; Witzel, P.; Nandi, A.; Lindner, B.; Heinrich, D.

    2015-07-01

    All cellular functions arise from the transport of molecules through a heterogeneous, highly dynamic cell interior for intracellular signaling. Here, the impact of intracellular architecture and cytoskeleton dynamics on transport processes is revealed by high-resolution single particle tracking within living cells, in combination with time-resolved local mean squared displacement (I-MSD) analysis. We apply the I-MSD analysis to trajectories of 200 nm silica particles within living cells of Dictyostelium discoideum obtained by high resolution spinning disc confocal microscopy with a frame rate of 100 fps and imaging in one fixed focal plane. We investigate phases of motor-driven active transport and subdiffusion, normal diffusion, as well as superdiffusion with high spatial and temporal resolution. Active directed intracellular motion is attributed to microtubule associated molecular motor driven transport with average absolute velocities of 2.8 μm s-1 for 200 nm diameter particles. Diffusion processes of these particles within wild-type cells are found to exhibit diffusion constants ranging across two orders of magnitude from subdiffusive to superdiffusive behavior. This type of analysis might prove of ample importance for medical applications, like targeted drug treatment of cells by nano-sized carriers or innovative diagnostic assays.

  15. Fast intracellular motion in the living cell by video rate reflection confocal laser scanning microscopy

    PubMed Central

    VESELY, PAVEL; BOYDE, ALAN

    2001-01-01

    Fast intracellular motion (FIM) was first revealed by back scattered light (BSL) imaging in video rate confocal scanning laser microscopy (VRCSLM), beyond the limits of spatial and temporal resolution obtainable with conventional optical microscopy. BSL imaging enabled visualisation of intra and extracellular motion with resolution in space down to 0.2 μm and in time to 1/25th of a second. Mapping the cell space at 0.2 μm×0.2 μm (XY = in instantaneous best focal plane)×0.5 μm (Z = height/depth, optic axis direction) volume steps revealed a communication layer above the known contact layer and an integrated dynamic spatial network (IDSN) towards the cell centre. FIM was originally observed as localised quasichaotic dancing (dithering) or reflecting patches/spots in the cell centre, faster in the darker nuclear space. Later, a second type of FIM was recognised which differed by the presence of a varied proportion of centrifugal and centripetal directional movements and/or jumping of patches/spots in the cell centre and outside the nuclear space. The first type is characteristic for cells in slightly adverse conditions while the second type has so far only been found in eutrophic cells. Temporal speeding up and coarsening of FIM, followed by slowing and eventually cessation at cell death, was found on exposure to strong stressors. It was concluded that the state of FIM provides instantaneous information about individual cell reactions to actual treatment and about cell survival. A putative switch between the first and second type FIM could be considered as an indicator of timing of cellular processes. The significance of FIM for the biology of the cell is seen in the rapid assessment of the condition of an individual live cell investigated by combination of various methods. Requirements for further development of this approach are outlined. PMID:11465857

  16. Cell fate reprogramming by control of intracellular network dynamics

    NASA Astrophysics Data System (ADS)

    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.

  17. Imaging intracellular RNA distribution and dynamics in living cells.

    PubMed

    Tyagi, Sanjay

    2009-05-01

    Powerful methods now allow the imaging of specific mRNAs in living cells. These methods enlist fluorescent proteins to illuminate mRNAs, use labeled oligonucleotide probes and exploit aptamers that render organic dyes fluorescent. The intracellular dynamics of mRNA synthesis, transport and localization can be analyzed at higher temporal resolution with these methods than has been possible with traditional fixed-cell or biochemical approaches. These methods have also been adopted to visualize and track single mRNA molecules in real time. This review explores the promises and limitations of these methods.

  18. Cell Fate Reprogramming by Control of Intracellular Network Dynamics

    PubMed Central

    Zañudo, Jorge G. T.; Albert, Réka

    2015-01-01

    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. Here we develop a novel network control framework that integrates the structural and functional information available for intracellular networks to predict control targets. Formulated in a logical dynamic scheme, our approach drives any initial state to the target state with 100% effectiveness and needs to be applied only transiently for the network 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 helper 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. PMID:25849586

  19. Fast internal dynamics in alcohol dehydrogenase

    SciTech Connect

    Monkenbusch, M.; Stadler, A. Biehl, R.; Richter, D.; Ollivier, J.; Zamponi, M.

    2015-08-21

    Large-scale domain motions in alcohol dehydrogenase (ADH) have been observed previously by neutron spin-echo spectroscopy (NSE). We have extended the investigation on the dynamics of ADH in solution by using high-resolution neutron time-of-flight (TOF) and neutron backscattering (BS) spectroscopy in the incoherent scattering range. The observed hydrogen dynamics were interpreted in terms of three mobility classes, which allowed a simultaneous description of the measured TOF and BS spectra. In addition to the slow global protein diffusion and domain motions observed by NSE, a fast internal process could be identified. Around one third of the protons in ADH participate in the fast localized diffusive motion. The diffusion coefficient of the fast internal motions is around two third of the value of the surrounding D{sub 2}O solvent. It is tempting to associate the fast internal process with solvent exposed amino acid residues with dangling side chains.

  20. Fast Parallel Computation Of Multibody Dynamics

    NASA Technical Reports Server (NTRS)

    Fijany, Amir; Kwan, Gregory L.; Bagherzadeh, Nader

    1996-01-01

    Constraint-force algorithm fast, efficient, parallel-computation algorithm for solving forward dynamics problem of multibody system like robot arm or vehicle. Solves problem in minimum time proportional to log(N) by use of optimal number of processors proportional to N, where N is number of dynamical degrees of freedom: in this sense, constraint-force algorithm both time-optimal and processor-optimal parallel-processing algorithm.

  1. Global intracellular slow-wave dynamics of the thalamocortical system.

    PubMed

    Sheroziya, Maxim; Timofeev, Igor

    2014-06-25

    It is widely accepted that corticothalamic neurons recruit the thalamus in slow oscillation, but global slow-wave thalamocortical dynamics have never been experimentally shown. We analyzed intracellular activities of neurons either from different cortical areas or from a variety of specific and nonspecific thalamic nuclei in relation to the phase of global EEG signal in ketamine-xylazine anesthetized mice. We found that, on average, slow-wave active states started off within frontal cortical areas as well as higher-order and intralaminar thalamus (posterior and parafascicular nuclei) simultaneously. Then, the leading edge of active states propagated in the anteroposterior/lateral direction over the cortex at ∼40 mm/s. The latest structure we recorded within the slow-wave cycle was the anterior thalamus, which followed active states of the retrosplenial cortex. Active states from different cortical areas tended to terminate simultaneously. Sensory thalamic ventral posterior medial and lateral geniculate nuclei followed cortical active states with major inhibitory and weak tonic-like "modulator" EPSPs. In these nuclei, sharp-rising, large-amplitude EPSPs ("drivers") were not modulated by cortical slow waves, suggesting their origin in ascending pathways. The thalamic active states in other investigated nuclei were composed of depolarization: some revealing "driver"- and "modulator"-like EPSPs, others showing "modulator"-like EPSPs only. We conclude that sensory thalamic nuclei follow the propagating cortical waves, whereas neurons from higher-order thalamic nuclei display "hub dynamics" and thus may contribute to the generation of cortical slow waves.

  2. Biomechanics and Intracellular Dynamics of Vascular Endothelial Cells

    NASA Astrophysics Data System (ADS)

    Ou-Yang, H. Daniel

    2004-03-01

    Understanding the internal mechanical properties of living cells is essential to gain insight to basic cellular functions ranging from cellular signal transduction, intracellular traffics to cell motility. Vascular endothelial cells form a single cell layer that lines all blood vessels and serves to regulate exchanges between the blood stream and the surrounding tissues. Endothelial cells are one of the most studied cell types because of their roles in cardiovascular diseases and the linkage between their growth control and strategies of cancer treatments. This talk reports the application of a novel methodology by which scientists can explore cellular functions and study cytoskeleton dynamics of living cells at the subcellular level with minimal invasion. The methodology is based on the realization that optical tweezers can be used to measure the mechanical properties of the cytoskeleton in the vicinity of organelles and cellular structures. Optical tweezers is a technique based on the physics that dielectric materials, such as silica beads, latex particles or protein aggregates are attracted to and thus trapped at the focal point of a tightly focused laser beam in an aqueous medium. It has been shown that viscoelasticity can be determined from the movements of the trapped object in an oscillating optical tweezers. Applying the oscillating tweezers to intracellular cellular structures, we were able to determine the frequency dependent mechanical properties of the interior of cultured bovine endothelial cells. In contrast to the viscoelastic behavior expected of a network of cytoskelatal proteins, we found unusually large fluctuations in both elastic and loss moduli of the cell interior. More surprisingly, both mechanical moduli showed rhythmic behavior with a periodicity in the range of 20 - 30 seconds in healthy living cells. The rhythm could be altered by drug treatments, and the amplitude of the fluctuations diminished when cells were depleted of nutrients

  3. Fasting and postprandial regulation of the intracellular localization of adiponectin and of adipokines secretion by dietary fat in rats

    PubMed Central

    Olivares-García, V; Torre-Villalvazo, I; Velázquez-Villegas, L; Alemán, G; Lara, N; López-Romero, P; Torres, N; Tovar, A R; Díaz-Villaseñor, A

    2015-01-01

    Background/Objective: Dietary fat sources modulate fasting serum concentration of adipokines, particularly adiponectin. However, previous studies utilized obese animals in which adipose tissue function is severely altered. Thus, the present study aimed to assess the postprandial regulation of adipokine secretion in nonobese rats that consumed high-fat diet (HFD) composed of different types of fat for a short time. Methods: The rats were fed a control diet or a HFD containing coconut, safflower or soybean oil (rich in saturated fatty acid, monounsaturated fatty acid or polyunsaturated fatty acid, respectively) for 21 days. The serum concentrations of adiponectin, leptin, retinol, retinol-binding protein-4 (RBP-4), visfatin and resistin were determined at fasting and after refeeding. Adiponectin multimerization and intracellular localization, as well as the expression of endoplasmic reticulum (ER) chaperones and transcriptional regulators, were evaluated in epididymal white adipose tissue. Results: In HFD-fed rats, serum adiponectin was significantly decreased 30 min after refeeding. With coconut oil, all three multimeric forms were reduced; with safflower oil, only the high-molecular-weight (HMW) and medium-molecular-weight (MMW) forms were decreased; and with soybean oil, only the HMW form was diminished. These reductions were due not to modifications in mRNA abundance or adiponectin multimerization but rather to an increment in intracellular localization at the ER and plasma membrane. Thus, when rats consumed a HFD, the type of dietary fat differentially affected the abundance of endoplasmic reticulum resident protein 44 kDa (ERp44), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ (PPARγ) mRNAs, all of which are involved in the post-translational processing of adiponectin required for its secretion. Leptin, RBP-4, resistin and visfatin serum concentrations did not change during fasting, whereas modest alterations were observed after

  4. The dynamics of fast metal forming processes

    NASA Astrophysics Data System (ADS)

    Tirosh, J.; Iddan, D.

    1994-04-01

    THIS WORK PRESENTS a procedure to assess, by an approximate lower bound, the dynamic stress distribution that prevails in the deforming zone during fast forming processes. An objective measure to what is "a fast process" will be determined by the magnitude of three dimensionless groups which characterize dynamic plasticity. The suggested generalization of the lower bound calls for admissible trials of "dynamic stress" solutions for rigid-plastic and, possibly, viscoplastic materials. The analysis becomes a rigorous lower bound as the speed approaches zero. Otherwise, it elevates the true bound with quantified speed-dependent terms associated with the above groups. Applications are demonstrated via examples. Technological limitations imposed by the high speed are indicated. Experimental data and/or numerical solutions are added for comparisons whenever these exist.

  5. Controlling fast chaos in delay dynamical systems.

    PubMed

    Blakely, Jonathan N; Illing, Lucas; Gauthier, Daniel J

    2004-05-14

    We introduce a novel approach for controlling fast chaos in time-delay dynamical systems and use it to control a chaotic photonic device with a characteristic time scale of approximately 12 ns. Our approach is a prescription for how to implement existing chaos-control algorithms in a way that exploits the system's inherent time delay and allows control even in the presence of substantial control-loop latency (the finite time it takes signals to propagate through the components in the controller). This research paves the way for applications exploiting fast control of chaos, such as chaos-based communication schemes and stabilizing the behavior of ultrafast lasers.

  6. Imaging intracellular protein dynamics by spinning disk confocal microscopy

    PubMed Central

    Stehbens, Samantha; Pemble, Hayley; Murrow, Lindsay; Wittmann, Torsten

    2012-01-01

    The palette of fluorescent proteins has grown exponentially over the last decade, and as a result live imaging of cells expressing fluorescently tagged proteins is becoming more and more main stream. Spinning disk confocal microscopy (SDC) is a high speed optical sectioning technique, and a method of choice to observe and analyze intracellular fluorescent protein dynamics at high spatial and temporal resolution. In an SDC system, a rapidly rotating pinhole disk generates thousands of points of light that scan the specimen simultaneously, which allows direct capture of the confocal image with low noise scientific grade cooled charged-coupled device (CCD) cameras, and can achieve frame rates of up 1000 frames per second. In this chapter we describe important components of a state-of-the-art spinning disk system optimized for live cell microscopy, and provide a rationale for specific design choices. We also give guidelines how other imaging techniques such as total internal reflection (TIRF) microscopy or spatially controlled photoactivation can be coupled with SDC imaging, and provide a short protocol on how to generate cell lines stably expressing fluorescently tagged proteins by lentivirus-mediated transduction. PMID:22264541

  7. Systematic Characterization of Dynamic Parameters of Intracellular Calcium Signals

    PubMed Central

    Mackay, Laurent; Mikolajewicz, Nicholas; Komarova, Svetlana V.; Khadra, Anmar

    2016-01-01

    Dynamic processes, such as intracellular calcium signaling, are hallmark of cellular biology. As real-time imaging modalities become widespread, a need for analytical tools to reliably characterize time-series data without prior knowledge of the nature of the recordings becomes more pressing. The goal of this study is to develop a signal-processing algorithm for MATLAB that autonomously computes the parameters characterizing prominent single transient responses (TR) and/or multi-peaks responses (MPR). The algorithm corrects for signal contamination and decomposes experimental recordings into contributions from drift, TRs, and MPRs. It subsequently provides numerical estimates for the following parameters: time of onset after stimulus application, activation time (time for signal to increase from 10 to 90% of peak), and amplitude of response. It also provides characterization of the (i) TRs by quantifying their area under the curve (AUC), response duration (time between 1/2 amplitude on ascent and descent of the transient), and decay constant of the exponential decay region of the deactivation phase of the response, and (ii) MPRs by quantifying the number of peaks, mean peak magnitude, mean periodicity, standard deviation of periodicity, oscillatory persistence (time between first and last discernable peak), and duty cycle (fraction of period during which system is active) for all the peaks in the signal, as well as coherent oscillations (i.e., deterministic spikes). We demonstrate that the signal detection performance of this algorithm is in agreement with user-mediated detection and that parameter estimates obtained manually and algorithmically are correlated. We then apply this algorithm to study how metabolic acidosis affects purinergic (P2) receptor-mediated calcium signaling in osteoclast precursor cells. Our results reveal that acidosis significantly attenuates the amplitude and AUC calcium responses at high ATP concentrations. Collectively, our data

  8. Fast dynamic processes of solar radiation

    SciTech Connect

    Tomson, Teolan

    2010-02-15

    This paper studies dynamic processes of fast-alternating solar radiation which are assessed by alternation of clouds. Most attention is devoted to clouds of type Cumulus Humilis, identified through visual recognition and/or a specially constructed automatic sensor. One second sampling period was used. Recorded data series were analyzed with regard to duration of illuminated 'windows' between shadows, their stochastic intervals, fronts and the magnitude of increments of solar irradiance. (author)

  9. Fast Parallel Computation Of Manipulator Inverse Dynamics

    NASA Technical Reports Server (NTRS)

    Fijany, Amir; Bejczy, Antal K.

    1991-01-01

    Method for fast parallel computation of inverse dynamics problem, essential for real-time dynamic control and simulation of robot manipulators, undergoing development. Enables exploitation of high degree of parallelism and, achievement of significant computational efficiency, while minimizing various communication and synchronization overheads as well as complexity of required computer architecture. Universal real-time robotic controller and simulator (URRCS) consists of internal host processor and several SIMD processors with ring topology. Architecture modular and expandable: more SIMD processors added to match size of problem. Operate asynchronously and in MIMD fashion.

  10. Global Intracellular Slow-Wave Dynamics of the Thalamocortical System

    PubMed Central

    Sheroziya, Maxim

    2014-01-01

    It is widely accepted that corticothalamic neurons recruit the thalamus in slow oscillation, but global slow-wave thalamocortical dynamics have never been experimentally shown. We analyzed intracellular activities of neurons either from different cortical areas or from a variety of specific and nonspecific thalamic nuclei in relation to the phase of global EEG signal in ketamine-xylazine anesthetized mice. We found that, on average, slow-wave active states started off within frontal cortical areas as well as higher-order and intralaminar thalamus (posterior and parafascicular nuclei) simultaneously. Then, the leading edge of active states propagated in the anteroposterior/lateral direction over the cortex at ∼40 mm/s. The latest structure we recorded within the slow-wave cycle was the anterior thalamus, which followed active states of the retrosplenial cortex. Active states from different cortical areas tended to terminate simultaneously. Sensory thalamic ventral posterior medial and lateral geniculate nuclei followed cortical active states with major inhibitory and weak tonic-like “modulator” EPSPs. In these nuclei, sharp-rising, large-amplitude EPSPs (“drivers”) were not modulated by cortical slow waves, suggesting their origin in ascending pathways. The thalamic active states in other investigated nuclei were composed of depolarization: some revealing “driver”- and “modulator”-like EPSPs, others showing “modulator”-like EPSPs only. We conclude that sensory thalamic nuclei follow the propagating cortical waves, whereas neurons from higher-order thalamic nuclei display “hub dynamics” and thus may contribute to the generation of cortical slow waves. PMID:24966387

  11. Geometrical shock dynamics of fast magnetohydrodynamic shocks

    NASA Astrophysics Data System (ADS)

    Mostert, Wouter; Pullin, Dale I.; Samtaney, Ravi; Wheatley, Vincent

    2016-11-01

    We extend the theory of geometrical shock dynamics (GSD, Whitham 1958), to two-dimensional fast magnetohydrodynamic (MHD) shocks moving in the presence of nonuniform magnetic fields of general orientation and strength. The resulting generalized area-Mach number rule is adapted to MHD shocks moving in two spatial dimensions. A partially-spectral numerical scheme developed from that of Schwendeman (1993) is described. This is applied to the stability of plane MHD fast shocks moving into a quiescent medium containing a uniform magnetic field whose field lines are inclined to the plane-shock normal. In particular, we consider the time taken for an initially planar shock subject to an initial perturbed magnetosonic Mach number distribution, to first form shock-shocks. Supported by KAUST OCRF Award No. URF/1/2162-01.

  12. Monitoring intracellular oxidative events using dynamic spectral unmixing microscopy

    EPA Science Inventory

    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...

  13. Dynamic Reorganization of Metabolic Enzymes into Intracellular Bodies

    PubMed Central

    O’Connell, Jeremy D.; Zhao, Alice; Ellington, Andrew D.; Marcotte, Edward M.

    2013-01-01

    Both focused and large-scale cell biological and biochemical studies have revealed that hundreds of metabolic enzymes across diverse organisms form large intracellular bodies. These proteinaceous bodies range in form from fibers and intracellular foci—such as those formed by enzymes of nitrogen and carbon utilization and of nucleotide biosynthesis—to high-density packings inside bacterial microcompartments and eukaryotic microbodies. Although many enzymes clearly form functional mega-assemblies, it is not yet clear for many recently discovered cases whether they represent functional entities, storage bodies, or aggregates. In this article, we survey intracellular protein bodies formed by metabolic enzymes, asking when and why such bodies form and what their formation implies for the functionality—and dysfunctionality—of the enzymes that comprise them. The panoply of intracellular protein bodies also raises interesting questions regarding their evolution and maintenance within cells. We speculate on models for how such structures form in the first place and why they may be inevitable. PMID:23057741

  14. A Dynamic Management Method for Fast Manufacturing Resource Reconfiguration

    NASA Astrophysics Data System (ADS)

    Yuan, Zhiye

    To fast and optimally reconfigure manufacturing resource, a dynamic management method for fast manufacturing resource reconfiguration based on holon was proposed. In this method, a dynamic management structure for fast manufacturing resource reconfiguration was established based on holon. Moreover, the cooperation relationship among holons for fast manufacturing resource reconfiguration and the manufacturing information cooperation mechanism based on holonic were constructed. Finally, the simulation system of a dynamic management method for fast manufacturing resource reconfiguration was demonstrated and validated by Flexsim software. It has shown the proposed method can dynamically and optimally reconfigure manufacturing resource, and it can effectively improve the efficiency of manufacturing processes.

  15. Fast Fourier transform discrete dislocation dynamics

    NASA Astrophysics Data System (ADS)

    Graham, J. T.; Rollett, A. D.; LeSar, R.

    2016-12-01

    Discrete dislocation dynamics simulations have been generally limited to modeling systems described by isotropic elasticity. Effects of anisotropy on dislocation interactions, which can be quite large, have generally been ignored because of the computational expense involved when including anisotropic elasticity. We present a different formalism of dislocation dynamics in which the dislocations are represented by the deformation tensor, which is a direct measure of the slip in the lattice caused by the dislocations and can be considered as an eigenstrain. The stresses arising from the dislocations are calculated with a fast Fourier transform (FFT) method, from which the forces are determined and the equations of motion are solved. Use of the FFTs means that the stress field is only available at the grid points, which requires some adjustments/regularizations to be made to the representation of the dislocations and the calculation of the force on individual segments, as is discussed hereinafter. A notable advantage of this approach is that there is no computational penalty for including anisotropic elasticity. We review the method and apply it in a simple dislocation dynamics calculation.

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

    NASA Astrophysics Data System (ADS)

    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.

  17. Fast, Ultrasensitive Detection of Reactive Oxygen Species Using a Carbon Nanotube Based-Electrocatalytic Intracellular Sensor

    PubMed Central

    2015-01-01

    Herein, we report a highly sensitive electrocatalytic sensor-cell construct that can electrochemically communicate with the internal environment of immune cells (e.g., macrophages) via the selective monitoring of a particular reactive oxygen species (ROS), hydrogen peroxide. The sensor, which is based on vertically aligned single-walled carbon nanotubes functionalized with an osmium electrocatalyst, enabled the unprecedented detection of a local intracellular “pulse” of ROS on a short second time scale in response to bacterial endotoxin (lipopolysaccharide-LPS) stimulation. Our studies have shown that this initial pulse of ROS is dependent on NADPH oxidase (NOX) and toll like receptor 4 (TLR4). The results suggest that bacteria can induce a rapid intracellular pulse of ROS in macrophages that initiates the classical innate immune response of these cells to infection. PMID:26438964

  18. Optical imaging of fast, dynamic neurophysiological function.

    SciTech Connect

    Rector, D. M.; Carter, K. M.; Yao, X.; George, J. S.

    2002-01-01

    Fast evoked responses were imaged from rat dorsal medulla and whisker barrel cortex. To investigate the biophysical mechanisms involved, fast optical responses associated with isolated crustacean nerve stimulation were recorded using birefringence and scattered light. Such studies allow optimization of non-invasive imaging techniques being developed for use in humans.

  19. Use of Stable Isotopes to Follow Intracellular Water Dynamics in Living Cells

    SciTech Connect

    Kreuzer, Helen W.; Hegg, Eric L.

    2012-01-28

    Despite the importance of water to cell structure and function, intracellular water dynamics are poorly understood. A new method based on isotope ratio measurements has revealed that a substantial portion of the O and H atoms in the intracellular water of rapidly-dividing cultured cells is derived from metabolic activity, and not from environmental water. These findings have led to a dynamic model of intracellular water composition: (1) Intracellular water is composed of water that diffuses in from the extracellular environment and water that is created as a result of metabolic activity. (2) The relative amounts of environmental and metabolic water inside a cell are a function of the cell's metabolic activity. (3) The oxygen and hydrogen isotope ratios of cellular metabolites are a function of those of intracellular water, and therefore reflect the metabolic activity of the cell at the time of biosynthesis. Data from gram-positive and gram-negative bacteria as well as cultured mammalian cells are consistent with the model.

  20. Hydrophilic trans-Cyclooctenylated Noncanonical Amino Acids for Fast Intracellular Protein Labeling.

    PubMed

    Kozma, Eszter; Nikić, Ivana; Varga, Balázs R; Aramburu, Iker Valle; Kang, Jun Hee; Fackler, Oliver T; Lemke, Edward A; Kele, Péter

    2016-08-17

    Introduction of bioorthogonal functionalities (e.g., trans-cyclooctene-TCO) into a protein of interest by site-specific genetic encoding of non-canonical amino acids (ncAAs) creates uniquely targetable platforms for fluorescent labeling schemes in combination with tetrazine-functionalized dyes. However, fluorescent labeling of an intracellular protein is usually compromised by high background, arising from the hydrophobicity of ncAAs; this is typically compensated for by hours-long washout to remove excess ncAAs from the cellular interior. To overcome these problems, we designed, synthesized, and tested new, hydrophilic TCO-ncAAs. One derivative, DOTCO-lysine was genetically incorporated into proteins with good yield. The increased hydrophilicity shortened the excess ncAA washout time from hours to minutes, thus permitting rapid labeling and subsequent fluorescence microscopy.

  1. Extrinsic periodic information interpolates between monostable and bistable states in intracellular calcium dynamics

    NASA Astrophysics Data System (ADS)

    Lin, Ling; Duan, Wei-Long

    2015-06-01

    Extrinsic periodic information including physiological cyclical and circadian replacement would affect inevitably a real cell, in this paper we investigate the effect of extrinsic periodic information on intracellular calcium dynamics by means of second-order algorithm for stochastic simulation colored noises. By simulating time evolutions and stationary probability distribution of intracellular Ca2+ concentrations, the results show: (i) intracellular calcium oscillation between cytosol and calcium store shows synchronous and anti-synchronous oscillation as intensity and frequency of extrinsic periodic information vary; (ii) extrinsic periodic information interpolates stability from bistable state → monostable state → bistable state → monostable state as frequency of extrinsic periodic information increases; (iii) extrinsic periodic information interpolates stability from monostable state → bistable state as intensity of extrinsic periodic information increases.

  2. Microscopy tools for the investigation of intracellular lipid storage and dynamics

    PubMed Central

    Daemen, Sabine; van Zandvoort, Marc A.M.J.; Parekh, Sapun H.; Hesselink, Matthijs K.C.

    2015-01-01

    Background Excess storage of lipids in ectopic tissues, such as skeletal muscle, liver, and heart, seems to associate closely with metabolic abnormalities and cardiac disease. Intracellular lipid storage occurs in lipid droplets, which have gained attention as active organelles in cellular metabolism. Recent developments in high-resolution microscopy and microscopic spectroscopy have opened up new avenues to examine the physiology and biochemistry of intracellular lipids. Scope of review The aim of this review is to give an overview of recent technical advances in microscopy, and its application for the visualization, identification, and quantification of intracellular lipids, with special focus to lipid droplets. In addition, we attempt to summarize the probes currently available for the visualization of lipids. Major conclusions The continuous development of lipid probes in combination with the rapid development of microscopic techniques can provide new insights in the role and dynamics of intracellular lipids. Moreover, in situ identification of intracellular lipids is now possible and promises to add a new dimensionality to analysis of lipid biochemistry, and its relation to (patho)physiology. PMID:26977387

  3. Intracellular regulation of protein degradation during sepsis is different in fast- and slow-twitch muscle.

    PubMed

    Tiao, G; Lieberman, M; Fischer, J E; Hasselgren, P O

    1997-03-01

    We tested the hypothesis that the difference in the response to sepsis of protein breakdown between fast- and slow-twitch skeletal muscle reflects differential activation of the energy-ubiquitin-dependent proteolytic pathway. In addition, we defined the time course and the tissue specificity of sepsis-induced changes in the expression of the ubiquitin pathway. Sepsis was induced in rats by cecal ligation and puncture; control rats were sham operated. Energy-dependent protein breakdown was measured in incubated extensor digitorum longus (EDL) and soleus muscles. Ubiquitin mRNA levels were determined by Northern blot analysis. Sepsis resulted in increased energy-dependent protein breakdown and upregulated expression of ubiquitin mRNA in the fast-twitch EDL but not in the slow-twitch soleus muscle. The sepsis-induced increase in ubiquitin mRNA levels in the EDL muscle was noticeable before the increase in energy-dependent protein breakdown. Sepsis increased ubiquitin mRNA levels in the diaphragm (a mixed fiber-type muscle) but not in heart, liver, kidney, or intestine, consistent with a tissue-specific regulation of the ubiquitin system during sepsis. The results suggest that the difference in protein breakdown during sepsis between fast- and slow-twitch muscles reflects differential activation of the energy-ubiquitin-dependent proteolytic pathway. The data also suggest that the expression of the ubiquitin pathway is upregulated in a time-dependent fashion during sepsis and that this response is not a generalized phenomenon but is tissue specific.

  4. A fast and specific method to screen for intracellular amyloid inhibitors using bacterial model systems.

    PubMed

    Navarro, Susanna; Carija, Anita; Muñoz-Torrero, Diego; Ventura, Salvador

    2016-10-04

    The aggregation of a large variety of amyloidogenic proteins is linked to the onset of devastating human disorders. Therefore, there is an urgent need for effective molecules able to modulate the aggregative properties of these polypeptides in their natural environment, in order to prevent, delay or halt the progression of such diseases. On the one hand, the complexity and cost of animal models make them inefficient at early stages of drug discovery, where large chemical libraries are usually screened. On the other hand, in vitro aggregation assays in aqueous solutions hardly reproduce (patho)physiological conditions. In this context, because the formation of insoluble aggregates in bacteria shares mechanistic and functional properties with amyloid self-assembly in higher organisms, they have emerged as a promising system to model aggregation in the cell. Here we show that bacteria provide a powerful and cost-effective system to screen for amyloid inhibitors using fluorescence spectroscopy and flow cytometry, thanks to the ability of the novel red fluorescent ProteoStat dye to detect specifically intracellular amyloid-like aggregates. We validated the approach using the Alzheimer's linked Aβ40 and Aβ42 peptides and tacrine- and huprine-based aggregation inhibitors. Overall, the present method bears the potential to replace classical in vitro anti-aggregation assays.

  5. PERK regulates Gq protein-coupled intracellular Ca(2+) dynamics in primary cortical neurons.

    PubMed

    Zhu, Siying; McGrath, Barbara C; Bai, Yuting; Tang, Xin; Cavener, Douglas R

    2016-10-01

    PERK (EIF2AK3) is an ER-resident eIF2α kinase required for behavioral flexibility and metabotropic glutamate receptor-dependent long-term depression via its translational control. Motivated by the recent discoveries that PERK regulates Ca(2+) dynamics in insulin-secreting β-cells underlying glucose-stimulated insulin secretion, and modulates Ca(2+) signals-dependent working memory, we explored the role of PERK in regulating Gq protein-coupled Ca(2+) dynamics in pyramidal neurons. We found that acute PERK inhibition by the use of a highly specific PERK inhibitor reduced the intracellular Ca(2+) rise stimulated by the activation of acetylcholine, metabotropic glutamate and bradykinin-2 receptors in primary cortical neurons. More specifically, acute PERK inhibition increased IP3 receptor mediated ER Ca(2+) release, but decreased receptor-operated extracellular Ca(2+) influx. Impaired Gq protein-coupled intracellular Ca(2+) rise was also observed in genetic Perk knockout neurons. Taken together, our findings reveal a novel role of PERK in neurons, which is eIF2α-independent, and suggest that the impaired working memory in forebrain-specific Perk knockout mice may stem from altered Gq protein-coupled intracellular Ca(2+) dynamics in cortical pyramidal neurons.

  6. Fast dynamics for atoms in optical lattices.

    PubMed

    Łącki, Mateusz; Zakrzewski, Jakub

    2013-02-08

    Cold atoms in optical lattices allow for accurate studies of many body dynamics. Rapid time-dependent modifications of optical lattice potentials may result in significant excitations in atomic systems. The dynamics in such a case is frequently quite incompletely described by standard applications of tight-binding models (such as, e.g., Bose-Hubbard model or its extensions) that typically neglect the effect of the dynamics on the transformation between the real space and the tight-binding basis. We illustrate the importance of a proper quantum mechanical description using a multiband extended Bose-Hubbard model with time-dependent Wannier functions. We apply it to situations directly related to experiments.

  7. Intracellular delivery and trafficking dynamics of a lymphoma-targeting antibody-polymer conjugate.

    PubMed

    Berguig, Geoffrey Y; Convertine, Anthony J; Shi, Julie; Palanca-Wessels, Maria Corinna; Duvall, Craig L; Pun, Suzie H; Press, Oliver W; Stayton, Patrick S

    2012-12-03

    Ratiometric fluorescence and cellular fractionation studies were employed to characterize the intracellular trafficking dynamics of antibody-poly(propylacrylic acid) (PPAA) conjugates in CD22+ RAMOS-AW cells. The HD39 monoclonal antibody (mAb) directs CD22-dependent, receptor-mediated uptake in human B-cell lymphoma cells, where it is rapidly trafficked to the lysosomal compartment. To characterize the intracellular-release dynamics of the polymer-mAb conjugates, HD39-streptavidin (HD39/SA) was dual-labeled with pH-insensitive Alexa Fluor 488 and pH-sensitive pHrodo fluorophores. The subcellular pH distribution of the HD39/SA-polymer conjugates was quantified as a function of time by live-cell fluorescence microscopy, and the average intracellular pH value experienced by the conjugates was also characterized as a function of time by flow cytometry. PPAA was shown to alter the intracellular trafficking kinetics strongly relative to HD39/SA alone or HD39/SA conjugates with a control polymer, poly(methacryclic acid) (PMAA). Subcellular trafficking studies revealed that after 6 h, only 11% of the HD39/SA-PPAA conjugates had been trafficked to acidic lysosomal compartments with values at or below pH 5.6. In contrast, the average intracellular pH of HD39/SA alone dropped from 6.7 ± 0.2 at 1 h to 5.6 ± 0.5 after 3 h and 4.7 ± 0.6 after 6 h. Conjugation of the control polymer PMAA to HD39/SA showed an average pH drop similar to that of HD39/SA. Subcellular fractionation studies with tritium-labeled HD39/SA demonstrated that after 6 h, 89% of HD39/SA was associated with endosomes (Rab5+) and lysosomes (Lamp2+), while 45% of HD39/SA-PPAA was translocated to the cytosol (lactate dehydrogenase+). These results demonstrate the endosomal-releasing properties of PPAA with antibody-polymer conjugates and detail their intracellular trafficking dynamics and subcellular compartmental distributions over time.

  8. Quantitative measurement of intracellular protein dynamics using photobleaching or photoactivation of fluorescent proteins.

    PubMed

    Matsuda, Tomoki; Nagai, Takeharu

    2014-12-01

    Unlike in vitro protein dynamics, intracellular protein dynamics are intricately regulated by protein-protein interactions or interactions between proteins and other cellular components, including nucleic acids, the plasma membrane and the cytoskeleton. Alteration of these dynamics plays a crucial role in physiological phenomena such as gene expression and cell division. Live-cell imaging via microscopy with the inherent properties of fluorescent proteins, i.e. photobleaching and photoconversion, or fluorescence correlation spectroscopy, provides insight into the movement of proteins and their interactions with cellular components. This article reviews techniques based on photo-induced changes in the physicochemical properties of fluorescent proteins to measure protein dynamics inside living cells, and it also discusses the strengths and weaknesses of these techniques.

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

    PubMed Central

    Thoke, Henrik Seir; Tobiesen, Asger; Brewer, Jonathan; Hansen, Per Lyngs; Stock, Roberto P.; Olsen, Lars F.; Bagatolli, Luis A.

    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 D2O in a dose-dependent manner. These results offer a new insight into the coupling of an emergent intensive physicochemical property of the cell, i.e. cell-wide water dipolar relaxation, and a central metabolite (ATP) produced by a robustly oscillating metabolic process. PMID:25705902

  10. Fast Brillouin Optical Time Domain Analysis for dynamic sensing.

    PubMed

    Peled, Yair; Motil, Avi; Tur, Moshe

    2012-04-09

    A new technique for the fast implementation of Brillouin Optical Time Domain Analysis (BOTDA) is proposed and demonstrated, carrying the classical BOTDA method to the dynamic sensing domain. By using a digital signal generator which enables fast switching among 100 scanning frequencies, we demonstrate a truly distributed and dynamic measurement of a 100 m long fiber with a sampling rate of ~10 kHz, limited only by the fiber length and the frequency granularity. With 10 averages the standard deviation of the measured strain was ~5 µε.

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

    PubMed

    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).

  12. k-space image correlation to probe the intracellular dynamics of gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Bouzin, M.; Sironi, L.; Chirico, G.; D'Alfonso, L.; Inverso, D.; Pallavicini, P.; Collini, M.

    2016-04-01

    The collective action of dynein, kinesin and myosin molecular motors is responsible for the intracellular active transport of cargoes, vesicles and organelles along the semi-flexible oriented filaments of the cytoskeleton. The overall mobility of the cargoes upon binding and unbinding to motor proteins can be modeled as an intermittency between Brownian diffusion in the cell cytoplasm and active ballistic excursions along actin filaments or microtubules. Such an intermittent intracellular active transport, exhibited by star-shaped gold nanoparticles (GNSs, Gold Nanostars) upon internalization in HeLa cancer cells, is investigated here by combining live-cell time-lapse confocal reflectance microscopy and the spatio-temporal correlation, in the reciprocal Fourier space, of the acquired image sequences. At first, the analytical theoretical framework for the investigation of a two-state intermittent dynamics is presented for Fourier-space Image Correlation Spectroscopy (kICS). Then simulated kICS correlation functions are employed to evaluate the influence of, and sensitivity to, all the kinetic and dynamic parameters the model involves (the transition rates between the diffusive and the active transport states, the diffusion coefficient and drift velocity of the imaged particles). The optimal procedure for the analysis of the experimental data is outlined and finally exploited to derive whole-cell maps for the parameters underlying the GNSs super-diffusive dynamics. Applied here to the GNSs subcellular trafficking, the proposed kICS analysis can be adopted for the characterization of the intracellular (super-) diffusive dynamics of any fluorescent or scattering biological macromolecule.

  13. Fast Responding Voltage Regulator and Dynamic VAR Compensator

    SciTech Connect

    Divan, Deepak; Moghe, Rohit; Tholomier, Damien

    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

  14. Switching quantum dynamics for fast stabilization

    NASA Astrophysics Data System (ADS)

    Scaramuzza, Pierre; Ticozzi, Francesco

    2015-06-01

    Control strategies for dissipative preparation of target quantum states, both pure and mixed, and subspaces are obtained by switching between a set of available semigroup generators. We show that the class of problems of interest can be recast, from a control-theoretic perspective, into a switched-stabilization problem for linear dynamics. This is attained by a suitable affine transformation of the coherence-vector representation. In particular, we propose and compare stabilizing time-based and state-based switching rules for entangled state preparation, showing that the latter not only ensure faster convergence with respect to nonswitching methods, but can be designed so that they retain robustness with respect to initialization, as long as the target is a pure state or a subspace.

  15. Cycling State that Can Lead to Glassy Dynamics in Intracellular Transport

    NASA Astrophysics Data System (ADS)

    Scholz, Monika; Burov, Stanislav; Weirich, Kimberly L.; Scholz, Björn J.; Tabei, S. M. Ali; Gardel, Margaret L.; Dinner, Aaron R.

    2016-01-01

    Power-law dwell times have been observed for molecular motors in living cells, but the origins of these trapped states are not known. We introduce a minimal model of motors moving on a two-dimensional network of filaments, and simulations of its dynamics exhibit statistics comparable to those observed experimentally. Analysis of the model trajectories, as well as experimental particle tracking data, reveals a state in which motors cycle unproductively at junctions of three or more filaments. We formulate a master equation for these junction dynamics and show that the time required to escape from this vortexlike state can account for the power-law dwell times. We identify trends in the dynamics with the motor valency for further experimental validation. We demonstrate that these trends exist in individual trajectories of myosin II on an actin network. We discuss how cells could regulate intracellular transport and, in turn, biological function by controlling their cytoskeletal network structures locally.

  16. A cycling state that can lead to glassy dynamics in intracellular transport

    NASA Astrophysics Data System (ADS)

    Scholz, Monika; Burov, Stanislav; Weirich, Kimberly L.; Scholz, Bjorn J.; Tabei, S. M. Ali; Gardel, Margaret L.; Dinner, Aaron

    Power-law dwell times have been observed for molecular motors in living cells, but the origins of these trapped states are not known. We introduce a minimal model of motors moving on a two- dimensional network of filaments, and simulations of its dynamics exhibit statistics comparable to those observed experimentally. Analysis of the model trajectories, as well as experimental particle tracking data, reveals a state in which motors cycle unproductively at junctions of three or more filaments. We formulate a master equation for these junction dynamics and show that the time required to escape from this vortex-like state can account for the power-law dwell times. We identify trends in the dynamics with the motor valency for further experimental validation. We demonstrate that these trends exist in individual trajectories of myosin II on an actin network. We discuss how cells could regulate intracellular transport and, in turn, biological function, by controlling their cytoskeletal network structures locally.

  17. Automated single cell microbioreactor for monitoring intracellular dynamics and cell growth in free solution†

    PubMed Central

    Johnson-Chavarria, Eric M.; Agrawal, Utsav; Tanyeri, Melikhan; Kuhlman, Thomas E.

    2014-01-01

    We report an automated microfluidic-based platform for single cell analysis that allows for cell culture in free solution with the ability to control the cell growth environment. Using this approach, cells are confined by the sole action of gentle fluid flow, thereby enabling non-perturbative analysis of cell growth away from solid boundaries. In addition, the single cell microbioreactor allows for precise and time-dependent control over cell culture media, with the combined ability to observe the dynamics of non-adherent cells over long time scales. As a proof-of-principle demonstration, we used the platform to observe dynamic cell growth, gene expression, and intracellular diffusion of repressor proteins while precisely tuning the cell growth environment. Overall, this microfluidic approach enables the direct observation of cellular dynamics with exquisite control over environmental conditions, which will be useful for quantifying the behaviour of single cells in well-defined media. PMID:24836754

  18. Measuring near plasma membrane and global intracellular calcium dynamics in astrocytes.

    PubMed

    Shigetomi, Eiji; Khakh, Baljit S

    2009-04-26

    The brain contains glial cells. Astrocytes, a type of glial cell, have long been known to provide a passive supportive role to neurons. However, increasing evidence suggests that astrocytes may also actively participate in brain function through functional interactions with neurons. However, many fundamental aspects of astrocyte biology remain controversial, unclear and/or experimentally unexplored. One important issue is the dynamics of intracellular calcium transients in astrocytes. This is relevant because calcium is well established as an important second messenger and because it has been proposed that astrocyte calcium elevations can trigger the release of transmitters from astrocytes. However, there has not been any detailed or satisfying description of near plasma membrane calcium signaling in astrocytes. Total internal reflection fluorescence (TIRF) microscopy is a powerful tool to analyze physiologically relevant signaling events within about 100 nm of the plasma membrane of live cells. Here, we use TIRF microscopy and describe how to monitor near plasma membrane and global intracellular calcium dynamics almost simultaneously. The further refinement and systematic application of this approach has the potential to inform about the precise details of astrocyte calcium signaling. A detailed understanding of astrocyte calcium dynamics may provide a basis to understand if, how, when and why astrocytes and neurons undergo calcium-dependent functional interactions.

  19. Bat Dynamics of Female Fast Pitch Softball Batters.

    ERIC Educational Resources Information Center

    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)

  20. Quantum dynamics of fast chemical reactions

    SciTech Connect

    Light, J.C.

    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.

  1. Collisionally induced stochastic dynamics of fast ions in solids

    SciTech Connect

    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.

  2. Single-Molecule Imaging Reveals the Activation Dynamics of Intracellular Protein Smad3 on Cell Membrane

    NASA Astrophysics Data System (ADS)

    Li, Nan; Yang, Yong; He, Kangmin; Zhang, Fayun; Zhao, Libo; Zhou, Wei; Yuan, Jinghe; Liang, Wei; Fang, Xiaohong

    2016-09-01

    Smad3 is an intracellular protein that plays a key role in propagating transforming growth factor β (TGF-β) signals from cell membrane to nucleus. However whether the transient process of Smad3 activation occurs on cell membrane and how it is regulated remains elusive. Using advanced live-cell single-molecule fluorescence microscopy to image and track fluorescent protein-labeled Smad3, we observed and quantified, for the first time, the dynamics of individual Smad3 molecules docking to and activation on the cell membrane. It was found that Smad3 docked to cell membrane in both unstimulated and stimulated cells, but with different diffusion rates and dissociation kinetics. The change in its membrane docking dynamics can be used to study the activation of Smad3. Our results reveal that Smad3 binds with type I TGF-β receptor (TRI) even in unstimulated cells. Its activation is regulated by TRI phosphorylation but independent of receptor endocytosis. This study offers new information on TGF-β/Smad signaling, as well as a new approach to investigate the activation of intracellular signaling proteins for a better understanding of their functions in signal transduction.

  3. Probing cytoskeletal modulation of passive and active intracellular dynamics using nanobody-functionalized quantum dots

    PubMed Central

    Katrukha, Eugene A.; Mikhaylova, Marina; van Brakel, Hugo X.; van Bergen en Henegouwen, Paul M.; Akhmanova, Anna; Hoogenraad, Casper C.; Kapitein, Lukas C.

    2017-01-01

    The cytoplasm is a highly complex and heterogeneous medium that is structured by the cytoskeleton. How local transport depends on the heterogeneous organization and dynamics of F-actin and microtubules is poorly understood. Here we use a novel delivery and functionalization strategy to utilize quantum dots (QDs) as probes for active and passive intracellular transport. Rapid imaging of non-functionalized QDs reveals two populations with a 100-fold difference in diffusion constant, with the faster fraction increasing upon actin depolymerization. When nanobody-functionalized QDs are targeted to different kinesin motor proteins, their trajectories do not display strong actin-induced transverse displacements, as suggested previously. Only kinesin-1 displays subtle directional fluctuations, because the subset of microtubules used by this motor undergoes prominent undulations. Using actin-targeting agents reveals that F-actin suppresses most microtubule shape remodelling, rather than promoting it. These results demonstrate how the spatial heterogeneity of the cytoskeleton imposes large variations in non-equilibrium intracellular dynamics. PMID:28322225

  4. Single-Molecule Imaging Reveals the Activation Dynamics of Intracellular Protein Smad3 on Cell Membrane

    PubMed Central

    Li, Nan; Yang, Yong; He, Kangmin; Zhang, Fayun; Zhao, Libo; Zhou, Wei; Yuan, Jinghe; Liang, Wei; Fang, Xiaohong

    2016-01-01

    Smad3 is an intracellular protein that plays a key role in propagating transforming growth factor β (TGF-β) signals from cell membrane to nucleus. However whether the transient process of Smad3 activation occurs on cell membrane and how it is regulated remains elusive. Using advanced live-cell single-molecule fluorescence microscopy to image and track fluorescent protein-labeled Smad3, we observed and quantified, for the first time, the dynamics of individual Smad3 molecules docking to and activation on the cell membrane. It was found that Smad3 docked to cell membrane in both unstimulated and stimulated cells, but with different diffusion rates and dissociation kinetics. The change in its membrane docking dynamics can be used to study the activation of Smad3. Our results reveal that Smad3 binds with type I TGF-β receptor (TRI) even in unstimulated cells. Its activation is regulated by TRI phosphorylation but independent of receptor endocytosis. This study offers new information on TGF-β/Smad signaling, as well as a new approach to investigate the activation of intracellular signaling proteins for a better understanding of their functions in signal transduction. PMID:27641076

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

    SciTech Connect

    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.

  6. Nonlinear Dynamic Modeling of Neuron Action Potential Threshold During Synaptically Driven Broadband Intracellular Activity

    PubMed Central

    Roach, Shane M.; Song, Dong; Berger, Theodore W.

    2012-01-01

    Activity-dependent variation of neuronal thresholds for action potential (AP) generation is one of the key determinants of spike-train temporal-pattern transformations from presynaptic to postsynaptic spike trains. In this study, we model the nonlinear dynamics of the threshold variation during synaptically driven broadband intracellular activity. First, membrane potentials of single CA1 pyramidal cells were recorded under physiologically plausible broadband stimulation conditions. Second, a method was developed to measure AP thresholds from the continuous recordings of membrane potentials. It involves measuring the turning points of APs by analyzing the third-order derivatives of the membrane potentials. Four stimulation paradigms with different temporal patterns were applied to validate this method by comparing the measured AP turning points and the actual AP thresholds estimated with varying stimulation intensities. Results show that the AP turning points provide consistent measurement of the AP thresholds, except for a constant offset. It indicates that 1) the variation of AP turning points represents the nonlinearities of threshold dynamics; and 2) an optimization of the constant offset is required to achieve accurate spike prediction. Third, a nonlinear dynamical third-order Volterra model was built to describe the relations between the threshold dynamics and the AP activities. Results show that the model can predict threshold accurately based on the preceding APs. Finally, the dynamic threshold model was integrated into a previously developed single neuron model and resulted in a 33% improvement in spike prediction. PMID:22156947

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  9. Fast Surface Dynamics of Metallic Glass Enable Superlatticelike Nanostructure Growth

    NASA Astrophysics Data System (ADS)

    Chen, L.; Cao, C. R.; Shi, J. A.; Lu, Z.; Sun, Y. T.; Luo, P.; Gu, L.; Bai, H. Y.; Pan, M. X.; Wang, W. H.

    2017-01-01

    Contrary to the formation of complicated polycrystals induced by general crystallization, a modulated superlatticelike nanostructure, which grows layer by layer from the surface to the interior of a Pd40Ni10Cu30P20 metallic glass, is observed via isothermal annealing below the glass transition temperature. The generation of the modulated nanostructure can be solely controlled by the annealing temperature, and it can be understood based on the fast dynamic and liquidlike behavior of the glass surface. The observations have implications for understanding the glassy surface dynamics and pave a way for the controllable fabrication of a unique and sophisticated nanostructure on a glass surface to realize the properties' modification.

  10. FAST Simulation Tool Containing Methods for Predicting the Dynamic Response of Wind Turbines

    SciTech Connect

    Jonkman, Jason

    2015-08-12

    FAST is a simulation tool (computer software) for modeling tlie dynamic response of horizontal-axis wind turbines. FAST employs a combined modal and multibody structural-dynamics formulation in the time domain.

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

    NASA Astrophysics Data System (ADS)

    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.

  12. Control of Local Intracellular Calcium Concentration with Dynamic-Clamp Controlled 2-Photon Uncaging

    PubMed Central

    Idoux, Erwin; Mertz, Jerome

    2011-01-01

    The variations of the intracellular concentration of calcium ion ([Ca2+]i) are at the heart of intracellular signaling, and their imaging is therefore of enormous interest. However, passive [Ca2+]i imaging provides no control over these variations, meaning that a full exploration of the functional consequences of [Ca2+]i changes is difficult to attain. The tools designed so far to modify [Ca2+]i, even qualitatively, suffer drawbacks that undermine their widespread use. Here, we describe an electro-optical technique to quantitatively set [Ca2+]i, in real time and with sub-cellular resolution, using two-photon Ca2+ 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 [Ca2+]i variations, the functional knocking-in of user-defined virtual voltage-dependent Ca2+ channels, and the standardization of [Ca2+]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. PMID:22216105

  13. Conformational Dynamics of Intracellular Tau Protein Revealed by CD and SAXS.

    PubMed

    Gorantla, Nalini Vijay; Shkumatov, Alexander V; Chinnathambi, Subashchandrabose

    2017-01-01

    A native conformation of a protein is essential for its biological role. In certain conditions, some proteins show non-native conformations, leading to aggregation, which in turn may produce severe pathologies. Such physiological conditions are classified as protein misfolding diseases. Alzheimer's disease (AD) is the most common form of dementia. Extracellular senile plaques formed by Amyloid β and intracellular aggregates formed by microtubule-associated protein Tau (MAPT) are the hallmarks of AD. Physiological role of MAPT is to maintain the integrity and stability of microtubules, however it tends to self-aggregate forming intracellular paired helical filaments (PHFs) during AD. MAPT is also subjected to various post-translational modifications such as phosphorylation, glycosylation, truncation, and acetylation. Being natively unfolded, MAPT is prone to full characterization at atomic level. Small-angle X-ray scattering (SAXS) is often applied in combination with other biophysical methods, like nuclear magnetic resonance (NMR), circular dichroism (CD), fluorescence spectroscopy, analytical ultracentrifugation (AUC), or dynamic light scattering (DLS) to characterize natively unfolded systems. Here we describe the practical aspects of MAPT characterization by SAXS and CD in detail as well as outline the inferred structural and functional implications.

  14. Visualizing live dynamics and ultrastructure of intracellular organelles with preembedding correlative light-electron microscopy.

    PubMed

    Polishchuk, Roman S; Polishchuk, Elena V; Luini, Alberto

    2012-01-01

    One of the very effective methods to perform correlative light-electron microscopy (CLEM) is to combine video imaging of live cells with immuno-electron microscopy. This technique can thus provide detailed, high-resolution characterization of dynamic intracellular organelles. The use of green fluorescent protein (GFP)-tagged chimeras allows the movements and/or behavior of intracellular structures in a live cell to be followed, which can then be fixed at the moment of interest. The subsequent immuno-electron microscopy analysis reveals the three-dimensional (3D) architecture of the same structure, together with the precise identification of the GFP-labeled protein pattern. The process resembles taking a high-resolution snapshot of an interesting and/or rare live event. Conceptually, it consists of a switch of wavelengths, from that of photons to that of electrons, with the associated huge gain in resolution. In this respect, CLEM can be considered as the first, and probably one of the most powerful, super-resolution microscopy techniques. This switch, however, requires complex manipulations of the sample. Considering that CLEM is a very valuable but technically challenging and time-consuming method, accurate protocols are needed to simplify the efforts of researchers who are willing to apply this method for their own purposes. Here, we present a detailed description of the preembedding CLEM procedures that explains the know-how and the "tricks of the trade" that are involved in carrying out the crucial steps of CLEM.

  15. Dynamic filopodia are required for chemokine-dependent intracellular polarization during guided cell migration in vivo.

    PubMed

    Meyen, Dana; Tarbashevich, Katsiaryna; Banisch, Torsten U; Wittwer, Carolina; Reichman-Fried, Michal; Maugis, Benoît; Grimaldi, Cecilia; Messerschmidt, Esther-Maria; Raz, Erez

    2015-04-15

    Cell migration and polarization is controlled by signals in the environment. Migrating cells typically form filopodia that extend from the cell surface, but the precise function of these structures in cell polarization and guided migration is poorly understood. Using the in vivo model of zebrafish primordial germ cells for studying chemokine-directed single cell migration, we show that filopodia distribution and their dynamics are dictated by the gradient of the chemokine Cxcl12a. By specifically interfering with filopodia formation, we demonstrate for the first time that these protrusions play an important role in cell polarization by Cxcl12a, as manifested by elevation of intracellular pH and Rac1 activity at the cell front. The establishment of this polarity is at the basis of effective cell migration towards the target. Together, we show that filopodia allow the interpretation of the chemotactic gradient in vivo by directing single-cell polarization in response to the guidance cue.

  16. Slow Ca2+ dynamics in pharyngeal muscles in Caenorhabditis elegans during fast pumping.

    PubMed

    Shimozono, Satoshi; Fukano, Takashi; Kimura, Koutarou D; Mori, Ikue; Kirino, Yutaka; Miyawaki, Atsushi

    2004-05-01

    The pharyngeal muscles of Caenorhabditis elegans are composed of the corpus, isthmus and terminal bulb from anterior to posterior. These components are excited in a coordinated fashion to facilitate proper feeding through pumping and peristalsis. We analysed the spatiotemporal pattern of intracellular calcium dynamics in the pharyngeal muscles during feeding. We used a new ratiometric fluorescent calcium indicator and a new optical system that allows simultaneous illumination and detection at any two wavelengths. Pumping was observed with fast, repetitive and synchronous spikes in calcium concentrations in the corpus and terminal bulb, indicative of electrical coupling throughout the muscles. The posterior isthmus, however, responded to only one out of several pumping spikes to produce broad calcium transients, leading to peristalsis, the slow and gradual motion needed for efficient swallows. The excitation-calcium coupling may be uniquely modulated in this region at the level of calcium channels on the plasma membrane.

  17. Multiple Model-Informed Open-Loop Control of Uncertain Intracellular Signaling Dynamics

    PubMed Central

    Perley, Jeffrey P.; Mikolajczak, Judith; Harrison, Marietta L.; Buzzard, Gregery T.; Rundell, Ann E.

    2014-01-01

    Computational approaches to tune the activation of intracellular signal transduction pathways both predictably and selectively will enable researchers to explore and interrogate cell biology with unprecedented precision. Techniques to control complex nonlinear systems typically involve the application of control theory to a descriptive mathematical model. For cellular processes, however, measurement assays tend to be too time consuming for real-time feedback control and models offer rough approximations of the biological reality, thus limiting their utility when considered in isolation. We overcome these problems by combining nonlinear model predictive control with a novel adaptive weighting algorithm that blends predictions from multiple models to derive a compromise open-loop control sequence. The proposed strategy uses weight maps to inform the controller of the tendency for models to differ in their ability to accurately reproduce the system dynamics under different experimental perturbations (i.e. control inputs). These maps, which characterize the changing model likelihoods over the admissible control input space, are constructed using preexisting experimental data and used to produce a model-based open-loop control framework. In effect, the proposed method designs a sequence of control inputs that force the signaling dynamics along a predefined temporal response without measurement feedback while mitigating the effects of model uncertainty. We demonstrate this technique on the well-known Erk/MAPK signaling pathway in T cells. In silico assessment demonstrates that this approach successfully reduces target tracking error by 52% or better when compared with single model-based controllers and non-adaptive multiple model-based controllers. In vitro implementation of the proposed approach in Jurkat cells confirms a 63% reduction in tracking error when compared with the best of the single-model controllers. This study provides an experimentally

  18. Multiple model-informed open-loop control of uncertain intracellular signaling dynamics.

    PubMed

    Perley, Jeffrey P; Mikolajczak, Judith; Harrison, Marietta L; Buzzard, Gregery T; Rundell, Ann E

    2014-04-01

    Computational approaches to tune the activation of intracellular signal transduction pathways both predictably and selectively will enable researchers to explore and interrogate cell biology with unprecedented precision. Techniques to control complex nonlinear systems typically involve the application of control theory to a descriptive mathematical model. For cellular processes, however, measurement assays tend to be too time consuming for real-time feedback control and models offer rough approximations of the biological reality, thus limiting their utility when considered in isolation. We overcome these problems by combining nonlinear model predictive control with a novel adaptive weighting algorithm that blends predictions from multiple models to derive a compromise open-loop control sequence. The proposed strategy uses weight maps to inform the controller of the tendency for models to differ in their ability to accurately reproduce the system dynamics under different experimental perturbations (i.e. control inputs). These maps, which characterize the changing model likelihoods over the admissible control input space, are constructed using preexisting experimental data and used to produce a model-based open-loop control framework. In effect, the proposed method designs a sequence of control inputs that force the signaling dynamics along a predefined temporal response without measurement feedback while mitigating the effects of model uncertainty. We demonstrate this technique on the well-known Erk/MAPK signaling pathway in T cells. In silico assessment demonstrates that this approach successfully reduces target tracking error by 52% or better when compared with single model-based controllers and non-adaptive multiple model-based controllers. In vitro implementation of the proposed approach in Jurkat cells confirms a 63% reduction in tracking error when compared with the best of the single-model controllers. This study provides an experimentally

  19. Fast ion dynamics measured by collective Thomson scattering

    NASA Astrophysics Data System (ADS)

    Bindslev, Henrik

    2001-10-01

    In magnetically confined fusion plasmas, fast ions, from fusion reactions and auxiliary heating, typically carry a third of the total plasma kinetic energy, and even more of the free energy. This free energy must be channelled into heating the bulk plasma, but is also available for driving waves in the plasma, affecting confinement of bulk and fast ions. We know that fast ions can drive Alfvén waves, affect sawteeth and fishbones. In turn all three can redistribute or ejects the fast ions. Wave particle interaction, also the basis of Ion Cyclotron Resonance Heating (ICRH), depends crucially on the phase space distribution of the fast ions. Conversely the effect waves and instabilities have of fast ions will manifest itself in the detail of the fast ion phase space distribution. To explore the dynamics of fast ions and their interaction with the plasma thus begs for measurements of the fast ion distribution resolved in space, time and velocity. This has long been the promise of Collective Thomson Scattering (CTS) [1]. First demonstrated at JET [2]and subsequently at TEXTOR [3], CTS is living up to its promise and is now contributing to the understanding of fast ion dynamics. With the TEXTOR CTS, temporal behaviours of fast ion velocity distributions have been uncovered. The fast ion populations are produced by ICRH and Neutral Beam Injection (NBI). At sawteeth, we see clear variations in the fast ion population, which depend on ion energy, pitch angle and spatial location. Investigating the region just inside the inversion radius, we find that ions with small parallel energy, and with perpendicular energies up to a soft threshold well above thermal, are lost from the high field side near the inversion radius, while more energetic ions in the same pitch angle range remain insensitive to the sawteeth. The sensitive population could include the potato and stagnation orbit particles identified theoretically as being sensitive the sawteeth [4]. Under the same conditions

  20. In situ intracellular calcium oscillations in osteocytes in intact mouse long bones under dynamic mechanical loading

    PubMed Central

    Jing, Da; Baik, Andrew D.; Lu, X. Lucas; Zhou, Bin; Lai, Xiaohan; Wang, Liyun; Luo, Erping; Guo, X. Edward

    2014-01-01

    Osteocytes have been hypothesized to be the major mechanosensors in bone. How in situ osteocytes respond to mechanical stimuli is still unclear because of technical difficulties. In vitro studies have shown that osteocytes exhibited unique calcium (Ca2+) oscillations to fluid shear. However, whether this mechanotransduction phenomenon holds for in situ osteocytes embedded within a mineralized bone matrix under dynamic loading remains unknown. Using a novel synchronized loading/imaging technique, we successfully visualized in real time and quantified Ca2+ responses in osteocytes and bone surface cells in situ under controlled dynamic loading on intact mouse tibia. The resultant fluid-induced shear stress on the osteocyte in the lacunocanalicular system (LCS) was also quantified. Osteocytes, but not surface cells, displayed repetitive Ca2+ spikes in response to dynamic loading, with spike frequency and magnitude dependent on load magnitude, tissue strain, and shear stress in the LCS. The Ca2+ oscillations were significantly reduced by endoplasmic reticulum (ER) depletion and P2 purinergic receptor (P2R)/phospholipase C (PLC) inhibition. This study provides direct evidence that osteocytes respond to in situ mechanical loading by Ca2+ oscillations, which are dependent on the P2R/PLC/inositol trisphosphate/ER pathway. This study develops a novel approach in skeletal mechanobiology and also advances our fundamental knowledge of bone mechanotransduction.—Jing, D., Baik, A. D., Lu, X. L., Zhou, B., Lai, X., Wang, L., Luo, E., Guo, X. E. In situ intracellular calcium oscillations in osteocytes in intact mouse long bones under dynamic mechanical loading. PMID:24347610

  1. Fast-growing species and sustainability (productivity and site dynamics of three fast-growing species)

    SciTech Connect

    Reddy, A.N.; Sugur, G.V.

    1992-12-31

    Growth of three fast-growing species, raised in a high rainfall zone (2000-2500 mm per annum) has been compared, and the associated site dynamics studies in the Western Ghat area of Karnataka State. Two fast-growing exotics, Acacia auriculiformis and Castuarina equisitifolia, were planted on degraded, open sites at high planting densities (5000 plants ha{sup {minus}1}), and one native fast-growing species. Dendrocalamus strictus, was planted on a good site under seasonal irrigation and wider spacing (500 plants ha{sup {minus}1}). These were studies at the age of 5 years for their comparative productivity, quantity of litter fall and changes in nutrient and microbial status. Among these species, A. auriculiformis recorded the highest total productivity closely followed by D. strictus. However, the MAI after 5 years indicated a higher productivity for D. strictus, when culm production attained harvestable size. C. equisitifolia was a close third. It was also found that D. strictus produced higher biomass at lower planting densities, under better sites and management. The litter fall and changes in nutrient status indicated the highest efficiency in A. auriculiformis, followed by C. equisitifolia. It was concluded that the higher planting density was the major contributing factor; the values were comparatively low for D. strictus mainly owing to a lower stocking density of plants.

  2. Fast intracellular dissolution and persistent cellular uptake of silver nanoparticles in CHO-K1 cells: implication for cytotoxicity.

    PubMed

    Jiang, Xiumei; Miclăuş, Teodora; Wang, Liming; Foldbjerg, Rasmus; Sutherland, Duncan S; Autrup, Herman; Chen, Chunying; Beer, Christiane

    2015-03-01

    Toxicity of silver nanoparticles (Ag NPs) has been reported both in vitro and in vivo. However, the intracellular stability and chemical state of Ag NPs are still not very well studied. In this work, we systematically investigated the cellular uptake pathways, intracellular dissolution and chemical species, and cytotoxicity of Ag NPs (15.9 ± 7.6 nm) in Chinese hamster ovary cell subclone K1 cells, a cell line recommended by the OECD for genotoxicity studies. Quantification of intracellular nanoparticle uptake and ion release was performed through inductively coupled plasma mass spectrometry. X-ray absorption near-edge structure (XANES) was employed to assess the chemical state of intracellular silver. The toxic potential of Ag NPs and Ag(+) was evaluated by cell viability, reactive oxygen species (ROS) production and live-dead cell staining. The results suggest that cellular uptake of Ag NPs involves lipid-raft-mediated endocytosis and energy-independent diffusion. The degradation study shows that Ag NPs taken up into cells dissolved quickly and XANES results directly indicated that the internalized Ag was oxidized to Ag-O- species and then stabilized in silver-sulfur (Ag-S-) bonds within the cells. Subsequent cytotoxicity studies show that Ag NPs decrease cell viability and increase ROS production. Pre-incubation with N-acetyl-L-cysteine, an efficient antioxidant and Ag(+) chelator, diminished the cytotoxicity caused by Ag NPs or Ag(+) exposure. Our study suggests that the cytotoxicity mechanism of Ag NPs is related to the intracellular release of silver ions, followed by their binding to SH-groups, presumably coming from amino acids or proteins, and affecting protein functions and the antioxidant defense system of cells.

  3. Redox-responsive micelles self-assembled from dynamic covalent block copolymers for intracellular drug delivery.

    PubMed

    Yang, Qinglai; Tan, Lianjiang; He, Changyu; Liu, Bingya; Xu, Yuhong; Zhu, Zhenggang; Shao, Zhifeng; Gong, Bing; Shen, Yu-Mei

    2015-04-01

    Redox-responsive micelles self-assembled from dynamic covalent block copolymers with double disulfide linkage in the backbone have been developed successfully. The amphiphilic block copolymers PEG-PLA associated with complementary H-bonding sequences can self-assemble into spherical micelles in aqueous media with sizes from 34 nm to 107 nm with different molar mass of PEG and PLA. Moreover, in vitro drug release analyses indicate that reductive environment can result in triggered drug release profiles. The glutathione (GSH) mediated intracellular drug delivery was investigated against HeLa human cervical carcinoma cell line. Flow cytometry and fluorescence microscopy measurements demonstrated that the micelles exhibited faster drug release in glutathione monoester (GSH-OEt) pretreated HeLa cells than that in the nonpretreated cells. Cytotoxicity assay of DOX-loaded micelles indicated the higher cellular proliferation inhibition against 10 mM of GSH-OEt pretreated HeLa cells than that of the nonpretreated ones. These reduction-responsive, biodegradable and biocompatibility micelles could provide a favorable platform to construct excellent drug delivery systems for cancer therapy.

  4. Monitoring Interactions and Dynamics of Endogenous Beta-catenin With Intracellular Nanobodies in Living Cells*

    PubMed Central

    Traenkle, Bjoern; Emele, Felix; Anton, Roman; Poetz, Oliver; Haeussler, Ragna S.; Maier, Julia; Kaiser, Philipp D.; Scholz, Armin M.; Nueske, Stefan; Buchfellner, Andrea; Romer, Tina; Rothbauer, Ulrich

    2015-01-01

    β-catenin is the key component of the canonical Wnt pathway and plays a crucial role in a multitude of developmental and homeostatic processes. The different tasks of β-catenin are orchestrated by its subcellular localization and participation in multiprotein complexes. To gain a better understanding of β-catenin's role in living cells we have generated a new set of single domain antibodies, referred to as nanobodies, derived from heavy chain antibodies of camelids. We selected nanobodies recognizing the N-terminal, core or C-terminal domain of β-catenin and applied these new high-affinity binders as capture molecules in sandwich immunoassays and co-immunoprecipitations of endogenous β-catenin complexes. In addition, we engineered intracellularly functional anti-β-catenin chromobodies by combining the binding moieties of the nanobodies with fluorescent proteins. For the first time, we were able to visualize the subcellular localization and nuclear translocation of endogenous β-catenin in living cells using these chromobodies. Moreover, the chromobody signal allowed us to trace the accumulation of diffusible, hypo-phosphorylated β-catenin in response to compound treatment in real time using High Content Imaging. The anti-β-catenin nanobodies and chromobodies characterized in this study are versatile tools that enable a novel and unique approach to monitor the dynamics of subcellular β-catenin in biochemical and cell biological assays. PMID:25595278

  5. Modulation of microtubule dynamics by a TIR domain protein from the intracellular pathogen Brucella melitensis.

    PubMed

    Radhakrishnan, Girish K; Harms, Jerome S; Splitter, Gary A

    2011-10-01

    TIR (Toll/interleukin-1 receptor) domain-containing proteins play a crucial role in innate immunity in eukaryotes. Brucella is a highly infectious intracellular bacterium that encodes a TIR domain protein (TcpB) to subvert host innate immune responses to establish a beneficial niche for pathogenesis. TcpB inhibits NF-κB (nuclear factor κB) activation and pro-inflammatory cytokine secretions mediated by TLR (Toll-like receptor) 2 and TLR4. In the present study, we have demonstrated that TcpB modulates microtubule dynamics by acting as a stabilization factor. TcpB increased the rate of nucleation as well as the polymerization phases of microtubule formation in a similar manner to paclitaxel. TcpB could efficiently inhibit nocodazole- or cold-induced microtubule disassembly. Microtubule stabilization by TcpB is attributed to the BB-loop region of the TIR domain, and a point mutation affected the microtubule stabilization as well as the TLR-suppression properties of TcpB.

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

    PubMed Central

    Zylbertal, Asaph; Kahan, Anat; Ben-Shaul, Yoram; Yarom, Yosef; Wagner, Shlomo

    2015-01-01

    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. PMID:26674618

  7. Coronin1 Proteins Dictate Rac1 Intracellular Dynamics and Cytoskeletal Output

    PubMed Central

    Ojeda, Virginia; Castro-Castro, Antonio

    2014-01-01

    Rac1 regulates lamellipodium formation, myosin II-dependent contractility, and focal adhesions during cell migration. While the spatiotemporal assembly of those processes is well characterized, the signaling mechanisms involved remain obscure. We report here that the cytoskeleton-related Coronin1A and -1B proteins control a myosin II inactivation-dependent step that dictates the intracellular dynamics and cytoskeletal output of active Rac1. This step is signaling-branch specific, since it affects the functional competence of active Rac1 only when forming complexes with downstream ArhGEF7 and Pak proteins in actomyosin-rich structures. The pathway is used by default unless Rac1 is actively rerouted away from the structures by upstream activators and signals from other Rho GTPases. These results indicate that Coronin1 proteins are at the center of a regulatory hub that coordinates Rac1 activation, effector exchange, and the F-actin organization state during cell signaling. Targeting this route could be useful to hamper migration of cancer cells harboring oncogenic RAC1 mutations. PMID:24980436

  8. Dynamic filopodia are required for chemokine-dependent intracellular polarization during guided cell migration in vivo

    PubMed Central

    Meyen, Dana; Tarbashevich, Katsiaryna; Banisch, Torsten U; Wittwer, Carolina; Reichman-Fried, Michal; Maugis, Benoît; Grimaldi, Cecilia; Messerschmidt, Esther-Maria; Raz, Erez

    2015-01-01

    Cell migration and polarization is controlled by signals in the environment. Migrating cells typically form filopodia that extend from the cell surface, but the precise function of these structures in cell polarization and guided migration is poorly understood. Using the in vivo model of zebrafish primordial germ cells for studying chemokine-directed single cell migration, we show that filopodia distribution and their dynamics are dictated by the gradient of the chemokine Cxcl12a. By specifically interfering with filopodia formation, we demonstrate for the first time that these protrusions play an important role in cell polarization by Cxcl12a, as manifested by elevation of intracellular pH and Rac1 activity at the cell front. The establishment of this polarity is at the basis of effective cell migration towards the target. Together, we show that filopodia allow the interpretation of the chemotactic gradient in vivo by directing single-cell polarization in response to the guidance cue. DOI: http://dx.doi.org/10.7554/eLife.05279.001 PMID:25875301

  9. Design and mechanistic insight into ultrafast calcium indicators for monitoring intracellular calcium dynamics

    PubMed Central

    Helassa, Nordine; Podor, Borbala; Fine, Alan; Török, Katalin

    2016-01-01

    Calmodulin-based genetically encoded fluorescent calcium indicators (GCaMP-s) are powerful tools of imaging calcium dynamics from cells to freely moving animals. High affinity indicators with slow kinetics however distort the temporal profile of calcium transients. Here we report the development of reduced affinity ultrafast variants of GCaMP6s and GCaMP6f. We hypothesized that GCaMP-s have a common kinetic mechanism with a rate-limiting process in the interaction of the RS20 peptide and calcium-calmodulin. Therefore we targeted specific residues in the binding interface by rational design generating improved indicators with GCaMP6fu displaying fluorescence rise and decay times (t1/2) of 1 and 3 ms (37 °C) in vitro, 9 and 22-fold faster than GCaMP6f respectively. In HEK293T cells, GCaMP6fu revealed a 4-fold faster decay of ATP-evoked intracellular calcium transients than GCaMP6f. Stimulation of hippocampal CA1 pyramidal neurons with five action potentials fired at 100 Hz resulted in a single dendritic calcium transient with a 2-fold faster rise and 7-fold faster decay time (t1/2 of 40 ms) than GCaMP6f, indicating that tracking high frequency action potentials may be limited by calcium dynamics. We propose that the design strategy used for generating GCaMP6fu is applicable for the acceleration of the response kinetics of GCaMP-type calcium indicators. PMID:27922063

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

    PubMed Central

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

    2013-01-01

    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. PMID:23403378

  11. Fast and Slow Wetting Dynamics on nanostructured surfaces

    NASA Astrophysics Data System (ADS)

    Nandyala, Dhiraj; Rahmani, Amir; Cubaud, Thomas; Colosqui, Carlos

    2015-11-01

    This talk will present force-displacement and spontaneous drop spreading measurements on diverse nanostructured surfaces (e.g., mesoporous titania thin films, nanoscale pillared structures, on silica or glass substrates). Experimental measurements are performed for water-air and water-oil systems. The dynamics of wetting observed in these experiments can present remarkable crossovers from fast to slow or arrested dynamics. The emergence of a slow wetting regime is attributed to a multiplicity of metastable equilibrium states induced by nanoscale surface features. The crossover point can be dramatically advanced or delayed by adjusting specific physical parameters (e.g., viscosity of the wetting phases) and geometric properties of the surface nanostructure (e.g., nanopore/pillar radius and separation). Controlling the crossover point to arrested dynamics can effectively modify the degree of contact angle hysteresis and magnitude of liquid adhesion forces observed on surfaces of different materials. This work is supported by a SEED Award from The Office of Brookhaven National Laboratory Affairs at Stony Brook University.

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Dynamic Mode Decomposition of Fast Pressure Sensitive Paint Data

    PubMed Central

    Ali, Mohd Y.; Pandey, Anshuman; Gregory, James W.

    2016-01-01

    Fast-response pressure sensitive paint (PSP) is used in this work to measure and analyze the acoustic pressure field in a rectangular cavity. The high spatial resolution and fast frequency response of PSP effectively captures the spatial and temporal detail of surface pressure resulting in the acoustic pressure field. In this work, a high-speed camera is used to generate a continuous time record of the acoustic pressure fluctuations with PSP. Since the level of the acoustic pressure is near the resolution limit of the sensor system, advanced analysis techniques are used to extract the spatial modes of the pressure field. Both dynamic mode decomposition (DMD) and proper orthogonal decomposition (POD) are compared with phase averaging for data analysis. While all three techniques effectively extract the pressure field and reduce the impact of sensor noise, DMD and POD are more robust techniques that can be applied to aperiodic or multi-frequency signals. Furthermore, DMD is better than POD at suppressing noise in particular regions of the spectrum and at effectively separating spectral energy when multiple acoustic excitation frequencies are present. PMID:27294939

  14. Fast stochastic algorithm for simulating evolutionary population dynamics

    NASA Astrophysics Data System (ADS)

    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.

  15. Intracellular dynamics measurements with full field optical coherence tomography suggest hindering effect of actomyosin contractility on organelle transport

    PubMed Central

    Leroux, Charles-Edouard; Bertillot, Fabien; Thouvenin, Olivier; Boccara, Albert-Claude

    2016-01-01

    Intracellular motion can be quantitatively monitored in tissues using coherence-gated microscopic techniques. With full-field optical coherence tomography (FFOCT), the use of high numerical aperture microscope objectives provides a high resolution mapping of intracellular dynamics that are probed with subwavelength sensitivity. In the upper temporal bandwidth that we have used (1-6 Hz) the main contribution to the dynamic signal arises from the overall dynamical, optically heterogeneous cytoplasm. We propose a method to specifically study the impact of actomyosin contractility on the intracellular dynamic signal by performing high throughput, comparative measurements of multicellular aggregates with and without blebbistatin action, a selective inhibitor of class-II myosins that disrupts actomyosin contractile activity. Our results indicate a significant increase in the fraction of the signal that decorrelates within 1 second after inhibition of contractility. This observation mitigates the anticipated importance of actomyosin contractile forces to directly move organelles, but highlights their role in hindering organelle transport via their stiffening effect of the viscoelastic cytoplasm. PMID:27895991

  16. Wind turbine control systems: Dynamic model development using system identification and the fast structural dynamics code

    SciTech Connect

    Stuart, J.G.; Wright, A.D.; Butterfield, C.P.

    1996-10-01

    Mitigating the effects of damaging wind turbine loads and responses extends the lifetime of the turbine and, consequently, reduces the associated Cost of Energy (COE). Active control of aerodynamic devices is one option for achieving wind turbine load mitigation. Generally speaking, control system design and analysis requires a reasonable dynamic model of {open_quotes}plant,{close_quotes} (i.e., the system being controlled). This paper extends the wind turbine aileron control research, previously conducted at the National Wind Technology Center (NWTC), by presenting a more detailed development of the wind turbine dynamic model. In prior research, active aileron control designs were implemented in an existing wind turbine structural dynamics code, FAST (Fatigue, Aerodynamics, Structures, and Turbulence). In this paper, the FAST code is used, in conjunction with system identification, to generate a wind turbine dynamic model for use in active aileron control system design. The FAST code is described and an overview of the system identification technique is presented. An aileron control case study is used to demonstrate this modeling technique. The results of the case study are then used to propose ideas for generalizing this technique for creating dynamic models for other wind turbine control applications.

  17. Dynamic intracellular delivery of antibiotics via pH-responsive polymersomes.

    PubMed

    Lane, D D; Su, F Y; Chiu, D Y; Srinivasan, S; Wilson, J T; Ratner, D M; Stayton, P S; Convertine, A J

    2015-02-28

    Reversible addition-fragmentation chain transfer (RAFT) polymerization was employed to prepare a series of copolymers consisting of 2-hdroxyethyl methacrylate (HEMA) and poly(ethylene glycol) methyl ether methacrylate (FWavg ~ 950 Da) (O950) with variable comonomer compositions and molecular weights for use as polymeric scaffolds. Reactivity ratios for the monomer pair were determined to be 1.37 and 0.290 respectively. To these scaffolds trithiocarbonate-based RAFT chain transfer agents (CTAs) were grafted using carbodiimide chemistry. The resultant graft chain transfer agents (gCTA) were subsequently employed to polymerize dimethylaminoethyl methacrylate (DMAEMA) and (HPMA) between degrees of polymerization (DP) of 25 and 200. Kinetic analysis for the polymerization of DMAEMA targeting a DP of 100 from a 34 arm graft gCTA show linear Mn conversion and pseudo first order rate plots with narrow molecular weight distributions that move toward lower elution volumes with monomer conversion. Đ values for these polymerizations remain low at around 1.20 at monomer conversions as high as 70 %. pH-responsive endosomalytic brushes capable of spontaneously self-assembling into polymersomes were synthesized and a combination of dynamic light scattering (DLS), cryoTEM, and red blood cell hemolysis were employed to evaluate the aqueous solution properties of the polymeric brush as a function of pH. Successful encapsulation of ceftazidime and pH-dependent drug release properties were confirmed by HPLC. Intracellular antibiotic activity of the drug-loaded polymersomes was confirmed in a macrophage coculture model of infection with B. thailandensis and RAW 264.7 cells.

  18. Dynamic intracellular delivery of antibiotics via pH-responsive polymersomes

    PubMed Central

    Lane, D.D.; Su, F.Y.; Chiu, D.Y.; Srinivasan, S.; Wilson, J.T.; Ratner, D.M.; Stayton, P.S.; Convertine, A.J.

    2014-01-01

    Reversible addition-fragmentation chain transfer (RAFT) polymerization was employed to prepare a series of copolymers consisting of 2-hdroxyethyl methacrylate (HEMA) and poly(ethylene glycol) methyl ether methacrylate (FWavg ~ 950 Da) (O950) with variable comonomer compositions and molecular weights for use as polymeric scaffolds. Reactivity ratios for the monomer pair were determined to be 1.37 and 0.290 respectively. To these scaffolds trithiocarbonate-based RAFT chain transfer agents (CTAs) were grafted using carbodiimide chemistry. The resultant graft chain transfer agents (gCTA) were subsequently employed to polymerize dimethylaminoethyl methacrylate (DMAEMA) and (HPMA) between degrees of polymerization (DP) of 25 and 200. Kinetic analysis for the polymerization of DMAEMA targeting a DP of 100 from a 34 arm graft gCTA show linear Mn conversion and pseudo first order rate plots with narrow molecular weight distributions that move toward lower elution volumes with monomer conversion. Đ values for these polymerizations remain low at around 1.20 at monomer conversions as high as 70 %. pH-responsive endosomalytic brushes capable of spontaneously self-assembling into polymersomes were synthesized and a combination of dynamic light scattering (DLS), cryoTEM, and red blood cell hemolysis were employed to evaluate the aqueous solution properties of the polymeric brush as a function of pH. Successful encapsulation of ceftazidime and pH-dependent drug release properties were confirmed by HPLC. Intracellular antibiotic activity of the drug-loaded polymersomes was confirmed in a macrophage coculture model of infection with B. thailandensis and RAW 264.7 cells. PMID:26097513

  19. Dynamics of Inorganic Nutrients in Intertidal Sediments: Porewater, Exchangeable, and Intracellular Pools.

    PubMed

    Garcia-Robledo, Emilio; Bohorquez, Julio; Corzo, Alfonso; Jimenez-Arias, Juan L; Papaspyrou, Sokratis

    2016-01-01

    The study of inorganic nutrients dynamics in shallow sediments usually focuses on two main pools: porewater (PW) nutrients and 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 alternative nitrate

  20. Dynamics of Inorganic Nutrients in Intertidal Sediments: Porewater, Exchangeable, and Intracellular Pools

    PubMed Central

    Garcia-Robledo, Emilio; Bohorquez, Julio; Corzo, Alfonso; Jimenez-Arias, Juan L.; Papaspyrou, Sokratis

    2016-01-01

    The study of inorganic nutrients dynamics in shallow sediments usually focuses on two main pools: porewater (PW) nutrients and 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 alternative nitrate

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Intracellular Phosphate Dynamics in Muscle Measured by Magnetic Resonance Spectroscopy during Hemodialysis.

    PubMed

    Lemoine, Sandrine; Fournier, Thomas; Kocevar, Gabriel; Belloi, Amélie; Normand, Gabrielle; Ibarrola, Danielle; Sappey-Marinier, Dominique; Juillard, Laurent

    2016-07-01

    Of the 600-700 mg inorganic phosphate (Pi) removed during a 4-hour hemodialysis session, a maximum of 10% may be extracted from the extracellular space. The origin of the other 90% of removed phosphate is unknown. This study tested the hypothesis that the main source of phosphate removed during hemodialysis is the intracellular compartment. Six binephrectomized pigs each underwent one 3-hour hemodialysis session, during which the extracorporeal circulation blood flow was maintained between 100 and 150 ml/min. To determine in vivo phosphate metabolism, we performed phosphorous ((31)P) magnetic resonance spectroscopy using a 1.5-Tesla system and a surface coil placed over the gluteal muscle region. (31)P magnetic resonance spectra (repetition time =10 s; echo time =0.35 ms) were acquired every 160 seconds before, during, and after dialysis. During the dialysis sessions, plasma phosphate concentrations decreased rapidly (-30.4 %; P=0.003) and then, plateaued before increasing approximately 30 minutes before the end of the sessions; 16 mmol phosphate was removed in each session. When extracellular phosphate levels plateaued, intracellular Pi content increased significantly (11%; P<0.001). Moreover, βATP decreased significantly (P<0.001); however, calcium levels remained balanced. Results of this study show that intracellular Pi is the source of Pi removed during dialysis. The intracellular Pi increase may reflect cellular stress induced by hemodialysis and/or strong intracellular phosphate regulation.

  3. CaMKII regulates intracellular Ca²⁺ dynamics in native endothelial cells.

    PubMed

    Toussaint, Fanny; Charbel, Chimène; Blanchette, Alexandre; Ledoux, Jonathan

    2015-09-01

    Localized endothelial Ca(2+) signalling, such as Ca(2+) pulsars, can modulate the contractile state of the underlying vascular smooth muscle cell through specific endothelial targets. In addition to K(Ca)3.1 as a target, Ca(2+) pulsars, an IP3R-dependent pulsatile Ca(2+) release from the endoplasmic reticulum (ER) could activate a frequency-sensitive Ca(2+)-dependent kinase such as CaMKII. In the absence of extracellular Ca(2+), acetylcholine increased endothelial CaMKII phosphorylation and activation, thereby suggesting CaMKII activation independently of Ca(2+) influx. Herein, a reciprocal relation where CaMKII controls endothelial Ca(2+) dynamics has been investigated in mesenteric arteries. Both CaMKIIα and β isoforms have been identified in endothelial cells and close proximity (<40 nm) suggests their association in heteromultimers. Intracellular Ca(2+) monitoring with high speed confocal microscopy then showed that inhibition of CaMKII with KN-93 significantly increased the population of Ca(2+) pulsars active sites (+89%), suggesting CaMKII as a major regulator of Ca(2+) pulsars in native endothelium. Mechanistic insights were then sought through the elucidation of the impact of CaMKII on ER Ca(2+) store. ER Ca(2+) emptying was accelerated by CaMKII inhibition and ER Ca(2+) content was assessed using ionomycin. Exposure to KN-93 strongly diminished ER Ca(2+) content (-61%) by relieving CaMKII-dependent inhibition of IP3 receptors (IP3R). Moreover, in situ proximity ligation assay suggested CaMKII-IP3R promiscuity, essential condition for a protein-protein interaction. Interestingly, segregation of IP3R within myoendothelial projection (MEP) appears to be isoform-specific. Hence, only IP3R type 1 and type 2 are detected within fenestrations of the internal elastic lamina, sites of MEP, whilst type 3 is absent from these structures. In summary, CaMKII seems to act as a Ca(2+)-sensitive switch of a negative feedback loop regulating endothelial Ca(2

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

    NASA Astrophysics Data System (ADS)

    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.

  5. Fast method for dynamic thresholding in volume holographic memories

    NASA Astrophysics Data System (ADS)

    Porter, Michael S.; Mitkas, Pericles A.

    1998-11-01

    It is essential for parallel optical memory interfaces to incorporate processing that dynamically differentiates between databit values. These thresholding points will vary as a result of system noise -- due to contrast fluctuations, variations in data page composition, reference beam misalignment, etc. To maintain reasonable data integrity it is necessary to select the threshold close to its optimal level. In this paper, a neural network (NN) approach is proposed as a fast method of determining the threshold to meet the required transfer rate. The multi-layered perceptron network can be incorporated as part of a smart photodetector array (SPA). Other methods have suggested performing the operation by means of histogram or by use of statistical information. These approaches fail in that they unnecessarily switch to a 1-D paradigm. In this serial domain, global thresholding is pointless since sequence detection could be applied. The discussed approach is a parallel solution with less overhead than multi-rail encoding. As part of this method, a small set of values are designated as threshold determination data bits; these are interleaved with the information data bits and are used as inputs to the NN. The approach has been tested using both simulated data as well as data obtained from a volume holographic memory system. Results show convergence of the training and an ability to generalize upon untrained data for binary and multi-level gray scale datapage images. Methodologies are discussed for improving the performance by a proper training set selection.

  6. Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent Notch signaling.

    PubMed

    Paul, Manash K; Bisht, Bharti; Darmawan, Daphne O; Chiou, Richard; Ha, Vi L; Wallace, William D; Chon, Andrew T; Hegab, Ahmed E; Grogan, Tristan; Elashoff, David A; Alva-Ornelas, Jackelyn A; Gomperts, Brigitte N

    2014-08-07

    Airways are exposed to myriad environmental and damaging agents such as reactive oxygen species (ROS), which also have physiological roles as signaling molecules that regulate stem cell function. However, the functional significance of both steady and dynamically changing ROS levels in different stem cell populations, as well as downstream mechanisms that integrate ROS sensing into decisions regarding stem cell homeostasis, are unclear. Here, we show in mouse and human airway basal stem cells (ABSCs) that intracellular flux from low to moderate ROS levels is required for stem cell self-renewal and proliferation. Changing ROS levels activate Nrf2, which activates the Notch pathway to stimulate ABSC self-renewal and an antioxidant program that scavenges intracellular ROS, returning overall ROS levels to a low state to maintain homeostatic balance. This redox-mediated regulation of lung stem cell function has significant implications for stem cell biology, repair of lung injuries, and diseases such as cancer.

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

    PubMed

    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.

  8. [Dynamic variance of intracellular metabolic energies under rhythmical control for dissolved oxygen in PHB mixed cultivation].

    PubMed

    Qian, Z W; Tohyama, M; Hua, Q; Shimizu, K

    2001-07-01

    The mixed cultivation using cheaper carbon source-wasted food material contained glucose and lactate at the same time was conducted in 5L fermentor, within which glucose was converted to lactate by L. delbrueckii in anaerobic condition and the lactate was converted to PHB by R. eutropha in aerobic condition. Considering dissolved oxygen concentration may affect the level of intracellular ATP and NADPH of the metabolic pathways for R. eutropha in lactate under autotrophy or heterotrophy, rhythmical oscillated control for DO based on chaos control method was consequently presented. This method was employed to satisfy two strains for opposite oxygen preferences, moreover, excite the intracellular metabolic energy simultaneously. The values examined through spectrophotofluorimetry represented that both ATP and NADPH exhibited fluctuations in accordance with the DO rhythm. By means of this control design, the concentration of PHB can be doubled than the usual under stable DO control.

  9. NMR Dynamics of Transmembrane and Intracellular Domains of p75NTR in Lipid-Protein Nanodiscs

    PubMed Central

    Mineev, Konstantin S.; Goncharuk, Sergey A.; Kuzmichev, Pavel K.; Vilar, Marçal; Arseniev, Alexander S.

    2015-01-01

    P75NTR is a type I integral membrane protein that plays a key role in neurotrophin signaling. However, structural data for the receptor in various functional states are sparse and controversial. In this work, we studied the spatial structure and mobility of the transmembrane and intracellular parts of p75NTR, incorporated into lipid-protein nanodiscs of various sizes and compositions, by solution NMR spectroscopy. Our data reveal a high level of flexibility and disorder in the juxtamembrane chopper domain of p75NTR, which results in the motions of the receptor death domain being uncoupled from the motions of the transmembrane helix. Moreover, none of the intracellular domains of p75NTR demonstrated a propensity to interact with the membrane or to self-associate under the experimental conditions. The obtained data are discussed in the context of the receptor activation mechanism. PMID:26287629

  10. A simulation and estimation framework for intracellular dynamics and trafficking in video-microscopy and fluorescence imagery.

    PubMed

    Boulanger, Jérôme; Kervrann, Charles; Bouthemy, Patrick

    2009-02-01

    Image sequence analysis in video-microscopy has now gained importance since molecular biology is presently having a profound impact on the way research is being conducted in medicine. However, image processing techniques that are currently used for modeling intracellular dynamics, are still relatively crude and yield imprecise results. Indeed, complex interactions between a large number of small moving particles in a complex scene cannot be easily modeled, limiting the performance of object detection and tracking algorithms. This motivates our present research effort which is to develop a general estimation/simulation framework able to produce image sequences showing small moving spots in interaction, with variable velocities, and corresponding to intracellular dynamics and trafficking in biology. It is now well established that spot/object trajectories can play a role in the analysis of living cell dynamics and simulating realistic image sequences is then of major importance. We demonstrate the potential of the proposed simulation/estimation framework in experiments, and show that this approach can also be used to evaluate the performance of object detection/tracking algorithms in video-microscopy and fluorescence imagery.

  11. Confinement and dynamics of neutral beam injected fast ions in the MST Reversed Field Pinch

    NASA Astrophysics Data System (ADS)

    Liu, D.; Almagri, F.; Anderson, J. K.; den Hartog, D. J.; Nornberg, M. D.; Sarff, J. S.; Waksman, J.; Fiksel, G.; Deichuli, P.; Davydenko, V. I.; Ivanov, A. A.; Polosatkin, S. V.; Stupishin, N.; Andre, R.; McCune, D.

    2010-11-01

    The new 1MW neutral beam injector (97% H, 3% D) on MST provides a good test-bed for study of fast ions in the RFP. Analysis of the D-D fusion neutron flux decay at beam turn-off reveals that the confinement time of the fast ions is at least 10 ms, ten-fold larger than the thermal conferment times for particles and energy in standard stochastic plasmas. Also, the fast ion confinement increases with magnetic field strength. Dependence of fast ion confinement on plasma parameters, beam energy, and injection direction will be characterized and compared with TRANSP simulations. In addition, an advanced neutral particle analyzer and a prototype of fast ion charge exchange spectroscopy are under construction to measure neutralized fast ions and induced Doppler-shifted Hα light, respectively, thereby resolving fast ion density and energy distribution. Initial measurements of fast-ion dynamics during magnetic reconnection events will be presented.

  12. Intracellular calcium dynamics permit a Purkinje neuron model to perform toggle and gain computations upon its inputs.

    PubMed

    Forrest, Michael D

    2014-01-01

    Without synaptic input, Purkinje neurons can spontaneously fire in a repeating trimodal pattern that consists of tonic spiking, bursting and quiescence. Climbing fiber input (CF) switches Purkinje neurons out of the trimodal firing pattern and toggles them between a tonic firing and a quiescent state, while setting the gain of their response to Parallel Fiber (PF) input. The basis to this transition is unclear. We investigate it using a biophysical Purkinje cell model under conditions of CF and PF input. The model can replicate these toggle and gain functions, dependent upon a novel account of intracellular calcium dynamics that we hypothesize to be applicable in real Purkinje cells.

  13. A dynamically changing intracellular water network serves as a universal regulator of the cell: the water-governed cycle.

    PubMed

    Szolnoki, Zoltán

    2007-06-01

    The functioning of enzymes and protein folding are well known to be assisted by the surrounding chaperoning water molecules, which are connected to the protein via non-covalent, dynamically changing chemical bonds. A molecular intracellular network of weak non-covalent connections may be presumed to exist in living cells. The roles of such non-covalent networks are examined in terms of a molecular model which postulates a universal enzyme and biochemical mechanism regulating the maintenance of chemical stability in living cells.

  14. Implications of receptor-mediated endocytosis and intracellular trafficking dynamics in the development of antibody drug conjugates

    PubMed Central

    Ritchie, Michael; Tchistiakova, Lioudmila; Scott, Nathan

    2013-01-01

    The use of antibody-drug conjugates (ADCs) as a therapeutic platform to treat cancer has recently gained substantial momentum. This therapeutic modality has the potential to increase the efficacy and reduce the systemic toxicity associated with current therapeutic regimens. The efficacy of ADCs, however, relies on the proper exploitation of intracellular sorting dynamics of the antigen as well as the specificity, selectivity and pharmacokinetic properties of the antibody itself. Our understanding of endocytosis and endosomal trafficking of receptors has appreciably increased in recent years, as improvements in the assays used to study these events have resolved many of the molecular mechanisms regulating these processes. As a result, we now have the knowledge necessary to exploit these pathways efficiently to improve the efficacy of antibody-based therapy. This review discusses some recent studies that have explored how endo/lysosomal dynamics can affect the efficacy of engineered therapeutic antibodies, including ADCs. PMID:23221464

  15. Sound-Induced Intracellular Ca2+ Dynamics in the Adult Hearing Cochlea

    PubMed Central

    Chan, Dylan K.; Rouse, Stephanie L.

    2016-01-01

    Ca2+ signaling has been implicated in the initial pathophysiologic mechanisms underlying the cochlea's response to acoustic overstimulation. Intracellular Ca2+ signaling (ICS) waves, which occur in glia and retinal cells in response to injury to activate cell regulatory pathways, have been proposed as an early event in cochlear injury. Disruption of ICS activity is thought to underlie Connexin 26-associated hearing loss, the most common genetic form of deafness, and downstream sequelae of ICS wave activity, such as MAP kinase pathway activation, have been implicated in noise-induced hearing loss. However, ICS waves have only been observed in neonatal cochlear cultures and are thought to be quiescent after the onset of hearing. In this study, we employ an acute explant model of an adult, hearing cochlea that retains many in vivo physiologic features to investigate Ca2+ changes in response to sound. We find that both slow monotonic changes in intracellular Ca2+ concentration as well as discrete ICS waves occur with acoustic overstimulation. The ICS waves share many intrinsic features with their better-described neonatal counterparts, including ATP and gap-junction dependence, and propagation velocity and distance. This identification of ICS wave activity in the adult, hearing cochlea thus confirms and characterizes an important early detection mechanism for cochlear trauma and provides a target for interventions for noise-induced and Connexin 26-associated hearing loss. PMID:27959894

  16. Chondrocyte intracellular calcium, cytoskeletal organization, and gene expression responses to dynamic osmotic loading.

    PubMed

    Chao, Pen-Hsiu Grace; West, Alan C; Hung, Clark T

    2006-10-01

    While chondrocytes in articular cartilage experience dynamic stimuli from joint loading activities, few studies have examined the effects of dynamic osmotic loading on their signaling and biosynthetic activities. We hypothesize that dynamic osmotic loading modulates chondrocyte signaling and gene expression differently than static osmotic loading. With the use of a novel microfluidic device developed in our laboratory, dynamic hypotonic loading (-200 mosM) was applied up to 0.1 Hz and chondrocyte calcium signaling, cytoskeleton organization, and gene expression responses were examined. Chondrocytes exhibited decreasing volume and calcium responses with increasing loading frequency. Phalloidin staining showed osmotic loading-induced changes to the actin cytoskeleton in chondrocytes. Real-time PCR analysis revealed a stimulatory effect of dynamic osmotic loading compared with static osmotic loading. These studies illustrate the utility of the microfluidic device in cell signaling investigations, and their potential role in helping to elucidate mechanisms that mediate chondrocyte mechanotransduction to dynamic stimuli.

  17. A Novel Optical Intracellular Imaging Approach for Potassium Dynamics in Astrocytes

    PubMed Central

    Rimmele, Theresa S.; Chatton, Jean-Yves

    2014-01-01

    Astrocytes fulfill a central role in regulating K+ and glutamate, both released by neurons into the extracellular space during activity. Glial glutamate uptake is a secondary active process that involves the influx of three Na+ ions and one proton and the efflux of one K+ ion. Thus, intracellular K+ concentration ([K+]i) is potentially influenced both by extracellular K+ concentration ([K+]o) fluctuations and glutamate transport in astrocytes. We evaluated the impact of these K+ ion movements on [K+]i in primary mouse astrocytes by microspectrofluorimetry. We established a new noninvasive and reliable approach to monitor and quantify [K+]i using the recently developed K+ sensitive fluorescent indicator Asante Potassium Green-1 (APG-1). An in situ calibration procedure enabled us to estimate the resting [K+]i at 133±1 mM. We first investigated the dependency of [K+]i levels on [K+]o. We found that [K+]i followed [K+]o changes nearly proportionally in the range 3–10 mM, which is consistent with previously reported microelectrode measurements of intracellular K+ concentration changes in astrocytes. We then found that glutamate superfusion caused a reversible drop of [K+]i that depended on the glutamate concentration with an apparent EC50 of 11.1±1.4 µM, corresponding to the affinity of astrocyte glutamate transporters. The amplitude of the [K+]i drop was found to be 2.3±0.1 mM for 200 µM glutamate applications. Overall, this study shows that the fluorescent K+ indicator APG-1 is a powerful new tool for addressing important questions regarding fine [K+]i regulation with excellent spatial resolution. PMID:25275375

  18. A novel optical intracellular imaging approach for potassium dynamics in astrocytes.

    PubMed

    Rimmele, Theresa S; Chatton, Jean-Yves

    2014-01-01

    Astrocytes fulfill a central role in regulating K+ and glutamate, both released by neurons into the extracellular space during activity. Glial glutamate uptake is a secondary active process that involves the influx of three Na+ ions and one proton and the efflux of one K+ ion. Thus, intracellular K+ concentration ([K+]i) is potentially influenced both by extracellular K+ concentration ([K+]o) fluctuations and glutamate transport in astrocytes. We evaluated the impact of these K+ ion movements on [K+]i in primary mouse astrocytes by microspectrofluorimetry. We established a new noninvasive and reliable approach to monitor and quantify [K+]i using the recently developed K+ sensitive fluorescent indicator Asante Potassium Green-1 (APG-1). An in situ calibration procedure enabled us to estimate the resting [K+]i at 133±1 mM. We first investigated the dependency of [K+]i levels on [K+]o. We found that [K+]i followed [K+]o changes nearly proportionally in the range 3-10 mM, which is consistent with previously reported microelectrode measurements of intracellular K+ concentration changes in astrocytes. We then found that glutamate superfusion caused a reversible drop of [K+]i that depended on the glutamate concentration with an apparent EC50 of 11.1±1.4 µM, corresponding to the affinity of astrocyte glutamate transporters. The amplitude of the [K+]i drop was found to be 2.3±0.1 mM for 200 µM glutamate applications. Overall, this study shows that the fluorescent K+ indicator APG-1 is a powerful new tool for addressing important questions regarding fine [K+]i regulation with excellent spatial resolution.

  19. Using dynamic interferometric synthetic aperature radar (InSAR) to image fast-moving surface waves

    DOEpatents

    Vincent, Paul

    2005-06-28

    A new differential technique and system for imaging dynamic (fast moving) surface waves using Dynamic Interferometric Synthetic Aperture Radar (InSAR) is introduced. This differential technique and system can sample the fast-moving surface displacement waves from a plurality of moving platform positions in either a repeat-pass single-antenna or a single-pass mode having a single-antenna dual-phase receiver or having dual physically separate antennas, and reconstruct a plurality of phase differentials from a plurality of platform positions to produce a series of desired interferometric images of the fast moving waves.

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

    PubMed

    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.

  1. Relationship between L-glutamate-regulated intracellular Na+ dynamics and ATP hydrolysis in astrocytes.

    PubMed

    Magistretti, P J; Chatton, J-Y

    2005-01-01

    Glutamate uptake into astrocytes and the resulting increase in intracellular Na+ (Na+(i)) have been identified as a key signal coupling excitatory neuronal activity to increased glucose utilization. Arguments based mostly on mathematical modeling led to the conclusion that physiological concentrations of glutamate more than double astrocytic Na+/K+-ATPase activity, which should proportionally increase its ATP hydrolysis rate. This hypothesis was tested in the present study by fluorescence monitoring of free Mg2+ (Mg2+(i)), a parameter that inversely correlates with ATP levels. Glutamate application measurably increased Mg2+(i) (i.e. decreased ATP), which was reversible after glutamate washout. Na+(i) and ATP changes were then directly compared by simultaneous Na+(i) and Mg2+ imaging. Glutamate increased both parameters with different rates and blocking the Na+/K+-ATPase during the glutamate-evoked Na+(i) response, resulted in a drop of Mg2+(i) levels (i.e. increased ATP). Taken together, this study demonstrates the tight correlation between glutamate transport, Na+ homeostasis and ATP levels in astrocytes.

  2. Dynamics of reductive genome evolution in mitochondria and obligate intracellular microbes.

    PubMed

    Khachane, Amit N; Timmis, Kenneth N; Martins dos Santos, Vítor A P

    2007-02-01

    Reductive evolution in mitochondria and obligate intracellular microbes has led to a significant reduction in their genome size and guanine plus cytosine content (GC). We show that genome shrinkage during reductive evolution in prokaryotes follows an exponential decay pattern and provide a method to predict the extent of this decay on an evolutionary timescale. We validated predictions by comparison with estimated extents of genome reduction known to have occurred in mitochondria and Buchnera aphidicola, through comparative genomics and by drawing on available fossil evidences. The model shows how the mitochondrial ancestor would have quickly shed most of its genome, shortly after its incorporation into the protoeukaryotic cell and prior to codivergence subsequent to the split of eukaryotic lineages. It also predicts that the primary rickettsial parasitic event would have occurred between 180 and 425 million years ago (MYA), an event of relatively recent evolutionary origin considering the fact that Rickettsia and mitochondria evolved from a common alphaproteobacterial ancestor. This suggests that the symbiotic events of Rickettsia and mitochondria originated at different time points. Moreover, our model results predict that the ancestor of Wigglesworthia glossinidia brevipalpis, dated around the time of origin of its symbiotic association with the tsetse fly (50-100 MYA), was likely to have been an endosymbiont itself, thus supporting an earlier proposition that Wigglesworthia, which is currently a maternally inherited primary endosymbiont, evolved from a secondary endosymbiont.

  3. A Bidirectional System for the Dynamic Small Molecule Control of Intracellular Fusion Proteins

    PubMed Central

    Kuzin, Alexander P.; Lew, Scott; Seetharaman, Jayaraman; Acton, Thomas B.; Kornhaber, Gregory J.; Xiao, Rong; Montelione, Gaetano Thomas; Tong, Liang; Crews, Craig M.

    2014-01-01

    Small molecule control of intracellular protein levels allows temporal and dose-dependent regulation of protein function. Recently, we developed a method to degrade proteins fused to a mutant dehalogenase (HaloTag2) using small molecule hydrophobic tags (HyTs). Here, we introduce a complementary method to stabilize the same HaloTag2 fusion proteins, resulting in a unified system allowing bidirectional control of cellular protein levels in a temporal and dose-dependent manner. From a small molecule screen, we identified N-(3,5-dichloro-2-ethoxybenzyl)-2H-tetrazol-5-amine as a nanomolar HALoTag2 Stabilizer (HALTS1) that reduces the Hsp70:HaloTag2 interaction, thereby preventing HaloTag2 ubiquitination. Finally, we demonstrate the utility of the HyT/HALTS system in probing the physiological role of therapeutic targets by modulating HaloTag2-fused oncogenic H-Ras, which resulted in either the cessation (HyT) or acceleration (HALTS) of cellular transformation. In sum, we present a general platform to study protein function, whereby any protein of interest fused to HaloTag2 can be either degraded 10-fold or stabilized 5-fold using two corresponding compounds. PMID:23978068

  4. A bidirectional system for the dynamic small molecule control of intracellular fusion proteins.

    PubMed

    Neklesa, Taavi K; Noblin, Devin J; Kuzin, Alexander; Lew, Scott; Seetharaman, Jayaraman; Acton, Thomas B; Kornhaber, Gregory; Xiao, Rong; Montelione, Gaetano T; Tong, Liang; Crews, Craig M

    2013-10-18

    Small molecule control of intracellular protein levels allows temporal and dose-dependent regulation of protein function. Recently, we developed a method to degrade proteins fused to a mutant dehalogenase (HaloTag2) using small molecule hydrophobic tags (HyTs). Here, we introduce a complementary method to stabilize the same HaloTag2 fusion proteins, resulting in a unified system allowing bidirectional control of cellular protein levels in a temporal and dose-dependent manner. From a small molecule screen, we identified N-(3,5-dichloro-2-ethoxybenzyl)-2H-tetrazol-5-amine as a nanomolar HALoTag2 Stabilizer (HALTS1) that reduces the Hsp70:HaloTag2 interaction, thereby preventing HaloTag2 ubiquitination. Finally, we demonstrate the utility of the HyT/HALTS system in probing the physiological role of therapeutic targets by modulating HaloTag2-fused oncogenic H-Ras, which resulted in either the cessation (HyT) or acceleration (HALTS) of cellular transformation. In sum, we present a general platform to study protein function, whereby any protein of interest fused to HaloTag2 can be either degraded 10-fold or stabilized 5-fold using two corresponding compounds.

  5. Tunable PIE and synchronized gating detections by FastFLIM for quantitative microscopy measurements of fast dynamics of single molecules

    NASA Astrophysics Data System (ADS)

    Sun, Yuansheng; Coskun, Ulas; Ferreon, Allan Chris; Barbieri, Beniamino; Liao, Shih-Chu Jeff

    2016-03-01

    The crosstalk between two fluorescent species causes problems in fluorescence microscopy imaging, especially for quantitative measurements such as co-localization, Förster resonance energy transfer (FRET), fluorescence cross correlation spectroscopy (FCCS). In laser scanning confocal microscopy, the lasers can be switched on and off by acousto-optic tunable filters (AOTF) in the microsecond scale for alternative line scanning in order to avoid the crosstalk while minimizing the time delay between two lasers on the same pixel location. In contrast, the pulsed interleaved excitation (PIE) technique synchronizes two pulsed lasers of different wavelengths in the nanosecond scale to enable measuring superfast dynamics of two fluorescent species simultaneously and yet quantitatively without the crosstalk contamination. This feature is critical for many cell biology applications, e.g. accurate determination of stoichiometry in FRET measurements for studying protein-protein interactions or cell signal events, detection of weaker bindings in FCCS by eliminating the false cross correlation due to the crosstalk. The PIE has been used with the time correlated single photon counting (TCSPC) electronics. Here, we describe a novel PIE development using the digital frequency domain (DFD) technique -- FastFLIM, which provides tunable PIE setups and synchronized gating detections, tailored and optimized to specific applications. A few PIE setups by FastFLIM and measurement examples are described. Combined with the sensitivity of Alba and Q2 systems, the PIE allowed us to quantitatively measure the fast dynamics of single molecules.

  6. Extremely Fast Numerical Integration of Ocean Surface Wave Dynamics

    DTIC Science & Technology

    2007-09-30

    1) is a natural two-space-dimension extension of the KdV equation . The periodic KP solutions include directional spreading in the wave field: y η...of the nonlinear preprocessor in the new approach for obtaining numerical solutions to nonlinear wave equations . I will now do so, but without many...analytical study and extremely fast numerical integration of the extended nonlinear Schroedinger equation for fully three dimensional wave motion

  7. Compression Dynamics of an Indirect Drive Fast Ignition Target

    NASA Astrophysics Data System (ADS)

    Stephens, R. B.; Hatchett, S. A.; Turner, R. E.; Tanaka, K. A.; Kodama, R.; Soures, J.

    2002-11-01

    We have compared the compression of an indirectly driven cone-in-shell target, a type proposed for the fast ignition concept, with models. The experimental parameters -500 μm diameter plastic shell with 60 μm thick wall were a 1/5 scale realization of a fast ignition target designed for NIF (absorbing 180 kJ for compression and ˜30 kJ for ignition, and yielding ˜30 MJ) [1]. The implosion was backlit with 6.4 keV x-rays, and observed with a framing camera which captured the implosion from ˜2.6 to 3.3 ns after the onset. The collapsing structure was very similar to model predictions except that non-thermal m-band emissions from the hohlraum penetrated the shell and vaporized gold off the reentrant cone. This could be eliminated by changing the hohlraum composition. [1] S. Hatchett, et al., 5th Wkshp on Fast Ignition of Fusion Targets (Satellite Wkshp, 28th EPS Conf. on Contr. Fusion and Plasma Phys.), Madeira, Portugal (2001).

  8. The influence of cell growth and enzyme activity changes on intracellular metabolite dynamics in AGE1.HN.AAT cells.

    PubMed

    Rath, Alexander G; Rehberg, Markus; Janke, Robert; Genzel, Yvonne; Scholz, Sebastian; Noll, Thomas; Rose, Thomas; Sandig, Volker; Reichl, Udo

    2014-05-20

    Optimization of bioprocesses with mammalian cells mainly concentrates on cell engineering, cell screening and medium optimization to achieve enhanced cell growth and productivity. For improving cell lines by cell engineering techniques, in-depth understandings of the regulation of metabolism and product formation as well as the resulting demand for the different medium components are needed. In this work, the relationship of cell specific growth and uptake rates and of changes in maximum in vitro enzyme activities with intracellular metabolite pools of glycolysis, pentose phosphate pathway, citric acid cycle and energy metabolism were determined for batch cultivations with AGE1.HN.AAT cells. Results obtained by modeling cell growth and consumption of main substrates showed that the dynamics of intracellular metabolite pools is primarily linked to the dynamics of specific glucose and glutamine uptake rates. By analyzing maximum in vitro enzyme activities we found low activities of pyruvate dehydrogenase and pyruvate carboxylase which suggest a reduced metabolite transfer into the citric acid cycle resulting in lactate release (Warburg effect). Moreover, an increase in the volumetric lactate production rate during the transition from exponential to stationary growth together with a transient accumulation of fructose 1,6-bisphosphate, fructose 1-phosphate and ribose 5-phosphate point toward an upregulation of PK via FBP. Glutaminase activity was about 44-fold lower than activity of glutamine synthetase. This seemed to be sufficient for the supply of intermediates for biosynthesis but might lead to unnecessary dissipation of ATP. Taken together, our results elucidate regulation of metabolic networks of immortalized mammalian cells by changes of metabolite pools over the time course of batch cultivations. Eventually, it enables the use of cell engineering strategies to improve the availability of building blocks for biomass synthesis by increasing glucose as well as

  9. Dual effects of chlorobutanol on secretory response and intracellular Ca2+ dynamics in isolated pancreatic acini of the rat.

    PubMed Central

    Habara, Y.; Kanno, T.

    1993-01-01

    1. The effects of chlorobutanol, a widely used drug preservative, on exocrine response and intracellular Ca2+ dynamics were examined in isolated pancreatic acini of the rat. 2. Chlorobutanol (1 mg ml-1) markedly inhibited the secretory response to cholecystokinin octapeptide (CCK-8), carbamylcholine chloride (carbachol), or sodium fluoride, a direct G-protein activator. However, chlorobutanol itself induced a maximal release of amylase when the dose was increased to 4 mg ml-1. 3. An oscillatory fluctuation of cytoplasmic Ca2+ concentration, [Ca2+]c, induced by 5 pM CCK-8 or 0.3 microM carbachol was totally abolished in the presence of 1 mg ml-1 chlorobutanol. 4. A biphasic change in [Ca2+]c induced by 100 pM CCK-8, a rapid rise followed by a gradual decay, was transformed to an oscillatory fluctuation by the preservative. 5. Chlorobutanol inhibited 13 pM [125I]-CCK-8 or 0.5 nM [3H]-methylscopolamine chloride binding to the acinar cells in a dose-dependent manner. 6. These results indicate that chlorobutanol produces discernible pharmacological effects on the secretory response in rat pancreatic acinar cells through changes in the Ca2+ dynamics. Possible sites of action could be at a binding process of secretagogues to their receptors, at an activation process of a G-protein located in the plasma membrane, or at the processes following G-protein activation. However, the possibility that the preservative may distort the Ca(2+)-transport function of the plasma membrane or the membrane of intracellular organella, especially Ca(2+)-sequestering pools, cannot be excluded. PMID:7689400

  10. Creatine loading elevates the intracellular phosphorylation potential and alters adaptive responses of rat fast-twitch muscle to chronic low-frequency stimulation.

    PubMed

    Putman, Charles T; Gallo, Maria; Martins, Karen J B; MacLean, Ian M; Jendral, Michelle J; Gordon, Tessa; Syrotuik, Daniel G; Dixon, Walter T

    2015-07-01

    This study tested the hypothesis that elevating the intracellular phosphorylation potential (IPP = [ATP]/[ADP]free) within rat fast-twitch tibialis anterior muscles by creatine (Cr) loading would prevent fast-to-slow fibre transitions induced by chronic low-frequency electrical stimulation (CLFS, 10 Hz, 12 h/day). Creatine-control and creatine-CLFS groups drank a solution of 1% Cr + 5% dextrose, ad libitum, for 10 days before and during 10 days of CLFS; dextrose-control and dextrose-CLFS groups drank 5% dextrose. Cr loading increased total Cr (P < 0.025), phosphocreatine (PCr) (P < 0.003), and the IPP (P < 0.0008) by 34%, 45%, and 64%, respectively. PCr and IPP were 46% (P < 0.002) and 76% (P < 0.02) greater in creatine-CLFS than in dextrose-CLFS. Higher IPP was confirmed by a 58% reduction in phospho-AMP-activated protein kinase α (Thr172) (P < 0.006). In dextrose-CLFS, myosin heavy chain (MyHC) I and IIa transcripts increased 32- and 38-fold (P < 0.006), respectively, whereas MyHC-IIb mRNA decreased by 75% (P < 0.03); the corresponding MyHC-I and MyHC-IIa protein contents increased by 2.0- (P < 0.03) and 2.7-fold (P < 0.05), respectively, and MyHC-IIb decreased by 30% (P < 0.03). In contrast, within creatine-CLFS, MyHC-I and MyHC-IIa mRNA were unchanged and MyHC-IIb mRNA decreased by 75% (P < 0.003); the corresponding MyHC isoform contents were not altered. Oxidative reference enzymes were similarly elevated (P < 0.01) in dextrose-CLFS and creatine-CLFS, but reciprocal reductions in glycolytic reference enzymes occurred only in dextrose-CLFS (P < 0.02). Preservation of the glycolytic potential and greater SERCA2 and parvalbumin contents in creatine-CLFS coincided with prolonged time to peak tension and half-rise time (P < 0.01). These results highlight the IPP as an important physiological regulator of muscle fibre plasticity and demonstrate that training-induced changes typically associated with improvements in muscular endurance or increased power output are

  11. Fast phonon dynamics of a nanomechanical oscillator due to cooperative effects

    NASA Astrophysics Data System (ADS)

    Ceban, Victor; Longo, Paolo; Macovei, Mihai A.

    2017-02-01

    We investigate the coupled-system dynamics of two-level quantum dots placed on a vibrating nanomechanical resonator. The ensemble of quantum dots exhibits superradiance features which are transferred to the mechanical degrees of freedom representing fast quantum dynamics and enhanced phonon emission in a nanomechanical setup, resembling the superradiance effect.

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    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 (6×105 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. PMID:27941600

  14. Simulating fast and slow dynamic effects in power systems

    SciTech Connect

    de Mello, F.P.; Feltes, J.W.; Laskowski, T.F.; Oppel, L.J. )

    1992-07-01

    Electric power systems comprise a nearly infinite number of devices, exhibiting dynamic characteristics in a wide range of bandwidths and with significant nonlinear effects. Historically, the nature of these devices, the robust configuration of the electric power system, and its loading were such that the interaction between devices became relatively unimportant in system performance several seconds after disturbances. Greater utilization of electric plant, through heavier system loadings, interconnections, and increasing use of controls, has at times necessitated predictions of system performance through simulation extending over a time range of tens of seconds to several minutes. The phenomena occurring over this extended time frame has been referred to as long-term dynamics. There are basically two classes of problems involving long-term dynamics. One is the problem of islanding with significant imbalances between load and generation where prime mover action in response to frequency deviations is significant. The other concerns problems of insufficient damping and/or synchronizing power, and voltage collapse.

  15. Nanocluster dynamics in fast rate epitaxy under mesoplasma condition

    NASA Astrophysics Data System (ADS)

    Chen, L. W.; Shibuta, Y.; Kambara, M.; Yoshida, T.

    2013-03-01

    The dynamics of Si nano-clusters during epitaxial growth has been investigated with molecular dynamics simulation using the Tersoff potential. Several nm sized Si cluster formed during rapid cooling was found to deform instantaneously upon impingement on a Si(1 0 0) substrate at the same time with the spontaneous ordering of the atomic structure to that of the substrate. Due to the increased fraction of high-energy atoms at the surface, smaller clusters (˜1 nm) are favorable for such a deformation even at lower temperatures. This is the advantage of loosely-bound cluster as growth precursor to attain epitaxy with reduced impact energies.

  16. Dendritic diameters affect the spatial variability of intracellular calcium dynamics in computer models

    PubMed Central

    Anwar, Haroon; Roome, Christopher J.; Nedelescu, Hermina; Chen, Weiliang; Kuhn, Bernd; De Schutter, Erik

    2014-01-01

    There is growing interest in understanding calcium dynamics in dendrites, both experimentally and computationally. Many processes influence these dynamics, but in dendrites there is a strong contribution of morphology because the peak calcium levels are strongly determined by the surface to volume ratio (SVR) of each branch, which is inversely related to branch diameter. In this study we explore the predicted variance of dendritic calcium concentrations due to local changes in dendrite diameter and how this is affected by the modeling approach used. We investigate this in a model of dendritic calcium spiking in different reconstructions of cerebellar Purkinje cells and in morphological analysis of neocortical and hippocampal pyramidal neurons. We report that many published models neglect diameter-dependent effects on calcium concentration and show how to implement this correctly in the NEURON simulator, both for phenomenological pool based models and for implementations using radial 1D diffusion. More detailed modeling requires simulation of 3D diffusion and we demonstrate that this does not dissipate the local concentration variance due to changes of dendritic diameter. In many cases 1D diffusion of models of calcium buffering give a good approximation provided an increased morphological resolution is implemented. PMID:25100945

  17. Volumetric imaging of fast biological dynamics in deep tissue via wavefront engineering

    NASA Astrophysics Data System (ADS)

    Kong, Lingjie; Tang, Jianyong; Cui, Meng

    2016-03-01

    To reveal fast biological dynamics in deep tissue, we combine two wavefront engineering methods that were developed in our laboratory, namely optical phase-locked ultrasound lens (OPLUL) based volumetric imaging and iterative multiphoton adaptive compensation technique (IMPACT). OPLUL is used to generate oscillating defocusing wavefront for fast axial scanning, and IMPACT is used to compensate the wavefront distortions for deep tissue imaging. We show its promising applications in neuroscience and immunology.

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

    NASA Technical Reports Server (NTRS)

    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).

  19. Precision and Fast Wavelength Tuning of a Dynamically Phase-Locked Widely-Tunable Laser

    NASA Technical Reports Server (NTRS)

    Numata, Kenji; Chen, Jeffrey R.; Wu, Stewart T.

    2012-01-01

    We report a precision and fast wavelength tuning technique demonstrated for a digital-supermode distributed Bragg reflector laser. The laser was dynamically offset-locked to a frequency-stabilized master laser using an optical phase-locked loop, enabling precision fast tuning to and from any frequencies within a 40-GHz tuning range. The offset frequency noise was suppressed to the statically offset-locked level in less than 40 s upon each frequency switch, allowing the laser to retain the absolute frequency stability of the master laser. This technique satisfies stringent requirements for gas sensing lidars and enables other applications that require such well-controlled precision fast tuning.

  20. Dynamics of intracellular polymers in enhanced biological phosphorus removal processes under different organic carbon concentrations.

    PubMed

    Xing, Lizhen; Ren, Li; Tang, Bo; Wu, Guangxue; Guan, Yuntao

    2013-01-01

    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.

  1. Rapid intracellular motility and dynamic membrane events in an Antarctic foraminifer.

    PubMed

    Bowser, S S; DeLaca, T E

    1985-10-01

    Some properties of cytoplasmic transport in a cold-adapted (Antarctic) organism are reported for the first time. Phase-contrast light microscopy of Astrammina rara, an arenaceous foraminiferan protozoan, reveals that the saltatory transport of cytoplasmic granules in reticulopods occurs bidirectionally and at rates up to 7.5-micron/s. Extracellularly attached latex microspheres are rapidly translocated on the reticulopodial surface, thus demonstrating membrane fluidity at low (-1.8 degrees C) ambient temperatures. Rapid extension/withdrawal and branching/fusing of pseudopodia further illustrate dynamic plasma membrane activity at subzero temperatures. Immunofluorescence microscopy with an antibody monospecific for tubulin shows that these pseudopods contain microtubules. The motility of this cold-adapted foraminifer therefore appears fully comparable to the motility of allogromiid foraminifers from temperate waters.

  2. Dynamic speckle-interferometer for intracellular processes analyses at high optical magnification

    NASA Astrophysics Data System (ADS)

    Baharev, A. A.; Vladimirov, A. P.; Malygin, A. S.; Mikhailova, Y. A.; Novoselova, I. A.; Yakin, D. I.; Druzhinin, A. V.

    2015-05-01

    At present work dynamic of biospeckles is used for studying processes occurring in cells which arranged in the one layer. The basis of many diseases is changes in the structural and functional properties of the molecular cells components as caused by the influence of external factors and internal functional disorders. Purpose of work is approbation of speckle-interferometer designed for the analysis of cellular metabolism in individual cells. As a parameter, characterizing the metabolic activity of cells used the value of the correlation coefficient (η) of optical signals proportional to the radiation intensity I, recorded at two points in time t. At 320x magnification for the cell diameter of 20 microns value η can be determined in the area size of 6 microns.

  3. Three dimensional MOF-sponge for fast dynamic adsorption.

    PubMed

    Li, Huizeng; Li, Mingzhu; Li, Wenbo; Yang, Qiang; Li, Yanan; Gu, Zhenkun; Song, Yanlin

    2017-02-22

    Nowadays, environmental pollution is a big problem. Metal organic frameworks (MOFs) provide a novel strategy for exhaust gases adsorption and toxic pollutants removal. We proposed a facile and versatile method to prepare a highly efficient three dimensional MOF-sponge by coating MOF crystals on polyurethane sponge surface, mimicking the porous structure of the marine animal, sponge. Owing to combination of the spatial structure of the commercial sponge and the excellent adsorption capacity of MOF coatings, the MOF-sponge possessed good permeability and high dynamic adsorption capacity. Dynamic adsorption ability of the prepared Cu3(BTC)2-sponge was demonstrated by flowing gas-mixtures of NH3/N2 and an aquatic solution of Rhodamine B through it, with a capacity of 101.6 mg g(-1) and 8.8 mg g(-1) for NH3 and Rhodamine B, respectively.

  4. Nonadiabatic quantum state engineering driven by fast quench dynamics

    NASA Astrophysics Data System (ADS)

    Herrera, Marcela; Sarandy, Marcelo S.; Duzzioni, Eduardo I.; Serra, Roberto M.

    2014-02-01

    There are a number of tasks in quantum information science that exploit nontransitional adiabatic dynamics. Such a dynamics is bounded by the adiabatic theorem, which naturally imposes a speed limit in the evolution of quantum systems. Here, we investigate an approach for quantum state engineering exploiting a shortcut to the adiabatic evolution, which is based on rapid quenches in a continuous-time Hamiltonian evolution. In particular, this procedure is able to provide state preparation faster than the adiabatic brachistochrone. Remarkably, the evolution time in this approach is shown to be ultimately limited by its "thermodynamical cost," provided in terms of the average work rate (average power) of the quench process. We illustrate this result in a scenario that can be experimentally implemented in a nuclear magnetic resonance setup.

  5. Fast parallel algorithms for short-range molecular dynamics

    SciTech Connect

    Plimpton, S.

    1993-05-01

    Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a subset of atoms; the second assigns each a subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently -- those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 10,000,000 atoms on three parallel supercomputers, the nCUBE 2, Intel iPSC/860, and Intel Delta. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and the Intel Delta performs about 30 times faster than a single Y-MP processor and 12 times faster than a single C90 processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

  6. High resolution and dynamic imaging of biopersistence and bioreactivity of extra and intracellular MWNTs exposed to microglial cells

    PubMed Central

    Gonzalez Carter, Daniel A.; Motskin, Michael; Pienaar, Ilse S.; Chen, Shu; Hu, Sheng; Ruenraroengsak, Pakatip; Ryan, Mary P.; Shaffer, Milo S. P.; Dexter, David T.

    2016-01-01

    Multi-walled carbon nanotubes (MWNTs) are increasingly being developed both as neuro-therapeutic drug delivery systems to the brain and as neural scaffolds to drive tissue regeneration across lesion sites. MWNTs with different degrees of acid oxidation may have different bioreactivities and propensities to aggregate in the extracellular environment, and both individualised and aggregated MWNTs may be expected to be found in the brain. Before practical application, it is vital to understand how both aggregates and individual MWNTs will interact with local phagocytic immune cells, the microglia, and ultimately to determine their biopersistence in the brain. The processing of extra- and intracellular MWNTs (both pristine and when acid oxidised) by microglia was characterised across multiple length scales by correlating a range of dynamic, quantitative and multi-scale techniques, including: UV-vis spectroscopy, light microscopy, focussed ion beam scanning electron microscopy and transmission electron microscopy. Dynamic, live cell imaging revealed the ability of microglia to break apart and internalise micron-sized extracellular agglomerates of acid oxidised MWNT, but not pristine MWNTs. The total amount of MWNTs internalised by, or strongly bound to, microglia was quantified as a function of time. Neither the significant uptake of oxidised MWNTs, nor the incomplete uptake of pristine MWNTs affected microglial viability, pro-inflammatory cytokine release or nitric oxide production. However, after 24 hrs exposure to pristine MWNTs, a significant increase in the production of reactive oxygen species was observed. Small aggregates and individualised oxidised MWNTs were present in the cytoplasm and vesicles, including within multilaminar bodies, after 72 hours. Some evidence of morphological damage to oxidised MWNT structure was observed including highly disordered graphitic structures, suggesting possible biodegradation. This work demonstrates the utility of dynamic

  7. Intracellular dynamics of archaeal FANCM homologue Hef in response to halted DNA replication.

    PubMed

    Lestini, Roxane; Laptenok, Sergey P; Kühn, Joëlle; Hink, Mark A; Schanne-Klein, Marie-Claire; Liebl, Ursula; Myllykallio, Hannu

    2013-12-01

    Hef is an archaeal member of the DNA repair endonuclease XPF (XPF)/Crossover junction endonuclease MUS81 (MUS81)/Fanconi anemia, complementation group M (FANCM) protein family that in eukaryotes participates in the restart of stalled DNA replication forks. To investigate the physiological roles of Hef in maintaining genome stability in living archaeal cells, we studied the localization of Hef-green fluorescent protein fusions by fluorescence microscopy. Our studies revealed that Haloferax volcanii Hef proteins formed specific localization foci under regular growth conditions, the number of which specifically increased in response to replication arrest. Purification of the full-length Hef protein from its native host revealed that it forms a stable homodimer in solution, with a peculiar elongated configuration. Altogether our data indicate that the shape of Hef, significant physicochemical constraints and/or interactions with DNA limit the apparent cytosolic diffusion of halophilic DNA replication/repair complexes, and demonstrate that Hef proteins are dynamically recruited to archaeal eukaryotic-like chromatin to counteract DNA replication stress. We suggest that the evolutionary conserved function of Hef/FANCM proteins is to enhance replication fork stability by directly interacting with collapsed replication forks.

  8. Dynamic expression and heterogeneous intracellular location of En-1 during late mouse embryonic development.

    PubMed

    Zhong, Shan-chuan; Chen, Xing-shu; Cai, Qi-yan; Luo, Xue; Chen, Xing-hua; Liu, Jing; Yao, Zhong-xiang

    2010-01-01

    Engrailed-1 (En-1) is a transcription factor involved in the development of the midbrain/hindbrain during mouse early embryogenesis. Although En-1 is expressed from embryogenesis to adulthood, there has been no detailed description of its expression during late mouse embryonic development. Here we report the expression pattern of En-1 in the mouse embryo from E10.5 to the neonatal state. With immunohistochemistry we found that En-1 was expressed in the central nervous system (CNS) from E10.5 to the neonatal state, mostly restricted to the midbrain/hindbrain junction. Outside the CNS, En-1 is dynamically expressed in several neural crest-associated structures including the cranial mesenchyme, the mandibular arches, the vagus nerve, the dorsal root ganglia, the sympathetic ganglia, the somites, the heart and the cloaca. Additionally, we found that in the CNS, most of the En-1 was located in the nuclei, while outside the CNS, En-1 was mainly expressed in the cytoplasm. These findings provided additional evidence that En-1 may be involved in the development of neural crest cells.

  9. Flood Regime Dynamics with Slow-Fast Landscape-Climate Feedbacks

    NASA Astrophysics Data System (ADS)

    Perdigão, Rui A. P.; Blöschl, Günter

    2015-04-01

    The dynamical evolution of flood regimes is evaluated in the general case whereby floods interact nonlinearly with coevolving climate and landscape factors at different scales. For that purpose, a spatiotemporal analysis of the dynamic flood response to precipitation changes is conducted and a slow-fast nonlinear dynamical model is built linking flood regime dynamics with climate, landscape 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). A dynamic 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 scale interaction between slow and fast dynamics, represented respectively by spatial and temporal characteristics of the hydroclimate dynamics. The spatiotemporal analysis shows that in general floods are more responsive to spatial (regional) than to temporal (decadal) variability in its dominant controls, except in stable hydroclimatic regions. In fact, on one hand catchments from stable dry lowlands and high wetlands exhibit similarity between spatial and temporal relative rates of change (spatiotemporal symmetry) and low landscape-climate codependence, suggesting they are not coevolving significantly. On the other hand, intermediate, dynamically evolving regions show differences between those sensitivities (symmetry breaks) and higher landscape-climate codependence, in line with undergoing coevolution. The break of symmetry is an emerging behaviour from nonlinear dynamic feedbacks within the hydroclimate system. The dynamical model captures emerging features of the flood regime dynamics and nonlinear landscape-climate feedbacks, supporting the assessment of spatiotemporally asymmetric flood change. Moreover, it informs on the precipitation and

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

    PubMed

    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.

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

    PubMed Central

    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

  12. Fast Distributed Dynamics of Semantic Networks via Social Media.

    PubMed

    Carrillo, Facundo; Cecchi, Guillermo A; Sigman, Mariano; Slezak, Diego Fernández

    2015-01-01

    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.

  13. Fast Distributed Dynamics of Semantic Networks via Social Media

    PubMed Central

    Carrillo, Facundo; Cecchi, Guillermo A.; Sigman, Mariano; Fernández Slezak, Diego

    2015-01-01

    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. PMID:26074953

  14. Intracellular Dialysis Disrupts Zn2+ Dynamics and Enables Selective Detection of Zn2+ Influx in Brain Slice Preparations

    PubMed Central

    Aiba, Isamu; West, Adrian K; Sheline, Christian T; Shuttleworth, C. William

    2013-01-01

    We examined the impact of intracellular dialysis on fluorescence detection of neuronal intracellular Zn2+ accumulation. Comparison between two dialysis conditions (standard; 20minutes, brief; 2minutes) by standard whole-cell clamp revealed a high vulnerability of intracellular Zn2+ buffers to intracellular dialysis. Thus low concentrations of zinc-pyrithione generated robust responses in neurons with standard dialysis, but signals were smaller in neurons with short dialysis. Release from oxidation-sensitive Zn2+ pools were reduced by standard dialysis, when compared with responses in neurons with brief dialysis. The dialysis effects were partly reversed by inclusion of recombinant metallothionein-3 in the dialysis solution. These findings suggested that extensive dialysis could be exploited for selective detection of transmembrane Zn2+ influx. Different dialysis conditions were then used to probe responses to synaptic stimulation. Under standard dialysis conditions, synaptic stimuli generated significant FluoZin-3 signals in wild-type (WT) preparations, but responses were almost absent in preparations lacking vesicular Zn2+ (ZnT3-KO). In contrast, under brief dialysis conditions, intracellular Zn2+ transients were very similar in WT and ZnT3-KO preparations. This suggests that both intracellular release and transmembrane flux can contribute to intracellular Zn2+ accumulation after synaptic stimulation. These results demonstrate significant confounds and potential use of intracellular dialysis to investigate intracellular Zn2+ accumulation mechanisms. PMID:23517525

  15. Fast characterization of cheeses by dynamic headspace-mass spectrometry.

    PubMed

    Pérès, Christophe; Denoyer, Christian; Tournayre, Pascal; Berdagué, Jean-Louis

    2002-03-15

    This study describes a rapid method to characterize cheeses by analysis of their volatile fraction using dynamic headspace-mass spectrometry. Major factors governing the extraction and concentration of the volatile components were first studied. These components were extracted from the headspace of the cheeses in a stream of helium and concentrated on a Tenax TA trap. They were then desorbed by heating and injected directly into the source of a mass spectrometer via a short deactivated silica transfer line. The mass spectra of the mixture of volatile components were considered as fingerprints of the analyzed substances. Forward stepwise factorial discriminant analysis afforded a limited number of characteristic mass fragments that allowed a good classification of the batches of cheeses studied.

  16. Fast Search for Dynamic Multi-Relational Graphs

    SciTech Connect

    Choudhury, Sutanay; Holder, Larry; Chin, George; Feo, John T.

    2013-06-23

    Acting on time-critical events by processing ever growing social media or news streams is a major technical challenge. Many of these data sources can be modeled as multi-relational graphs. Continuous queries or techniques to search for rare events that typically arise in monitoring applications have been studied extensively for relational databases. This work is dedicated to answer the question that emerges naturally: how can we efficiently execute a continuous query on a dynamic graph? This paper presents an exact subgraph search algorithm that exploits the temporal characteristics of representative queries for online news or social media monitoring. The algorithm is based on a novel data structure called the that leverages the structural and semantic characteristics of the underlying multi-relational graph. The paper concludes with extensive experimentation on several real-world datasets that demonstrates the validity of this approach.

  17. Gas dynamic theory of flight of fast electron flux in plasma

    NASA Astrophysics Data System (ADS)

    Melnik, V. N.

    The one-dimensional flight of a fast electron flux in plasma is investigated taking into account generation and absorption of plasma waves. The transition from the kinetic description to the gas dynamics is made. The closed set of gas dynamic equations for electrons and plasmons is derived and an automodel solution is obtained in the case of instantaneous injection. This solution represents the beam-plasma formation on natural oscillations in the system electrons+plasmons is considered.

  18. The effect of temperature on the coupled slow and fast dynamics of an electrochemical oscillator

    PubMed Central

    Zülke, Alana A.; Varela, Hamilton

    2016-01-01

    The coupling among disparate time-scales is ubiquitous in many chemical and biological systems. We have recently investigated the effect of fast and, long-term, slow dynamics in surface processes underlying some electrocatalytic reactions. Herein we report on the effect of temperature on the coupled slow and fast dynamics of a model system, namely the electro-oxidation of formic acid on platinum studied at five temperatures between 5 and 45 °C. The main result was a turning point found at 25 °C, which clearly defines two regions for the temperature dependency on the overall kinetics. In addition, the long-term evolution allowed us to compare reaction steps related to fast and slow evolutions. Results were discussed in terms of the key role of PtO species, which chemically couple slow and fast dynamics. In summary we were able to: (a) identify the competition between two reaction steps as responsible for the occurrence of two temperature domains; (b) compare the relative activation energies of these two steps; and (c) suggest the role of a given reaction step on the period-increasing set of reactions involved in the oscillatory dynamics. The introduced methodology could be applied to other systems to uncover the temperature dependence of complex chemical networks. PMID:27079514

  19. The effect of temperature on the coupled slow and fast dynamics of an electrochemical oscillator

    NASA Astrophysics Data System (ADS)

    Zülke, Alana A.; Varela, Hamilton

    2016-04-01

    The coupling among disparate time-scales is ubiquitous in many chemical and biological systems. We have recently investigated the effect of fast and, long-term, slow dynamics in surface processes underlying some electrocatalytic reactions. Herein we report on the effect of temperature on the coupled slow and fast dynamics of a model system, namely the electro-oxidation of formic acid on platinum studied at five temperatures between 5 and 45 °C. The main result was a turning point found at 25 °C, which clearly defines two regions for the temperature dependency on the overall kinetics. In addition, the long-term evolution allowed us to compare reaction steps related to fast and slow evolutions. Results were discussed in terms of the key role of PtO species, which chemically couple slow and fast dynamics. In summary we were able to: (a) identify the competition between two reaction steps as responsible for the occurrence of two temperature domains; (b) compare the relative activation energies of these two steps; and (c) suggest the role of a given reaction step on the period-increasing set of reactions involved in the oscillatory dynamics. The introduced methodology could be applied to other systems to uncover the temperature dependence of complex chemical networks.

  20. Fast Dynamical Evolution of Hadron Resonance Gas via Hagedorn States

    NASA Astrophysics Data System (ADS)

    Beitel, M.; Gallmeister, K.; Greiner, C.

    2017-01-01

    Hagedorn states (HS) are a tool to model the hadronization process which occurs in the phase transition region between the quark gluon plasma (QGP) and the hadron resonance gas (HRG). These states are believed to appear near the Hagedorn temperature TH which in our understanding equals the critical temperature Tc . A covariantly formulated bootstrap equation is solved to generate the zoo of these particles characterized baryon number B, strangeness S and electric charge Q. These hadron-like resonances are characterized by being very massive and by not being limited to quantum numbers of known hadrons. All hadronic properties like masses, spectral functions etc. are taken from the hadronic transport model Ultra Relativistic Quantum Molecular Dynamics (UrQMD). Decay chains of single Hagedorn states provide a well description of experimentally observed multiplicity ratios of strange and multi-strange particles as the Ξ0- and the Ω‑-baryon. In addition, the final energy spectra of resulting hadrons show a thermal-like distribution with the characteristic Hagedorn temperature TH . Box calculations including these Hagedorn states are performed. Indeed, the time scales leading to equilibration of the system are drastically reduced down to 2. . . 5 fm/c.

  1. Fast rendering of forest ecosystems with dynamic global illumination

    NASA Astrophysics Data System (ADS)

    Steele, Jay Edward

    Real-time rendering of large-scale, forest ecosystems remains a challenging problem, in that important global illumination effects, such as leaf transparency and inter-object light scattering, are difficult to capture, given tight timing constraints and scenes that typically contain hundreds of millions of primitives. We propose a new lighting model, adapted from a model previously used to light convective clouds and other participating media, together with GPU ray tracing, in order to achieve these global illumination effects while maintaining near real-time performance. The lighting model is based on a lattice-Boltzmann method in which reflectance, transmittance, and absorption parameters are taken from measurements of real plants. The lighting model is solved as a preprocessing step, requires only seconds on a single GPU, and allows dynamic lighting changes at run-time. The ray tracing engine, which runs on one or multiple GPUs, combines multiple acceleration structures to achieve near real-time performance for large, complex scenes. Both the preprocessing step and the ray tracing engine make extensive use of NVIDIA's Compute Unified Device Architecture (CUDA).

  2. Intracellular proteoglycans.

    PubMed Central

    Kolset, Svein Olav; Prydz, Kristian; Pejler, Gunnar

    2004-01-01

    Proteoglycans (PGs) are proteins with glycosaminoglycan chains, are ubiquitously expressed and have a wide range of functions. PGs in the extracellular matrix and on the cell surface have been the subject of extensive structural and functional studies. Less attention has so far been given to PGs located in intracellular compartments, although several reports suggest that these have biological functions in storage granules, the nucleus and other intracellular organelles. The purpose of this review is, therefore, to present some of these studies and to discuss possible functions linked to PGs located in different intracellular compartments. Reference will be made to publications relevant for the topics we present. It is beyond the scope of this review to cover all publications on PGs in intracellular locations. PMID:14759226

  3. Fast-track extreme event attribution: How fast can we disentangle thermodynamic (forced) and dynamic (internal) contributions?

    NASA Astrophysics Data System (ADS)

    Haustein, Karsten; Otto, Friederike; Uhe, Peter; Allen, Myles; Cullen, Heidi

    2016-04-01

    provide sufficient guidance to determine the dynamic contribution to the event on the basis of monthly mean values. No such link can be made (North Atlantic/Western Europe region) for shorter time-scales, unless the observed state of the circulation is taken as reference for the model analysis (e.g. Christidis et al. 2014). We present results from our most recent attribution analysis for the December 2015 UK floods (Storm Desmond and Eva), during which we find a robust teleconnection link between Pacific SSTs and North Atlantic Jetstream anomalies. This is true for both experiments, with forecast and observed SSTs. We propose a fast and simple analysis method based on the comparison of current climatological circulation patterns with actual and natural conditions. Alternative methods are discussed and analysed regarding their potential for fast-track attribution of the role of dynamics. Also, we briefly revisit the issue of internal vs forced dynamic contributions.

  4. Intracellular Accumulation of Glycine in Polyphosphate-Accumulating Organisms in Activated Sludge, a Novel Storage Mechanism under Dynamic Anaerobic-Aerobic Conditions

    PubMed Central

    Nguyen, Hien Thi Thu; Kristiansen, Rikke; Vestergaard, Mette; Wimmer, Reinhard

    2015-01-01

    Dynamic anaerobic-aerobic feast-famine conditions are applied to wastewater treatment plants to select polyphosphate-accumulating organisms to carry out enhanced biological phosphorus removal. Acetate is a well-known substrate to stimulate this process, and here we show that different amino acids also are suitable substrates, with glycine as the most promising. 13C-labeled glycine and nuclear magnetic resonance (NMR) were applied to investigate uptake and potential storage products when activated sludge was fed with glycine under anaerobic conditions. Glycine was consumed by the biomass, and the majority was stored intracellularly as free glycine and fermentation products. Subsequently, in the aerobic phase without addition of external substrate, the stored glycine was consumed. The uptake of glycine and oxidation of intracellular metabolites took place along with a release and uptake of orthophosphate, respectively. Fluorescence in situ hybridization combined with microautoradiography using 3H-labeled glycine revealed uncultured actinobacterial Tetrasphaera as a dominant glycine consumer. Experiments with Tetrasphaera elongata as representative of uncultured Tetrasphaera showed that under anaerobic conditions it was able to take up labeled glycine and accumulate this and other labeled metabolites to an intracellular concentration of approximately 4 mM. All components were consumed under subsequent aerobic conditions. Intracellular accumulation of amino acids seems to be a novel storage strategy for polyphosphate-accumulating bacteria under dynamic anaerobic-aerobic feast-famine conditions. PMID:25956769

  5. Structural dynamics of soluble chloride intracellular channel protein CLIC1 examined by amide hydrogen-deuterium exchange mass spectrometry.

    PubMed

    Stoychev, Stoyan H; Nathaniel, Christos; Fanucchi, Sylvia; Brock, Melissa; Li, Sheng; Asmus, Kyle; Woods, Virgil L; Dirr, Heini W

    2009-09-08

    Chloride intracellular channel protein 1 (CLIC1) functions as an anion channel in plasma and nuclear membranes when its soluble monomeric form converts to an integral-membrane form. The transmembrane region of CLIC1 is located in its thioredoxin-like domain 1, but the mechanism whereby the protein converts to its membrane conformation has yet to be determined. Since channel formation in membranes is enhanced at low pH (5 to 5.5), a condition that is found at the surface of membranes, the structural dynamics of soluble CLIC1 was studied at pH 7 and at pH 5.5 in the absence of membranes by amide hydrogen-deuterium exchange mass spectrometry (DXMS). Rapid hydrogen exchange data indicate that CLIC1 displays a similar core structure at these pH values. Domain 1 is less stable than the all-helical domain 2, and, while the structure of domain 1 remains intact, its conformational flexibility is further increased in an acidic environment (pH 5.5). In the absence of membrane, an acidic environment appears to prime the solution structure of CLIC1 by destabilizing domain 1 in order to lower the activation energy barrier for its conversion to the membrane-insertion conformation. The significantly enhanced H/D-exchange rates at pH 5.5 displayed by two segments (peptides 11-31 and 68-82) could be due to the protonation of acidic residues in salt bridges. One of these segments (peptide 11-31) includes part of the transmembrane region which, in the solution structure, consists of helix alpha1. This helix is intrinsically stable and is most likely retained in the membrane conformation. Strand beta2, another element of the transmembrane region, displays a propensity to form a helical structure and has putative N- and C-capping motifs, suggesting that it too most likely forms a helix in a lipid bilayer.

  6. Precision and fast wavelength tuning of a dynamically phase-locked widely-tunable laser.

    PubMed

    Numata, Kenji; Chen, Jeffrey R; Wu, Stewart T

    2012-06-18

    We report a precision and fast wavelength tuning technique demonstrated for a digital-supermode distributed Bragg reflector laser. The laser was dynamically offset-locked to a frequency-stabilized master laser using an optical phase-locked loop, enabling precision fast tuning to and from any frequencies within a ~40-GHz tuning range. The offset frequency noise was suppressed to the statically offset-locked level in less than ~40 μs upon each frequency switch, allowing the laser to retain the absolute frequency stability of the master laser. This technique satisfies stringent requirements for gas sensing lidars and enables other applications that require such well-controlled precision fast tuning.

  7. Dynamic polarizability of tungsten atoms reconstructed from fast electrical explosion of fine wires in vacuum

    SciTech Connect

    Sarkisov, G. S.; Rosenthal, S. E.; Struve, K. W.

    2016-10-12

    For nanosecond electrical explosion of fine metal wires in vacuum generates calibrated, radially expanded gas cylinders of metal atoms are surrounded by low-density fast expanding plasma corona. Here, a novel integrated-phase technique, based on laser interferometry, provides the dynamic dipole polarizability of metal atoms. This data was previously unavailable for tungsten atoms. Furthermore, an extremely high melting temperature and significant pre-melt electronic emission make these measurements particularly complicated for this refractory metal.

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

    SciTech Connect

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

    SciTech Connect

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

    2016-07-01

    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.

  10. Fast imaging technique to study drop impact dynamics of non-Newtonian fluids.

    PubMed

    Xu, Qin; Peters, Ivo; Wilken, Sam; Brown, Eric; Jaeger, Heinrich

    2014-03-05

    In the field of fluid mechanics, many dynamical processes not only occur over a very short time interval but also require high spatial resolution for detailed observation, scenarios that make it challenging to observe with conventional imaging systems. One of these is the drop impact of liquids, which usually happens within one tenth of millisecond. To tackle this challenge, a fast imaging technique is introduced that combines a high-speed camera (capable of up to one million frames per second) with a macro lens with long working distance to bring the spatial resolution of the image down to 10 µm/pixel. The imaging technique enables precise measurement of relevant fluid dynamic quantities, such as the flow field, the spreading distance and the splashing speed, from analysis of the recorded video. To demonstrate the capabilities of this visualization system, the impact dynamics when droplets of non-Newtonian fluids impinge on a flat hard surface are characterized. Two situations are considered: for oxidized liquid metal droplets we focus on the spreading behavior, and for densely packed suspensions we determine the onset of splashing. More generally, the combination of high temporal and spatial imaging resolution introduced here offers advantages for studying fast dynamics across a wide range of microscale phenomena.

  11. Spontaneous emergence of fast attractor dynamics in a model of developing primary visual cortex

    PubMed Central

    Miconi, Thomas; McKinstry, Jeffrey L.; Edelman, Gerald M.

    2016-01-01

    Recent evidence suggests that neurons in primary sensory cortex arrange into competitive groups, representing stimuli by their joint activity rather than as independent feature analysers. A possible explanation for these results is that sensory cortex implements attractor dynamics, although this proposal remains controversial. Here we report that fast attractor dynamics emerge naturally in a computational model of a patch of primary visual cortex endowed with realistic plasticity (at both feedforward and lateral synapses) and mutual inhibition. When exposed to natural images (but not random pixels), the model spontaneously arranges into competitive groups of reciprocally connected, similarly tuned neurons, while developing realistic, orientation-selective receptive fields. Importantly, the same groups are observed in both stimulus-evoked and spontaneous (stimulus-absent) activity. The resulting network is inhibition-stabilized and exhibits fast, non-persistent attractor dynamics. Our results suggest that realistic plasticity, mutual inhibition and natural stimuli are jointly necessary and sufficient to generate attractor dynamics in primary sensory cortex. PMID:27796298

  12. Intracellular accumulation dynamics and fate of zinc ions in alveolar epithelial cells exposed to airborne ZnO nanoparticles at the air–liquid interface

    SciTech Connect

    Mihai, Cosmin; Chrisler, William B.; Xie, Yumei; Hu, Dehong; Szymanski, Craig J.; Tolic, Ana; Klein, Jessica A.; Smith, Jordan N.; Tarasevich, Barbara J.; Orr, Galya

    2013-12-02

    Airborne nanoparticles (NPs) that enter the respiratory tract are likely to reach the alveolar region. Accumulating observations support a role for zinc oxide (ZnO) NP dissolution in toxicity, but the majority of in vitro studies were conducted in cells exposed to NPs in growth media, where large doses of dissolved ions are shed into the exposure solution. To determine the precise intracellular accumulation dynamics and fate of zinc ions (Zn2+) shed by airborne NPs in the cellular environment, we exposed alveolar epithelial cells to aerosolized NPs at the air-liquid interface (ALI). Using a fluorescent indicator for Zn2+, together with organelle-specific fluorescent proteins, we quantified Zn2+ in single cells and organelles over time. We found that at the ALI, intracellular Zn2+ values peaked 3 h post exposure and decayed to normal values by 12 h, while in submersed cultures, intracellular Zn2+ values continued to increase over time. The lowest toxic NP dose at the ALI generated peak intracellular Zn2+ values that were nearly 3 folds lower than the peak values generated by the lowest toxic dose of NPs in submersed cultures, and 8 folds lower than the peak values generated by the lowest toxic dose of ZnSO4 or Zn2+. At the ALI, the majority of intracellular Zn2+ was found in endosomes and lysosomes as early as 1 h post exposure. In contrast, the majority of intracellular Zn2+ following exposures to ZnSO4 was found in other larger vesicles, with less than 10% in endosomes and lysosomes. In conclusion, together, our observations indicate that low but critical levels of intracellular Zn2+ have to be reached, concentrated specifically in endosomes and lysosomes, for toxicity to occur, and point to the focal dissolution of the NPs in the cellular environment and the accumulation of the ions specifically in endosomes and lysosomes as the processes

  13. Intracellular accumulation dynamics and fate of zinc ions in alveolar epithelial cells exposed to airborne ZnO nanoparticles at the air–liquid interface

    DOE PAGES

    Mihai, Cosmin; Chrisler, William B.; Xie, Yumei; ...

    2013-12-02

    Airborne nanoparticles (NPs) that enter the respiratory tract are likely to reach the alveolar region. Accumulating observations support a role for zinc oxide (ZnO) NP dissolution in toxicity, but the majority of in vitro studies were conducted in cells exposed to NPs in growth media, where large doses of dissolved ions are shed into the exposure solution. To determine the precise intracellular accumulation dynamics and fate of zinc ions (Zn2+) shed by airborne NPs in the cellular environment, we exposed alveolar epithelial cells to aerosolized NPs at the air-liquid interface (ALI). Using a fluorescent indicator for Zn2+, together with organelle-specificmore » fluorescent proteins, we quantified Zn2+ in single cells and organelles over time. We found that at the ALI, intracellular Zn2+ values peaked 3 h post exposure and decayed to normal values by 12 h, while in submersed cultures, intracellular Zn2+ values continued to increase over time. The lowest toxic NP dose at the ALI generated peak intracellular Zn2+ values that were nearly 3 folds lower than the peak values generated by the lowest toxic dose of NPs in submersed cultures, and 8 folds lower than the peak values generated by the lowest toxic dose of ZnSO4 or Zn2+. At the ALI, the majority of intracellular Zn2+ was found in endosomes and lysosomes as early as 1 h post exposure. In contrast, the majority of intracellular Zn2+ following exposures to ZnSO4 was found in other larger vesicles, with less than 10% in endosomes and lysosomes. In conclusion, together, our observations indicate that low but critical levels of intracellular Zn2+ have to be reached, concentrated specifically in endosomes and lysosomes, for toxicity to occur, and point to the focal dissolution of the NPs in the cellular environment and the accumulation of the ions specifically in endosomes and lysosomes as the processes underlying the potent toxicity of airborne ZnO NPs.« less

  14. Calibration of hyperelastic material properties of the human lumbar intervertebral disc under fast dynamic compressive loads.

    PubMed

    Wagnac, Eric; Arnoux, Pierre-Jean; Garo, Anaïs; El-Rich, Marwan; Aubin, Carl-Eric

    2011-10-01

    Under fast dynamic loading conditions (e.g. high-energy impact), the load rate dependency of the intervertebral disc (IVD) material properties may play a crucial role in the biomechanics of spinal trauma. However, most finite element models (FEM) of dynamic spinal trauma uses material properties derived from quasi-static experiments, thus neglecting this load rate dependency. The aim of this study was to identify hyperelastic material properties that ensure a more biofidelic simulation of the IVD under a fast dynamic compressive load. A hyperelastic material law based on a first-order Mooney-Rivlin formulation was implemented in a detailed FEM of a L2-L3 functional spinal unit (FSU) to represent the mechanical behavior of the IVD. Bony structures were modeled using an elasto-plastic Johnson-Cook material law that simulates bone fracture while ligaments were governed by a viscoelastic material law. To mimic experimental studies performed in fast dynamic compression, a compressive loading velocity of 1 m/s was applied to the superior half of L2, while the inferior half of L3 was fixed. An exploratory technique was used to simulate dynamic compression of the FSU using 34 sets of hyperelastic material constants randomly selected using an optimal Latin hypercube algorithm and a set of material constants derived from quasi-static experiments. Selection or rejection of the sets of material constants was based on compressive stiffness and failure parameters criteria measured experimentally. The two simulations performed with calibrated hyperelastic constants resulted in nonlinear load-displacement curves with compressive stiffness (7335 and 7079 N/mm), load (12,488 and 12,473 N), displacement (1.95 and 2.09 mm) and energy at failure (13.5 and 14.7 J) in agreement with experimental results (6551 ± 2017 N/mm, 12,411 ± 829 N, 2.1 ± 0.2 mm and 13.0 ± 1.5 J respectively). The fracture pattern and location also agreed with experimental results. The simulation performed with

  15. Analysis of the Ultra-fast Switching Dynamics in a Hybrid MOSFET/Driver

    SciTech Connect

    Tang, T.; Burkhart, C.; /SLAC

    2011-08-17

    The turn-on dynamics of a power MOSFET during ultra-fast, {approx} ns, switching are discussed in this paper. The testing was performed using a custom hybrid MOSFET/Driver module, which was fabricated by directly assembling die-form components, power MOSFET and drivers, on a printed circuit board. By using die-form components, the hybrid approach substantially reduces parasitic inductance, which facilitates ultra-fast switching. The measured turn on time of the hybrid module with a resistive load is 1.2 ns with an applied voltage of 1000 V and drain current of 33 A. Detailed analysis of the switching waveforms reveals that switching behavior must be interpreted differently in the ultra-fast regime. For example, the gate threshold voltage to turn on the device is observed to increase as the switching time decreases. Further analysis and simulation of MOSFET switching behavior shows that the minimum turn on time scales with the product of the drain-source on resistance and drain-source capacitance, R{sub DS(on)}C{sub OSS}. This information will be useful in power MOSFET selection and gate driver design for ultra-fast switching applications.

  16. Dynamical programming based turbulence velocimetry for fast visible imaging of tokamak plasma

    NASA Astrophysics Data System (ADS)

    Banerjee, Santanu; Zushi, H.; Nishino, N.; Mishra, K.; Onchi, T.; Kuzmin, A.; Nagashima, Y.; Hanada, K.; Nakamura, K.; Idei, H.; Hasegawa, M.; Fujisawa, A.

    2015-03-01

    An orthogonal dynamic programming (ODP) based particle image velocimetry (PIV) technique is developed to measure the time resolved flow field of the fluctuating structures at the plasma edge and scrape off layer (SOL) of tokamaks. This non-intrusive technique can provide two dimensional velocity fields at high spatial and temporal resolution from a fast framing image sequence and hence can provide better insights into plasma flow as compared to conventional probe measurements. Applicability of the technique is tested with simulated image pairs. Finally, it is applied to tangential fast visible images of QUEST plasma to estimate the SOL flow in inboard poloidal null-natural divertor configuration. This technique is also applied to investigate the intricate features of the core of the run-away dominated phase following the injection of a large amount of neutrals in the target Ohmic plasma. Development of the ODP-PIV code and its applicability on actual plasma images is reported.

  17. BEAM DYNAMICS ANALYSIS FOR THE ULTRA-FAST KICKER IN CIRCULAR COOLER RING OF JLEIC

    SciTech Connect

    Huang, Yulu; Wang, Haipeng; Rimmer, Robert A.; Wang, Shaoheng

    2016-05-01

    An ultra-fast kicker system consisting of four quarter wavelength resonator based deflecting cavities was developed that simultaneously resonates at 10 subharmonic modes of the 476.3MHz bunch repetition frequency. Thus every 10th bunch in the bunch train will experience a transverse kick while all the other bunches are undisturbed. This fast kicker is being developed for the Energy Recovery Linac (ERL) based electron Circular Cooler Ring (CCR) in the proposed Jefferson Lab Electron Ion Collider (JLEIC, previously MEIC). The electron bunches can be reused 10-30 turns thus the beam current in the ERL can be reduced to 1/10 - 1/30 (150mA - 50mA) of the cooling bunch current (1.5A). In this paper, several methods to synthesize such a kicker waveform and the comparison made by the beam dynamics tracking in Elegant will be discussed.

  18. Intracellular carbonic anhydrase activity sensitizes cancer cell pH signaling to dynamic changes in CO2 partial pressure.

    PubMed

    Hulikova, Alzbeta; Aveyard, Nicholas; Harris, Adrian L; Vaughan-Jones, Richard D; Swietach, Pawel

    2014-09-12

    Carbonic anhydrase (CA) enzymes catalyze the chemical equilibration among CO2, HCO3(-) and H(+). Intracellular CA (CAi) isoforms are present in certain types of cancer, and growing evidence suggests that low levels correlate with disease severity. However, their physiological role remains unclear. Cancer cell CAi activity, measured as cytoplasmic CO2 hydration rate (kf), ranged from high in colorectal HCT116 (∼2 s(-1)), bladder RT112 and colorectal HT29, moderate in fibrosarcoma HT1080 to negligible (i.e. spontaneous kf = 0.18 s(-1)) in cervical HeLa and breast MDA-MB-468 cells. CAi activity in cells correlated with CAII immunoreactivity and enzymatic activity in membrane-free lysates, suggesting that soluble CAII is an important intracellular isoform. CAi catalysis was not obligatory for supporting acid extrusion by H(+) efflux or HCO3(-) influx, nor for maintaining intracellular pH (pHi) uniformity. However, in the absence of CAi activity, acid loading from a highly alkaline pHi was rate-limited by HCO3(-) supply from spontaneous CO2 hydration. In solid tumors, time-dependence of blood flow can result in fluctuations of CO2 partial pressure (pCO2) that disturb cytoplasmic CO2-HCO3(-)-H(+) equilibrium. In cancer cells with high CAi activity, extracellular pCO2 fluctuations evoked faster and larger pHi oscillations. Functionally, these resulted in larger pH-dependent intracellular [Ca(2+)] oscillations and stronger inhibition of the mTORC1 pathway reported by S6 kinase phosphorylation. In contrast, the pHi of cells with low CAi activity was less responsive to pCO2 fluctuations. Such low pass filtering would "buffer" cancer cell pHi from non-steady-state extracellular pCO2. Thus, CAi activity determines the coupling between pCO2 (a function of tumor perfusion) and pHi (a potent modulator of cancer cell physiology).

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

    PubMed

    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.

  20. Effects of fatigue and reduced intracellular pH on segment dynamics in 'isometric' relaxation of frog muscle fibres.

    PubMed Central

    Curtin, N A; Edman, K A

    1989-01-01

    1. Longitudinal movements of marked segments of single fibres from the anterior tibialis muscle were recorded during tetanus and relaxation under isometric (fixed-end) conditions. 2. During relaxation, shortening and lengthening of different segments occurred simultaneously, starting at about the same time as the end of the linear fall of force (shoulder on the force record). 3. Variations in intracellular pH, measured with pH-sensitive microelectrodes, along the length of fibres were not statistically significant, and are unlikely to be responsible for the non-uniform behaviour of different segments. 4. As expected from earlier studies, both fatigue (produced by increasing tetanus duration or decreasing the time between tetani) and intracellular acidification (produced by raised extracellular CO2), reduced the tetanus force and prolonged the linear phase of force decline in relaxation. Each treatment delayed the start and markedly reduced the amount of segment movement in relaxation. 5. Fatigue and intracellular acidification have a smaller effect on force during stretching than on force produced under isometric conditions. This may contribute to making the segments behave in a more uniform way during relaxation under these conditions. 6. Changes in the Ca2+ uptake mechanisms are also discussed as possible causes for the changes in segment behaviour in relaxation. PMID:2600846

  1. Fast methods incorporating direct elliptic solvers for nonlinear applications in fluid dynamics

    NASA Technical Reports Server (NTRS)

    Martin, E. D.

    1977-01-01

    Semidirect methods are discussed, their present role, as well as some developments for their application in computational fluid dynamics. A semidirect method is a computational scheme that uses a fast, direct, elliptic solver as the driving algorithm for the iterative solution of finite difference equations. Specific subtopics include: (1) direct Cauchy Riemann solvers for first order elliptic equations; (2) application of the semidirect method to the mixed elliptic hyperbolic problem of steady, inviscid transonic flow; and (3) the treatment of interior conditions, such as those on an airfoil or wing, in semidirect methods.

  2. Fast optical cooling of a nanomechanical cantilever by a dynamical Stark-shift gate.

    PubMed

    Yan, Leilei; Zhang, Jian-Qi; Zhang, Shuo; Feng, Mang

    2015-10-12

    The efficient cooling of nanomechanical resonators is essential to exploration of quantum properties of the macroscopic or mesoscopic systems. We propose such a laser-cooling scheme for a nanomechanical cantilever, which works even for the low-frequency mechanical mode and under weak cooling lasers. The cantilever is coupled by a diamond nitrogen-vacancy center under a strong magnetic field gradient and the cooling is assisted by a dynamical Stark-shift gate. Our scheme can effectively enhance the desired cooling efficiency by avoiding the off-resonant and undesired carrier transitions, and thereby cool the cantilever down to the vicinity of the vibrational ground state in a fast fashion.

  3. Fast optical cooling of a nanomechanical cantilever by a dynamical Stark-shift gate

    NASA Astrophysics Data System (ADS)

    Yan, Leilei; Zhang, Jian-Qi; Zhang, Shuo; Feng, Mang

    2015-10-01

    The efficient cooling of nanomechanical resonators is essential to exploration of quantum properties of the macroscopic or mesoscopic systems. We propose such a laser-cooling scheme for a nanomechanical cantilever, which works even for the low-frequency mechanical mode and under weak cooling lasers. The cantilever is coupled by a diamond nitrogen-vacancy center under a strong magnetic field gradient and the cooling is assisted by a dynamical Stark-shift gate. Our scheme can effectively enhance the desired cooling efficiency by avoiding the off-resonant and undesired carrier transitions, and thereby cool the cantilever down to the vicinity of the vibrational ground state in a fast fashion.

  4. Ultra-fast dynamic compression technique to study kinetics of phase transformations in Bismuth

    SciTech Connect

    Smith, R F; Kane, J O; Eggert, J H; Saculla, M D; Jankowski, A F; Bastea, M; Hicks, D G; Collins, G W

    2007-12-28

    Pre-heated Bi was ramp compressed within 30 ns to a peak stress of {approx}11 GPa to explore structural phase transformation kinetics under dynamic loading conditions. Under these ultra-fast compression time-scales the equilibrium Bi I-II phase boundary is overpressurized by {Delta}P {approx} 0.8 GPa. {Delta}P is observed to increase logarithmically with strain rate, {var_epsilon}, above 10{sup 6} s{sup -1}. Estimates from a kinetics model predict that the Bi I phase is fully transformed within 3 ns.

  5. A surface ice module for wind turbine dynamic response simulation using FAST

    SciTech Connect

    Yu, Bingbin; Karr, Dale G.; Song, Huimin; Sirnivas, Senu

    2016-06-03

    It is a fact that developing offshore wind energy has become more and more serious worldwide in recent years. Many of the promising offshore wind farm locations are in cold regions that may have ice cover during wintertime. The challenge of possible ice loads on offshore wind turbines raises the demand of modeling capacity of dynamic wind turbine response under the joint action of ice, wind, wave, and current. The simulation software FAST is an open source computer-aided engineering (CAE) package maintained by the National Renewable Energy Laboratory. In this paper, a new module of FAST for assessing the dynamic response of offshore wind turbines subjected to ice forcing is presented. In the ice module, several models are presented which involve both prescribed forcing and coupled response. For conditions in which the ice forcing is essentially decoupled from the structural response, ice forces are established from existing models for brittle and ductile ice failure. For conditions in which the ice failure and the structural response are coupled, such as lock-in conditions, a rate-dependent ice model is described, which is developed in conjunction with a new modularization framework for FAST. In this paper, analytical ice mechanics models are presented that incorporate ice floe forcing, deformation, and failure. For lower speeds, forces slowly build until the ice strength is reached and ice fails resulting in a quasi-static condition. For intermediate speeds, the ice failure can be coupled with the structural response and resulting in coinciding periods of the ice failure and the structural response. A third regime occurs at high speeds of encounter in which brittle fracturing of the ice feature occurs in a random pattern, which results in a random vibration excitation of the structure. An example wind turbine response is simulated under ice loading of each of the presented models. This module adds to FAST the capabilities for analyzing the response of wind

  6. The reversibility error method (REM): a new, dynamical fast indicator for planetary dynamics

    NASA Astrophysics Data System (ADS)

    Panichi, Federico; Goździewski, Krzyszof; Turchetti, Giorgio

    2017-02-01

    We describe the reversibility error method (REM) and its applications to planetary dynamics. REM is based on the time-reversibility analysis of the phase-space trajectories of conservative Hamiltonian systems. The round-off errors break the time reversibility and the displacement from the initial condition, occurring when we integrate it forward and backward for the same time interval, is related to the dynamical character of the trajectory. If the motion is chaotic, in the sense of non-zero maximal Lyapunov characteristic exponent (mLCE), then REM increases exponentially with time, as exp λt, while when the motion is regular (quasi-periodic), then REM increases as a power law in time, as tα, where α and λ are real coefficients. We compare the REM with a variant of mLCE, the mean exponential growth factor of nearby orbits. The test set includes the restricted three-body problem and five resonant planetary systems: HD 37124, Kepler-60, Kepler-36, Kepler-29 and Kepler-26. We found a very good agreement between the outcomes of these algorithms. Moreover, the numerical implementation of REM is astonishing simple, and is based on solid theoretical background. The REM requires only a symplectic and time-reversible (symmetric) integrator of the equations of motion. This method is also CPU efficient. It may be particularly useful for the dynamical analysis of multiple planetary systems in the Kepler sample, characterized by low-eccentricity orbits and relatively weak mutual interactions. As an interesting side result, we found a possible stable chaos occurrence in the Kepler-29 planetary system.

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

    PubMed

    Gu, Taoli; Wei, Bingqing

    2015-07-21

    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.

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

    SciTech Connect

    Acharya, Naresh; Baone, Chaitanya; Veda, Santosh; Dai, Jing; Chaudhuri, Nilanjan; Leonardi, Bruno; Sanches-Gasca, Juan; Diao, Ruisheng; Wu, Di; Huang, Zhenyu; Zhang, Yu; Jin, Shuangshuang; Zheng, Bin; Chen, Yousu

    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

  9. Fast Dynamical Coupling Enhances Frequency Adaptation of Oscillators for Robotic Locomotion Control

    PubMed Central

    Nachstedt, Timo; Tetzlaff, Christian; Manoonpong, Poramate

    2017-01-01

    Rhythmic neural signals serve as basis of many brain processes, in particular of locomotion control and generation of rhythmic movements. It has been found that specific neural circuits, named central pattern generators (CPGs), are able to autonomously produce such rhythmic activities. In order to tune, shape and coordinate the produced rhythmic activity, CPGs require sensory feedback, i.e., external signals. Nonlinear oscillators are a standard model of CPGs and are used in various robotic applications. A special class of nonlinear oscillators are adaptive frequency oscillators (AFOs). AFOs are able to adapt their frequency toward the frequency of an external periodic signal and to keep this learned frequency once the external signal vanishes. AFOs have been successfully used, for instance, for resonant tuning of robotic locomotion control. However, the choice of parameters for a standard AFO is characterized by a trade-off between the speed of the adaptation and its precision and, additionally, is strongly dependent on the range of frequencies the AFO is confronted with. As a result, AFOs are typically tuned such that they require a comparably long time for their adaptation. To overcome the problem, here, we improve the standard AFO by introducing a novel adaptation mechanism based on dynamical coupling strengths. The dynamical adaptation mechanism enhances both the speed and precision of the frequency adaptation. In contrast to standard AFOs, in this system, the interplay of dynamics on short and long time scales enables fast as well as precise adaptation of the oscillator for a wide range of frequencies. Amongst others, a very natural implementation of this mechanism is in terms of neural networks. The proposed system enables robotic applications which require fast retuning of locomotion control in order to react to environmental changes or conditions. PMID:28377710

  10. Fast dynamics of type I and grassy ELMs in JT-60U

    NASA Astrophysics Data System (ADS)

    Kojima, A.; Oyama, N.; Sakamoto, Y.; Kamada, Y.; Urano, H.; Kamiya, K.; Fujita, T.; Kubo, H.; Aiba, N.; JT-60 Team

    2009-11-01

    In order to understand the physics of the ELM trigger and determine the ELM size, the fast ELM dynamics of type I and grassy ELMs have been studied in JT-60U, using new fast diagnostics with high spatial and temporal resolutions such as a lithium beam probe (Δt ~ 0.5 ms) and a charge exchange recombination spectroscopy (Δt ~ 2.5 ms), which can measure the electron density and the ion temperature, respectively. The evolution of the ion pressure profile in the pedestal region has been evaluated for the first time by detailed edge profile measurements. Then, the dynamics of the density, the ion temperature and the ion pressure in the ELM cycle has been investigated. The co-rotating plasmas are compared with the counter (ctr)-rotating plasmas for the understanding of the toroidal rotation effects. Type I ELMs observed in co-rotating plasmas exhibit a larger and wider ELM affected area (Δnped/nped ~ 30%, radial extent >15 cm) than ctr-rotating plasmas (Δnped/nped ~ 20%, radial extent ~10 cm). Just before a type I ELM crash, the pedestal ion pressure and its maximum gradient in co-rotating plasmas are 20% and 12% higher than those in ctr-rotating plasmas, respectively. It is found that the radial extent of the ion pressure gradient at the pedestal region in co-rotating plasmas is 14% wider than that in ctr-rotating plasmas. The experimental results suggest that the ELM size is connected with the structure of the plasma pressure in the whole pedestal region. As for the dynamics of grassy ELMs, the collapse of density pedestal is smaller (<20%) and narrower (~5 cm) than those of type I ELMs, as observed in the collapse of the electron temperature pedestal. Thus, it is confirmed that both conductive and convective losses due to grassy ELMs are small.

  11. A surface ice module for wind turbine dynamic response simulation using FAST

    DOE PAGES

    Yu, Bingbin; Karr, Dale G.; Song, Huimin; ...

    2016-06-03

    It is a fact that developing offshore wind energy has become more and more serious worldwide in recent years. Many of the promising offshore wind farm locations are in cold regions that may have ice cover during wintertime. The challenge of possible ice loads on offshore wind turbines raises the demand of modeling capacity of dynamic wind turbine response under the joint action of ice, wind, wave, and current. The simulation software FAST is an open source computer-aided engineering (CAE) package maintained by the National Renewable Energy Laboratory. In this paper, a new module of FAST for assessing the dynamicmore » response of offshore wind turbines subjected to ice forcing is presented. In the ice module, several models are presented which involve both prescribed forcing and coupled response. For conditions in which the ice forcing is essentially decoupled from the structural response, ice forces are established from existing models for brittle and ductile ice failure. For conditions in which the ice failure and the structural response are coupled, such as lock-in conditions, a rate-dependent ice model is described, which is developed in conjunction with a new modularization framework for FAST. In this paper, analytical ice mechanics models are presented that incorporate ice floe forcing, deformation, and failure. For lower speeds, forces slowly build until the ice strength is reached and ice fails resulting in a quasi-static condition. For intermediate speeds, the ice failure can be coupled with the structural response and resulting in coinciding periods of the ice failure and the structural response. A third regime occurs at high speeds of encounter in which brittle fracturing of the ice feature occurs in a random pattern, which results in a random vibration excitation of the structure. An example wind turbine response is simulated under ice loading of each of the presented models. This module adds to FAST the capabilities for analyzing the response of wind

  12. Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiology at the single-cell level

    PubMed Central

    Yu, Qianru; Heikal, Ahmed A.

    2009-01-01

    Reduced nicotinamide adenine dinucleotide, NADH, is a major electron donor in the oxidative phosphorylation and glycolytic pathways in cells. As a result, there has been recent resurgence in employing intrinsic NADH fluorescence as a natural probe for a range of cellular processes that include apoptosis, cancer pathology, and enzyme kinetics. Here, we report on two-photon fluorescence lifetime and polarization imaging of intrinsic NADH in breast cancer (Hs578T) and normal (Hs578Bst) cells for quantitative analysis of the concentration and conformation (i.e., free-to-enzyme-bound ratios) of this coenzyme. Two-photon fluorescence lifetime imaging of intracellular NADH indicates sensitivity to both cell pathology and inhibition of the respiratory chain activities using potassium cyanide (KCN). Using a newly developed noninvasive assay, we estimate the average NADH concentration in cancer cells (168 ± 49 μM) to be ~ 1.8 fold higher than in breast normal cells (99 ± 37 μM). Such analyses indicate changes in energy metabolism and redox reactions in normal breast cells upon inhibition of the respiratory chain activity using KCN. In addition, time-resolved associated anisotropy of cellular autofluorescence indicates population fractions of free (0.18 ± 0.08) and enzyme-bound (0.82 ± 0.08) conformations of intracellular NADH in normal breast cells. These fractions are statistically different from those in breast cancer cells (free: 0.25 ± 0.08; bound: 0.75 ± 0.08). Comparative studies on the binding kinetics of NADH with mitochondrial malate dehydrogenase and lactate dehydrogenase in solution mimic our findings in living cells. These quantitative studies demonstrate the potential of intracellular NADH dynamics (rather than intensity) imaging for probing mitochondrial anomalies associated with neurodegenerative diseases, cancer, diabetes, and aging. Our approach is also applicable to other metabolic and signaling pathways in living cells, without the need for cell

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

    SciTech Connect

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

    2014-12-21

    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.

  14. Fast-scan cyclic voltammetry analysis of dynamic serotonin reponses to acute escitalopram.

    PubMed

    Wood, Kevin M; Hashemi, Parastoo

    2013-05-15

    The treatment of depression with selective serotonin reuptake inhibitors, SSRIs, is important to study on a neurochemical level because of the therapeutic variability experienced by many depressed patients. We employed the rapid temporal capabilities of fast scan cyclic voltammetry at carbon fiber microelectrodes to study the effects of a popular SSRI, escitalopram (ESCIT), marketed as Lexapro, on serotonin in mice. We report novel, dynamic serotonin behavior after acute ESCIT doses, characterized by a rapid increase in stimulated serotonin release and a gradual rise in serotonin clearance over 120 min. Dynamic changes after acute SSRI doses may be clinically relevant to the pathology of increased depression or suicidality after onset of antidepressant treatment. Due to the short-term variability of serotonin responses after acute ESCIT, we outline difficulties in creating dose response curves and we suggest effective means to visualize dynamic serotonin changes after SSRIs. Correlating chemical serotonin patterns to clinical findings will allow a finer understanding of SSRI mechanisms, ultimately providing a platform for reducing therapeutic variability.

  15. Fast space-filling molecular graphics using dynamic partitioning among parallel processors.

    PubMed

    Gertner, B J; Whitnell, R M; Wilson, K R

    1991-09-01

    We present a novel algorithm for the efficient generation of high-quality space-filling molecular graphics that is particularly appropriate for the creation of the large number of images needed in the animation of molecular dynamics. Each atom of the molecule is represented by a sphere of an appropriate radius, and the image of the sphere is constructed pixel-by-pixel using a generalization of the lighting model proposed by Porter (Comp. Graphics 1978, 12, 282). The edges of the spheres are antialiased, and intersections between spheres are handled through a simple blending algorithm that provides very smooth edges. We have implemented this algorithm on a multiprocessor computer using a procedure that dynamically repartitions the effort among the processors based on the CPU time used by each processor to create the previous image. This dynamic reallocation among processors automatically maximizes efficiency in the face of both the changing nature of the image from frame to frame and the shifting demands of the other programs running simultaneously on the same processors. We present data showing the efficiency of this multiprocessing algorithm as the number of processors is increased. The combination of the graphics and multiprocessor algorithms allows the fast generation of many high-quality images.

  16. Pulsed holographic microscopy as a measurement method of dynamic fracture toughness for fast propagating cracks

    NASA Astrophysics Data System (ADS)

    Suzuki, Shinichi; Homma, Hiroomi; Kusaka, Riichiro

    A METHOD OF pulsed holographic microscopy is applied to take instantaneous microscopic photographs of the neighborhoods of crack tips propagating through PMMA or through AISI 4340 steel specimens at a speed of several hundred meters per second. The cracks are in the opening mode. A fast propagating crack is recorded as a hologram at an instant during its propagation. A microscopic photograph of the crack is taken with a conventional microscope to magnify the reconstructed image from the hologram. From the microscopic photograph, crack opening displacement (COD) is measured along the crack in the vicinity of the crack tip. The COD is of the order often to one hundred microns, and in proportion to the square root of the distance from the crack tip. The dynamic fracture toughness KID is obtained using the formula for COD in the singular stress field of a fast propagating crack. Simultaneous KID measurement both through pulsed holographic microscopy and through the caustic method is furthermore carried out with PMMA specimens. The values of KID obtained through pulsed holographic microscopy are in agreement with those through the caustic method. Microcracks accompanied by a main crack are also photographed with the method of pulsed holographic microscopy.

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Metal hydrides reactors with improved dynamic characteristics for a fast cycling hydrogen compressor

    NASA Astrophysics Data System (ADS)

    Popeneciu, G.; Coldea, I.; Lupu, D.; Misan, I.; Ardelean, O.

    2009-08-01

    This paper presents an investigation of coupled heat and mass transfer process in metal hydrides hydrogen storage reactors. Hydrogen storage and compression performance of our designed and developed reactors are studied by varying the operating parameters and analyzing the effects of metal hydride bed parameters. The metal alloy selected to characterize the cycling behaviour of reactors is LaNi5, material synthesized and characterized by us in the range 20-80°C. Four types of metal hydride reactors were tested with the aim to provide a fast hydrogen absorption-desorption cycle, able to be thermally cycled at rapid rates. Some new technical solutions have been studied to make a step forward in reducing the duration of the reactors cycle, which combines the effective increase of the thermal conductivity and good permeability to hydrogen gas. Dynamic characteristic of developed fast metal hydride reactors is improved using our novel mixture metal hydride-CA conductive additive due to the increased effective thermal conductivity of the alloy bed. The advanced hydride bed design with high heat transfer capabilities can be thermally cycled at a rapid rate, under 120 seconds, in order to process high hydrogen flow rates.

  19. Distributed measurement of dynamic strain based on multi-slope assisted fast BOTDA.

    PubMed

    Ba, Dexin; Wang, Benzhang; Zhou, Dengwang; Yin, Mingjing; Dong, Yongkang; Li, Hui; Lu, Zhiwei; Fan, Zhigang

    2016-05-02

    We propose and demonstrate a dynamic Brillouin optical fiber sensing based on the multi-slope assisted fast Brillouin optical time-domain analysis (F-BOTDA), which enables the measurement of a large strain with real-time data processing. The multi-slope assisted F-BOTDA is realized based on the double-slope demodulation and frequency-agile modulation, which significantly increases the measurement range compared with the single- or double- slope assisted F-BOTDA, while maintaining the advantage of fast data processing and being suitable for real-time on-line monitoring. A maximum strain variation up to 5000με is measured in a 32-m fiber with a spatial resolution of ~1m and a sampling rate of 1kHz. The frequency of the strain is 12.8Hz, which is limited by the rotation rate of the motor used to load the force on the fiber. Furthermore, the influence of the frequency difference between two adjacent probe tones on the measurement error is studied theoretically and experimentally for optimization. For a Brillouin gain spectrum with a 78-MHz width, the optimum frequency difference is ~40MHz. The measurement error of Brillouin frequency shift is less than 3MHz over the whole measurement range (241MHz).

  20. Fast and accurate quantum molecular dynamics of dense plasmas across temperature regimes

    SciTech Connect

    Sjostrom, Travis; Daligault, Jerome

    2014-10-10

    Here, we develop and implement a new quantum molecular dynamics approximation that allows fast and accurate simulations of dense plasmas from cold to hot conditions. The method is based on a carefully designed orbital-free implementation of density functional theory. The results for hydrogen and aluminum are in very good agreement with Kohn-Sham (orbital-based) density functional theory and path integral Monte Carlo calculations for microscopic features such as the electron density as well as the equation of state. The present approach does not scale with temperature and hence extends to higher temperatures than is accessible in the Kohn-Sham method and lower temperatures than is accessible by path integral Monte Carlo calculations, while being significantly less computationally expensive than either of those two methods.

  1. Fast and accurate quantum molecular dynamics of dense plasmas across temperature regimes

    DOE PAGES

    Sjostrom, Travis; Daligault, Jerome

    2014-10-10

    Here, we develop and implement a new quantum molecular dynamics approximation that allows fast and accurate simulations of dense plasmas from cold to hot conditions. The method is based on a carefully designed orbital-free implementation of density functional theory. The results for hydrogen and aluminum are in very good agreement with Kohn-Sham (orbital-based) density functional theory and path integral Monte Carlo calculations for microscopic features such as the electron density as well as the equation of state. The present approach does not scale with temperature and hence extends to higher temperatures than is accessible in the Kohn-Sham method and lowermore » temperatures than is accessible by path integral Monte Carlo calculations, while being significantly less computationally expensive than either of those two methods.« less

  2. Fast optical cooling of a nanomechanical cantilever by a dynamical Stark-shift gate

    PubMed Central

    Yan, Leilei; Zhang, Jian-Qi; Zhang, Shuo; Feng, Mang

    2015-01-01

    The efficient cooling of nanomechanical resonators is essential to exploration of quantum properties of the macroscopic or mesoscopic systems. We propose such a laser-cooling scheme for a nanomechanical cantilever, which works even for the low-frequency mechanical mode and under weak cooling lasers. The cantilever is coupled by a diamond nitrogen-vacancy center under a strong magnetic field gradient and the cooling is assisted by a dynamical Stark-shift gate. Our scheme can effectively enhance the desired cooling efficiency by avoiding the off-resonant and undesired carrier transitions, and thereby cool the cantilever down to the vicinity of the vibrational ground state in a fast fashion. PMID:26455901

  3. FAST: A multi-processed environment for visualization of computational fluid dynamics

    NASA Technical Reports Server (NTRS)

    Bancroft, Gordon V.; Merritt, Fergus J.; Plessel, Todd C.; Kelaita, Paul G.; Mccabe, R. Kevin

    1991-01-01

    Three-dimensional, unsteady, multi-zoned fluid dynamics simulations over full scale aircraft are typical of the problems being investigated at NASA Ames' Numerical Aerodynamic Simulation (NAS) facility on CRAY2 and CRAY-YMP supercomputers. With multiple processor workstations available in the 10-30 Mflop range, we feel that these new developments in scientific computing warrant a new approach to the design and implementation of analysis tools. These larger, more complex problems create a need for new visualization techniques not possible with the existing software or systems available as of this writing. The visualization techniques will change as the supercomputing environment, and hence the scientific methods employed, evolves even further. The Flow Analysis Software Toolkit (FAST), an implementation of a software system for fluid mechanics analysis, is discussed.

  4. Extending the zero-derivative principle for slow-fast dynamical systems

    NASA Astrophysics Data System (ADS)

    Benoît, Eric; Brøns, Morten; Desroches, Mathieu; Krupa, Martin

    2015-10-01

    Slow-fast systems often possess slow manifolds, that is invariant or locally invariant sub-manifolds on which the dynamics evolves on the slow time scale. For systems with explicit timescale separation, the existence of slow manifolds is due to Fenichel theory, and asymptotic expansions of such manifolds are easily obtained. In this paper, we discuss methods of approximating slow manifolds using the so-called zero-derivative principle. We demonstrate several test functions that work for systems with explicit time scale separation including ones that can be generalized to systems without explicit timescale separation. We also discuss the possible spurious solutions, known as ghosts, as well as treat the Templator system as an example.

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

    PubMed

    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.

  6. Intracellular kinetics of ATX-S10·Na(II) and its correlation with photochemical reaction dynamics during a pulsed photosensitization process: effect of pulse repetition rate

    NASA Astrophysics Data System (ADS)

    Kawauchi, Satoko; Sato, Shunichi; Morimoto, Yuji; Kikuchi, Makoto

    2006-01-01

    Although photodynamic therapy with pulsed light excitation has interesting characteristics, its photosensitization mechanism has not been fully elucidated. In this study, we showed that the intracellular kinetics of ATX-S10.Na(II), a lysosomal sensitizer, was closely related to photochemical reaction dynamics during photodynamic treatment of A549 cells with nanosecond pulsed light. Fluorescence microscopy revealed that at high frequencies of 10 and 30 Hz the sensitizer initially localized mainly in lysosomes but that it started to be redistributed to the cytosol in certain ranges of radiant exposures. These ranges were found to coincide with a regime of fluorescence degradation with limited oxygen consumption. On the other hand, at 5 Hz, there was no such a discontinuous behavior in the sensitizer redistribution characteristics throughout the period of irradiation; this was consistent with the fact that no reaction switching was observed. Two possible reasons for the appearance of the regime with limited oxygen consumption are discussed: participation of an oxygen-independent reaction and change in the microenvironment for the sensitizer caused by lysosomal photodamage. The pulse frequency-dependent intracellular kinetics of the sensitizer also explains our previous results showing higher cytotoxicity at 5 Hz than at 10 and 30 Hz.

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

    SciTech Connect

    Dyson, Brian; Chang, N.-B. . E-mail: nchang@even.tamuk.edu

    2005-07-01

    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.

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

    PubMed

    Dyson, Brian; Chang, Ni-Bin

    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. 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.

  9. SPH modeling of adhesion in fast dynamics: Application to the Cold Spray process

    NASA Astrophysics Data System (ADS)

    Profizi, Paul; Combescure, Alain; Ogawa, Kahuziro

    2016-04-01

    The objective of this paper is to show, in a specific case, the importance of modeling adhesive forces when simulating the bouncing of very small particles impacting a substrate at high speed. The implementation of this model into a fast-dynamics SPH code is described. Taking the example of an impacted elastic cylinder, we show that the adhesive forces, which are surface forces, play a significant role only if the particles are sufficiently small. The effect of the choice of the type of interaction law in the cohesive zone is studied and some conclusions on the relevance of the modeling of the adhesive forces for fast-dynamics impacts are drawn. Then, the adhesion model is used to simulate the Cold Spray process. An aluminum particle is projected against a substrate made of the same material at a velocity ranging from 200 to 1000 m ṡs-1. We study the effects of the various modeling assumptions on the final result: bouncing or sticking. Increasingly complex models are considered. At a 200 m ṡs-1 impact velocity, elastic behavior is assumed, the substrate being simply supported at its base and supplied with absorbing boundaries. The same absorbing boundaries are also used for all the other simulations. Then, plasticity is introduced and the impact velocity is increased up to 1000 m ṡs-1. At the highest velocities, the resulting strains are very significant. The calculations show that if the adhesion model is appropriately chosen, it is possible to reproduce the experimental observations: the particles stick to the substrate in a range of impact velocities surrounded by two velocity ranges in which the particles bounce.

  10. Molecular dynamics-based selectivity for Fast-Field-Cycling relaxometry by Overhauser and solid effect dynamic nuclear polarization

    NASA Astrophysics Data System (ADS)

    Neudert, Oliver; Mattea, Carlos; Stapf, Siegfried

    2017-03-01

    In the last decade nuclear spin hyperpolarization methods, especially Dynamic Nuclear Polarization (DNP), have provided unprecedented possibilities for various NMR techniques by increasing the sensitivity by several orders of magnitude. Recently, in-situ DNP-enhanced Fast Field Cycling (FFC) relaxometry was shown to provide appreciable NMR signal enhancements in liquids and viscous systems. In this work, a measurement protocol for DNP-enhanced NMR studies is introduced which enables the selective detection of nuclear spin hyperpolarized by either Overhauser effect or solid effect DNP. Based on field-cycled DNP and relaxation studies it is shown that these methods allow for the independent measurement of polymer and solvent nuclear spins in a concentrated solution of high molecular weight polybutadiene in benzene doped with α,γ-bisdiphenylene-β-phenylallyl radical. Appreciable NMR signal enhancements of about 10-fold were obtained for both constituents. Moreover, qualitative information about the dynamics of the radical and solvent was obtained. Selective DNP-enhanced FFC relaxometry is applied for the measurement of the 1H nuclear magnetic relaxation dispersion of both constituents with improved precision. The introduced method is expected to greatly facilitate NMR studies of complex systems with multiple overlapping signal contributions that cannot be distinguished by standard methods.

  11. Molecular dynamics-based selectivity for Fast-Field-Cycling relaxometry by Overhauser and solid effect dynamic nuclear polarization.

    PubMed

    Neudert, Oliver; Mattea, Carlos; Stapf, Siegfried

    2017-03-01

    In the last decade nuclear spin hyperpolarization methods, especially Dynamic Nuclear Polarization (DNP), have provided unprecedented possibilities for various NMR techniques by increasing the sensitivity by several orders of magnitude. Recently, in-situ DNP-enhanced Fast Field Cycling (FFC) relaxometry was shown to provide appreciable NMR signal enhancements in liquids and viscous systems. In this work, a measurement protocol for DNP-enhanced NMR studies is introduced which enables the selective detection of nuclear spin hyperpolarized by either Overhauser effect or solid effect DNP. Based on field-cycled DNP and relaxation studies it is shown that these methods allow for the independent measurement of polymer and solvent nuclear spins in a concentrated solution of high molecular weight polybutadiene in benzene doped with α,γ-bisdiphenylene-β-phenylallyl radical. Appreciable NMR signal enhancements of about 10-fold were obtained for both constituents. Moreover, qualitative information about the dynamics of the radical and solvent was obtained. Selective DNP-enhanced FFC relaxometry is applied for the measurement of the (1)H nuclear magnetic relaxation dispersion of both constituents with improved precision. The introduced method is expected to greatly facilitate NMR studies of complex systems with multiple overlapping signal contributions that cannot be distinguished by standard methods.

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

    PubMed Central

    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

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

    PubMed

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

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

    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.

  15. Single-cell resolution of intracellular T cell Ca(2+) dynamics in response to frequency-based H2O2 stimulation.

    PubMed

    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 H2O2. 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, H2O2 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.

  16. An integrated dynamic model of ocean mining system and fast simulation of its longitudinal reciprocating motion

    NASA Astrophysics Data System (ADS)

    Dai, Yu; Liu, Shao-jun

    2013-04-01

    An integrated dynamic model of China's deep ocean mining system is developed and the fast simulation analysis of its longitudinal reciprocating motion operation processes is achieved. The seafloor tracked miner is built as a three-dimensional single-body model with six-degree-of-freedom. The track-terrain interaction is modeled by partitioning the track-terrain interface into a certain number of mesh elements with three mutually perpendicular forces, including the normal force, the longitudinal shear force and the lateral shear force, acting on the center point of each mesh element. The hydrodynamic force of the miner is considered and applied. By considering the operational safety and collection efficiency, two new mining paths for the miner on the seafloor are proposed, which can be simulated with the established single-body dynamic model of the miner. The pipeline subsystem is built as a three-dimensional multi-body discrete element model, which is divided into rigid elements linked by flexible connectors. The flexible connector without mass is represented by six spring-damper elements. The external hydrodynamic forces of the ocean current from the longitudinal and lateral directions are both considered and modeled based on the Morison formula and applied to the mass center of each corresponding discrete rigid element. The mining ship is simplified and represented by a general kinematic point, whose heave motion induced by the ocean waves and the longitudinal and lateral towing motions are considered and applied. By integrating the single-body dynamic model of the miner and the multi-body discrete element dynamic model of the pipeline, and defining the kinematic equations of the mining ship, the integrated dynamic model of the total deep ocean mining system is formed. The longitudinal reciprocating motion operation modes of the total mining system, which combine the active straight-line and turning motions of the miner and the ship, and the passive towed motions

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

    PubMed

    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.

  18. Fast and Quantitative T1ρ-weighted Dynamic Glucose Enhanced MRI

    PubMed Central

    Schuenke, Patrick; Paech, Daniel; Koehler, Christina; Windschuh, Johannes; Bachert, Peter; Ladd, Mark E.; Schlemmer, Heinz-Peter; Radbruch, Alexander; Zaiss, Moritz

    2017-01-01

    Common medical imaging techniques usually employ contrast agents that are chemically labeled, e.g. with radioisotopes in the case of PET, iodine in the case of CT or paramagnetic metals in the case of MRI to visualize the heterogeneity of the tumor microenvironment. Recently, it was shown that natural unlabeled D-glucose can be used as a nontoxic biodegradable contrast agent in Chemical Exchange sensitive Spin-Lock (CESL) magnetic resonance imaging (MRI) to detect the glucose uptake and potentially the metabolism of tumors. As an important step to fulfill the clinical needs for practicability, reproducibility and imaging speed we present here a robust and quantitative T1ρ-weighted technique for dynamic glucose enhanced MRI (DGE-MRI) with a temporal resolution of less than 7 seconds. Applied to a brain tumor patient, the new technique provided a distinct DGE contrast between tumor and healthy brain tissue and showed the detailed dynamics of the glucose enhancement after intravenous injection. Development of this fast and quantitative DGE-MRI technique allows for a more detailed analysis of DGE correlations in the future and potentially enables non-invasive diagnosis, staging and monitoring of tumor response to therapy. PMID:28169369

  19. Fast three-dimensional measurements for dynamic scenes with shiny surfaces

    NASA Astrophysics Data System (ADS)

    Feng, Shijie; Chen, Qian; Zuo, Chao; Asundi, Anand

    2017-01-01

    This paper presents a novel fringe projection technique for fast three-dimensional (3-D) shape measurements of moving highly reflective objects. By combining the standard three-step phase-shifting fringe patterns with a digital speckle image, dynamic 3-D reconstructions of shiny surfaces can be efficiently achieved with only four projected patterns. The phase measurement is performed by three-step phase-shifting algorithm as it uses the theoretical minimum number of fringe patterns for phase-shifting profilometry. To avoid the camera saturation, a dual-camera fringe projection system is built to measure shiny objects from two different directions. The erroneous phase obtained from a saturated pixel is corrected by the phase of its corresponding pixel in the other view which is free from the saturation problem. To achieve high measurement accuracy, the corresponding high light intensity areas in cameras are found by sub-pixel matches of the speckle pattern in either view. Benefited from the trifocal tensor constraint, the corresponding points in the two wrapped phase maps can be directly established, and thus, the difficulties in determining the correct fringe order for the discontinuous or isolated surfaces can be effectively bypassed. Experimental results indicate that the proposed method is able to successfully measure highly reflective surfaces for both stationary and dynamic scenes.

  20. Portable low-coherence interferometry for quantitatively imaging fast dynamics with extended field of view

    NASA Astrophysics Data System (ADS)

    Shaked, Natan T.; Girshovitz, Pinhas; Frenklach, Irena

    2014-06-01

    We present our recent advances in the development of compact, highly portable and inexpensive wide-field interferometric modules. By a smart design of the interferometric system, including the usage of low-coherence illumination sources and common-path off-axis geometry of the interferometers, spatial and temporal noise levels of the resulting quantitative thickness profile can be sub-nanometric, while processing the phase profile in real time. In addition, due to novel experimentally-implemented multiplexing methods, we can capture low-coherence off-axis interferograms with significantly extended field of view and in faster acquisition rates. Using these techniques, we quantitatively imaged rapid dynamics of live biological cells including sperm cells and unicellular microorganisms. Then, we demonstrated dynamic profiling during lithography processes of microscopic elements, with thicknesses that may vary from several nanometers to hundreds of microns. Finally, we present new algorithms for fast reconstruction (including digital phase unwrapping) of off-axis interferograms, which allow real-time processing in more than video rate on regular single-core computers.

  1. Energy efficient low power shared-memory Fast Fourier Transform (FFT) processor with dynamic voltage scaling

    NASA Astrophysics Data System (ADS)

    Fitrio, D.; Singh, J.; Stojcevski, A.

    2005-12-01

    Reduction of power dissipations in CMOS circuits needs to be addressed for portable battery devices. Selection of appropriate transistor library to minimise leakage current, implementation of low power design architectures, power management implementation, and the choice of chip packaging, all have impact on power dissipation and are important considerations in design and implementation of integrated circuits for low power applications. Energy-efficient architecture is highly desirable for battery operated systems, which operates in a wide variation of operating scenarios. Energy-efficient design aims to reconfigure its own architectures to scale down energy consumption depending upon the throughput and quality requirement. An energy efficient system should be able to decide its minimum power requirements by dynamically scaling its own operating frequency, supply voltage or the threshold voltage according to a variety of operating scenarios. The increasing product demand for application specific integrated circuit or processor for independent portable devices has influenced designers to implement dedicated processors with ultra low power requirements. One of these dedicated processors is a Fast Fourier Transform (FFT) processor, which is widely used in signal processing for numerous applications such as, wireless telecommunication and biomedical applications where the demand for extended battery life is extremely high. This paper presents the design and performance analysis of a low power shared memory FFT processor incorporating dynamic voltage scaling. Dynamic voltage scaling enables power supply scaling into various supply voltage levels. The concept behind the proposed solution is that if the speed of the main logic core can be adjusted according to input load or amount of processor's computation "just enough" to meet the requirement. The design was implemented using 0.12 μm ST-Microelectronic 6-metal layer CMOS dual- process technology in Cadence Analogue

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

    SciTech Connect

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

    2011-05-01

    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.

  3. Fast Analysis of Molecular Dynamics Trajectories with Graphics Processing Units-Radial Distribution Function Histogramming.

    PubMed

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

    2011-05-01

    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 seconds 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.

  4. Diagnostic Value of 3D Fast Low-Angle Shot Dynamic MRI of Breast Papillomas

    PubMed Central

    Kim, Eun-Kyung; Kim, Jeong-Ah; Kwak, Jin Young; Jeong, Joon

    2009-01-01

    Purpose To evaluate the value of breast MRI in analysis of papillomas of the breast. Materials and Methods From 1996 to 2004, 94 patients underwent surgery due to papillomas of the breast. Among them, 21 patients underwent 3D fast low angle shot (FLASH) dynamic breast MRI. Eight masses were palpable and 11 of 21 patients had nipple discharge. Two radiologists indifferently analyzed the location, size of the lesions and shape, margin of the masses, multiplicity and ductal relation. The MRI findings were categorized according to breast imaging reporting and data system (BI-RADS) lexicon. The amount and pattern of enhancement and associated findings were also evaluated according to BI-RADS. We then compared the MRI findings with galactography, mammography and breast ultrasonography (US) and examined histopathologic correlation. Results On breast MRI, the lesion size was 0.4-1.59 cm, and 18 patients showed subareolar location. On 4.25 cm (mean 1.54) dynamic enhanced images, imaging findings showed mass (n = 10), intracystic mass (n = 3), focus (n = 5), ductal enhancement (n = 2), and segmental enhancement (n = 1). In cases of the masses, the shapes of the masses were round (n = 4), lobulated (n = 3), and irregular (n = 6), and margins were circumscribed (n = 6), microlobulated (n = 5), and indistinct (n = 2). The enhancement patterns were homogeneous enhancement (n = 7), heterogeneous (n = 3) or rim enhancement (n = 3). Conclusion The contrast enhanced dynamic breast MRI was highly sensitive for diagnosis of breast papillomas. MRI could play a key role in the pre-operative work-up for multiple papillomas and papillomatosis. PMID:20046427

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

    SciTech Connect

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

    2001-04-09

    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

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

    SciTech Connect

    Lorenzen, Konstantin; Mathias, Gerald; Tavan, Paul

    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.

  7. Partitioning into Colloidal Structures of Fasted State Intestinal Fluid Studied by Molecular Dynamics Simulations

    PubMed Central

    2016-01-01

    We performed molecular dynamics (MD) simulations to obtain insights into the structure and molecular interactions of colloidal structures present in fasted state intestinal fluid. Drug partitioning and interaction were studied with a mixed system of the bile salt taurocholate (TCH) and 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLiPC). Spontaneous aggregation of TCH and DLiPC from unconstrained MD simulations at the united-atom level using the Berger/Gromos54A7 force fields demonstrated that intermolecular hydrogen bonding between TCH molecules was an important factor in determining the overall TCH and DLiPC configuration. In bilayered systems, these intermolecular hydrogen bonds resulted in embedded transmembrane TCH clusters. Free energy simulations using the umbrella sampling technique revealed that the stability of these transmembrane TCH clusters was superior when they consisted of 3 or 4 TCH per bilayer leaflet. All-atom simulations using the Slipids/GAFF force fields showed that the TCH embedded in the bilayer decreased the energy barrier to penetrate the bilayer (ΔGpen) for water, ethanol, and carbamazepine, but not for the more lipophilic felodipine and danazol. This suggests that diffusion of hydrophilic to moderately lipophilic molecules through the bilayer is facilitated by the embedded TCH molecules. However, the effect of embedded TCH on the overall lipid/water partitioning was significant for danazol, indicating that the incorporation of TCH plays a crucial role for the partitioning of lipophilic solutes into e.g. lipidic vesicles existing in fasted state intestinal fluids. To conclude, the MD simulations revealed important intermolecular interactions in lipidic bilayers, both between the bile components themselves and with the drug molecules. PMID:27934534

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

    PubMed

    Lorenzen, Konstantin; Mathias, Gerald; Tavan, Paul

    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.

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

    NASA Astrophysics Data System (ADS)

    Lorenzen, Konstantin; Mathias, Gerald; Tavan, Paul

    2015-11-01

    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.

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

    PubMed

    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.

  11. Plasma Dynamics and VUV Emission in a Fast Hollow Cathode Capillary Discharge

    NASA Astrophysics Data System (ADS)

    Soto, Leopoldo; Esaulov, Andrey; Silva, Patricio; Sylvester, Gustavo; Moreno, José; Zambra, Marcelo; Nazarenko, Andrey

    2000-10-01

    Following the world tendency to study the physical mechanisms to obtain laser emission in the VUV to soft X-ray region in table-top device, a fast capillary discharge has been constructed at Comisión Chilena de Energía Nuclear, CCHEN. The device is identical to designed by P. Choi and M. Favre, included an electron beam from the hollow cathode region to provide ionization on the axis (1). The discharge operates in Argon with a cathode pressure of 100-500 mtorr. The system works with differential vacuum, thus the anode pressure is around five times less than the cathode pressure. The radius of capillary is 0.4 mm and the length is 2.5 cm. For an applied voltage of 10 kV a peak current of 5 kA with a rise time of 4.8 ns is obtained (10^12 A/s). MHD simulations in order to study the plasma dynamics an temperature evolution were performed (2). A final radius of 100-200 microns is expected at 8 ns, 2 ns after the peak current with a electron density of 2 x 10^18 cm-3. An electron and ion temperature of 80 and 40 eV respectively are predicted. In addition to usual electrical diagnostics, time-space resolution pinhole images (multipinhole camera with a multichannel plate, four frames, one frame every 4 ns) and time resolved spectra in the region of 10 to 100 nm were performed. Dynamics of plasma compresion was studied from time resolved pinhole images. Detected spectra show that plasma consists of argon ions with ionization potential from ArVI to ArX. This work has been funded by FONDECYT grant 1980187 and a Presidential Chair in Science granted by Chilean government. Authors are thankful to K. Koshelev and P. Antsiferov (ISAN, Troitsk) for fruitful discussions and comments. 1.- P. Choi and M. Favre, Rev. Sci. Instrum. 69, 3118, (1998) 2.- A. Esaulov, P. Sasorov, L. Soto, M. Zambra and J. Sakai, ``Fast Hollow Cathode Capillary Discharge. MHD Simulation''. Submitted for publication.

  12. Dynamic optimization of on-chip polymerase chain reaction by monitoring intracycle fluorescence using fast synchronous detection

    NASA Astrophysics Data System (ADS)

    Mondal, Sudip; Paul, Debjani; Venkataraman, V.

    2007-01-01

    The authors report on-chip dynamic optimization of polymerase chain reaction (PCR) based on a feedback technique utilizing synchronous detection of intracycle fluorescence every 500ms. From a direct measurement of polymerase activity, the authors determine the optimum extension temperature. The authors dynamically optimize PCR in an inductively heated microchip by sensing the saturation of extension in each cycle and applying the feedback. They demonstrate that, even with fast ramp rates, dynamic optimization leads to faster reactions compared to fixed-duration extension protocols for long DNA (>500bp). This optimization scheme uses a fairly universal dye Sybr Green I and can be applied to most PCRs.

  13. Fast relaxation dynamics of the cardiotonic drug milrinone in water solutions.

    PubMed

    el-Kemary, Maged; Organero, Juan Angel; Douhal, Abderrazzak

    2006-06-01

    The fast relaxation dynamics of 1,6-dihydro-2-methyl-6-oxo-3,4'-bipyridine-5-carbonitrile (milrinone, MIR), a cardiotonic drug, has been characterized in water solutions at different pH. In acidic media, a blue emission reflects a charge-transfer state in the cation (C) leading to a more stabilized structure with an emission lifetime of 90 ps. The emission lifetimes of the keto (K) and anion (A) structures are approximately 65 and 310 ps, respectively. Reasons for efficient nonradiative channels are discussed in terms of hydrogen-bonding interactions, intramolecular charge transfer (ICT), and twisting motion. A blue nanosecond-emission observed in almost all the studied pH range is suggested to be due to relaxed K due to an ICT reaction. B3LYP (6-31+G**) calculations showed that, in a water cavity, K is more stable than the enol form by 7 kcal/mol, and the ICT may take place within the pyridone moiety. At the physiological pH, the inotropic K structure is the dominant species (approximately 100%).

  14. Utilizing fast multipole expansions for efficient and accurate quantum-classical molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Schwörer, Magnus; Lorenzen, Konstantin; Mathias, Gerald; Tavan, Paul

    2015-03-01

    Recently, a novel approach to hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations has been suggested [Schwörer et al., J. Chem. Phys. 138, 244103 (2013)]. Here, the forces acting on the atoms are calculated by grid-based density functional theory (DFT) for a solute molecule and by a polarizable molecular mechanics (PMM) force field for a large solvent environment composed of several 103-105 molecules as negative gradients of a DFT/PMM hybrid Hamiltonian. The electrostatic interactions are efficiently described by a hierarchical fast multipole method (FMM). Adopting recent progress of this FMM technique [Lorenzen et al., J. Chem. Theory Comput. 10, 3244 (2014)], which particularly entails a strictly linear scaling of the computational effort with the system size, and adapting this revised FMM approach to the computation of the interactions between the DFT and PMM fragments of a simulation system, here, we show how one can further enhance the efficiency and accuracy of such DFT/PMM-MD simulations. The resulting gain of total performance, as measured for alanine dipeptide (DFT) embedded in water (PMM) by the product of the gains in efficiency and accuracy, amounts to about one order of magnitude. We also demonstrate that the jointly parallelized implementation of the DFT and PMM-MD parts of the computation enables the efficient use of high-performance computing systems. The associated software is available online.

  15. Atom ejection from a fast-ion track: A molecular-dynamics study

    SciTech Connect

    Urbassek, H.M. ); Kafemann, H. ); Johnson, R.E. )

    1994-01-01

    As a model for atom ejection from fast-ion tracks, molecular-dynamics simulations of a cylindrical track of energized particles are performed. An idealized situation is studied where every atom in a cylindrical track of radius [ital R][sub 0] is energized with energy [ital E][sub 0]. The emission yield [ital Y]([ital E][sub 0],[ital R][sub 0]) shows the existence of two ejection regimes. If the particle energy [ital E][sub 0] is below the sublimation energy [ital U] of the material, a threshold regime is seen in which [ital Y] rises roughly like the third power of [ital E][sub 0]; for high-energy densities [ital E][sub 0][approx gt][ital U], the yield rises much more slowly, roughly linearly. In both cases, ejected particles mostly originate from the track, rather than from its surroundings, and from the first or the first few monolayers. The behavior found is interpreted here in terms of emission due to a pressure-driven jet (linear regime) or due to a pressure pulse (threshold regime). These both behave differently from the often-used thermal-spike sputtering model.

  16. DCEMRI.jl: a fast, validated, open source toolkit for dynamic contrast enhanced MRI analysis

    PubMed Central

    Li, Xia; Arlinghaus, Lori R.; Yankeelov, Thomas E.; Welch, E. Brian

    2015-01-01

    We present a fast, validated, open-source toolkit for processing dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data. We validate it against the Quantitative Imaging Biomarkers Alliance (QIBA) Standard and Extended Tofts-Kety phantoms and find near perfect recovery in the absence of noise, with an estimated 10–20× speedup in run time compared to existing tools. To explain the observed trends in the fitting errors, we present an argument about the conditioning of the Jacobian in the limit of small and large parameter values. We also demonstrate its use on an in vivo data set to measure performance on a realistic application. For a 192 × 192 breast image, we achieved run times of <1 s. Finally, we analyze run times scaling with problem size and find that the run time per voxel scales as O(N1.9), where N is the number of time points in the tissue concentration curve. DCEMRI.jl was much faster than any other analysis package tested and produced comparable accuracy, even in the presence of noise. PMID:25922795

  17. Utilizing fast multipole expansions for efficient and accurate quantum-classical molecular dynamics simulations

    SciTech Connect

    Schwörer, Magnus; Lorenzen, Konstantin; Mathias, Gerald; Tavan, Paul

    2015-03-14

    Recently, a novel approach to hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations has been suggested [Schwörer et al., J. Chem. Phys. 138, 244103 (2013)]. Here, the forces acting on the atoms are calculated by grid-based density functional theory (DFT) for a solute molecule and by a polarizable molecular mechanics (PMM) force field for a large solvent environment composed of several 10{sup 3}-10{sup 5} molecules as negative gradients of a DFT/PMM hybrid Hamiltonian. The electrostatic interactions are efficiently described by a hierarchical fast multipole method (FMM). Adopting recent progress of this FMM technique [Lorenzen et al., J. Chem. Theory Comput. 10, 3244 (2014)], which particularly entails a strictly linear scaling of the computational effort with the system size, and adapting this revised FMM approach to the computation of the interactions between the DFT and PMM fragments of a simulation system, here, we show how one can further enhance the efficiency and accuracy of such DFT/PMM-MD simulations. The resulting gain of total performance, as measured for alanine dipeptide (DFT) embedded in water (PMM) by the product of the gains in efficiency and accuracy, amounts to about one order of magnitude. We also demonstrate that the jointly parallelized implementation of the DFT and PMM-MD parts of the computation enables the efficient use of high-performance computing systems. The associated software is available online.

  18. Multi-GeV electron radiography for measurements of fast dynamic systems

    NASA Astrophysics Data System (ADS)

    Merrill, F. E.; Fabritius, J.; Mariam, F. G.; Poulson, D.; Simpson, R.; Walstrom, P.; Wilde, C.

    2017-01-01

    Charged particle radiography has been developed in the past decade to provide high-resolution, muti-frame flash radiography of dynamic systems. This development has focused on proton radiography utilizing 11 MeV to 50 GeV protons for a wide range of measurements. Recently, these techniques are being applied to the use of high energy electrons for applications at a future LANL MaRIE facility. At MaRIE Multi-GeV electrons may be used to diagnose small, quickly evolving systems, requiring resolution and frame rates beyond the capability of the existing 800 MeV proton radiography. The electron accelerator proposed for MaRIE will be capable of meeting the fast frame rate and resolution requirements for MaRIE. Because of the light mass of the electrons, bremsstrahlung processes become dominant in the electron interactions within the material being studied. Simulations have been performed to study these interactions, but measurements are required to fully understand the capabilities of this new measurement technique. We present an estimate from simulations of the performance characteristics of this future capability.

  19. Fast dynamic electron paramagnetic resonance (EPR) oxygen imaging using low-rank tensors

    NASA Astrophysics Data System (ADS)

    Christodoulou, Anthony G.; Redler, Gage; Clifford, Bryan; Liang, Zhi-Pei; Halpern, Howard J.; Epel, Boris

    2016-09-01

    Hypoxic tumors are resistant to radiotherapy, motivating the development of tools to image local oxygen concentrations. It is generally believed that stable or chronic hypoxia is the source of resistance, but more recent work suggests a role for transient hypoxia. Conventional EPR imaging (EPRI) is capable of imaging tissue pO2in vivo, with high pO2 resolution and 1 mm spatial resolution but low imaging speed (10 min temporal resolution for T1-based pO2 mapping), which makes it difficult to investigate the oxygen changes, e.g., transient hypoxia. Here we describe a new imaging method which accelerates dynamic EPR oxygen imaging, allowing 3D imaging at 2 frames per minute, fast enough to image transient hypoxia at the "speed limit" of observed pO2 change. The method centers on a low-rank tensor model that decouples the tradeoff between imaging speed, spatial coverage/resolution, and number of inversion times (pO2 accuracy). We present a specialized sparse sampling strategy and image reconstruction algorithm for use with this model. The quality and utility of the method is demonstrated in simulations and in vivo experiments in tumor bearing mice.

  20. Dynamic Pore-scale Reservoir-condition Imaging of Reaction in Carbonates Using Synchrotron Fast Tomography.

    PubMed

    Menke, Hannah P; Andrew, Matthew G; Vila-Comamala, Joan; Rau, Christoph; Blunt, Martin J; Bijeljic, Branko

    2017-02-21

    Underground storage permanence is a major concern for carbon capture and storage. Pumping CO2 into carbonate reservoirs has the potential to dissolve geologic seals and allow CO2 to escape. However, the dissolution processes at reservoir conditions are poorly understood. Thus, time-resolved experiments are needed to observe and predict the nature and rate of dissolution at the pore scale. Synchrotron fast tomography is a method of taking high-resolution time-resolved images of complex pore structures much more quickly than traditional µ-CT. The Diamond Lightsource Pink Beam was used to dynamically image dissolution of limestone in the presence of CO2-saturated brine at reservoir conditions. 100 scans were taken at a 6.1 µm resolution over a period of 2 hours. The images were segmented and the porosity and permeability were measured using image analysis and network extraction. Porosity increased uniformly along the length of the sample; however, the rate of increase of both porosity and permeability slowed at later times.

  1. Molecular dynamics and intracellular signaling of the TNF-R1 with the R92Q mutation.

    PubMed

    Agulló, Luis; Malhotra, Sunny; Fissolo, Nicolás; Montalban, Xavier; Comabella, Manuel

    2015-12-15

    The tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A) gene encodes the TNF-R1, one of the main TNF receptors that mediates its inflammatory actions. In a recent study, serum levels of the soluble TNF-R1 and mRNA levels of the full-length receptor were found to be significantly increased in multiple sclerosis (MS) patients carrying the R92Q mutation. Interestingly, R92Q-mutated patients were younger at disease onset and progressed slower as compared to non-carriers. Building on these previous findings, here we aimed to investigate by means of both in silico and in vitro approaches the mechanisms relating the R92Q substitution with functional changes of the receptor and their potential effects modulating MS disease course. Models of the extracellular domains of the human TNF-R1 and human TNF-R1 carrying the R92Q mutation, alone or bound to TNF, were constructed and submitted to molecular dynamics. TRAF2 and CASP3 mRNA expression levels were determined by real-time PCR in peripheral blood mononuclear cells (PBMC) from 61 MS patients, 9 R92Q carriers and 52 non-carriers (CT and CC genotypes for SNP rs4149584, respectively). Molecular dynamic studies revealed that the R92Q mutation increased the contact area between receptor and TNF (1070 and 1388Å(2) for native and mutated receptor) and decreased the distance between them (28.7 to 27.9Å), while Van der Waals and electrostatic interaction energies were increased. In PBMC from MS patients carrying the R92Q mutation, CASP3 mRNA expression levels were significantly increased compared to non-carriers, whereas a trend was observed for TRAF2. These data suggest that the R92Q mutation gives rise to a stronger interaction between the receptor and its ligand, which results in the potentiation of TNF-mediated pathways. Although further studies are needed, these functional changes may be related with the modulation in disease course reported in MS patients carrying the R92Q mutation.

  2. Calibration and Validation of a Spar-Type Floating Offshore Wind Turbine Model using the FAST Dynamic Simulation Tool: Preprint

    SciTech Connect

    Browning, J. R.; Jonkman, J.; Robertson, A.; Goupee, A. J.

    2012-11-01

    In 2007, the FAST wind turbine simulation tool, developed and maintained by the U.S. Department of Energy's (DOE's) National Renewable Energy Laboratory (NREL), was expanded to include capabilities that are suitable for modeling floating offshore wind turbines. In an effort to validate FAST and other offshore wind energy modeling tools, DOE funded the DeepCwind project that tested three prototype floating wind turbines at 1/50th scale in a wave basin, including a semisubmersible, a tension-leg platform, and a spar buoy. This paper describes the use of the results of the spar wave basin tests to calibrate and validate the FAST offshore floating simulation tool, and presents some initial results of simulated dynamic responses of the spar to several combinations of wind and sea states.

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Extended Vofire algorithm for fast transient fluid-structure dynamics with liquid-gas flows and interfaces

    NASA Astrophysics Data System (ADS)

    Faucher, Vincent; Kokh, Samuel

    2013-05-01

    The present paper is dedicated to the simulation of liquid-gas flows with interfaces in the framework of fast transient fluid-structure dynamics. The two-fluid interface is modelled as a discontinuity surface in the fluid property. We use an anti-dissipative Finite-Volume discretization strategy for unstructured meshes in order to capture the position of the interface within a thin diffused volume. This allows to control the numerical diffusion of the artificial mixing between components and provide an accurate capture of complex interface motions. This scheme is an extension of the Vofire numerical solver. We propose specific developments in order to handle flows that involved high density ratio between liquid and gas. The resulting scheme capabilities are validated on basic examples and also tested against large scale fluid-structure test derived from the MARA 10 experiment. All simulations are performed using EUROPLEXUS fast transient dynamics software.

  5. Automatic brain tumor extraction from T1-weighted coronal MRI using fast bounding box and dynamic snake.

    PubMed

    Xu, Tao; Mandal, Mrinal

    2012-01-01

    Brain tumor segmentation from MRI data is an important but challenging task. This paper presents an efficient and fully automatic brain tumor segmentation technique. The proposed technique includes a fuzzy C-means (FCM) based preprocessing to enhance the quality of T1-weighted coronal MR images, a fast bounding box (FBB) detection algorithm to locate a rectangle around tumor, and a new dynamic snake using modified Hausdorff distance (MHD) for the final tumor extraction.

  6. Calibration and validation of a spar-type floating offshore wind turbine model using the FAST dynamic simulation tool

    NASA Astrophysics Data System (ADS)

    Browning, J. R.; Jonkman, J.; Robertson, A.; Goupee, A. J.

    2014-12-01

    High-quality computer simulations are required when designing floating wind turbines because of the complex dynamic responses that are inherent with a high number of degrees of freedom and variable metocean conditions. In 2007, the FAST wind turbine simulation tool, developed and maintained by the U.S. Department of Energy's (DOE's) National Renewable Energy Laboratory (NREL), was expanded to include capabilities that are suitable for modeling floating offshore wind turbines. In an effort to validate FAST and other offshore wind energy modeling tools, DOE funded the DeepCwind project that tested three prototype floating wind turbines at 1/50th scale in a wave basin, including a semisubmersible, a tension-leg platform, and a spar buoy. This paper describes the use of the results of the spar wave basin tests to calibrate and validate the FAST offshore floating simulation tool, and presents some initial results of simulated dynamic responses of the spar to several combinations of wind and sea states. Wave basin tests with the spar attached to a scale model of the NREL 5-megawatt reference wind turbine were performed at the Maritime Research Institute Netherlands under the DeepCwind project. This project included free-decay tests, tests with steady or turbulent wind and still water (both periodic and irregular waves with no wind), and combined wind/wave tests. The resulting data from the 1/50th model was scaled using Froude scaling to full size and used to calibrate and validate a full-size simulated model in FAST. Results of the model calibration and validation include successes, subtleties, and limitations of both wave basin testing and FAST modeling capabilities.

  7. Calibration and validation of a spar-type floating offshore wind turbine model using the FAST dynamic simulation tool

    SciTech Connect

    Browning, J. R.; Jonkman, J.; Robertson, A.; Goupee, A. J.

    2014-12-16

    In this study, high-quality computer simulations are required when designing floating wind turbines because of the complex dynamic responses that are inherent with a high number of degrees of freedom and variable metocean conditions. In 2007, the FAST wind turbine simulation tool, developed and maintained by the U.S. Department of Energy's (DOE's) National Renewable Energy Laboratory (NREL), was expanded to include capabilities that are suitable for modeling floating offshore wind turbines. In an effort to validate FAST and other offshore wind energy modeling tools, DOE funded the DeepCwind project that tested three prototype floating wind turbines at 1/50th scale in a wave basin, including a semisubmersible, a tension-leg platform, and a spar buoy. This paper describes the use of the results of the spar wave basin tests to calibrate and validate the FAST offshore floating simulation tool, and presents some initial results of simulated dynamic responses of the spar to several combinations of wind and sea states. Wave basin tests with the spar attached to a scale model of the NREL 5-megawatt reference wind turbine were performed at the Maritime Research Institute Netherlands under the DeepCwind project. This project included free-decay tests, tests with steady or turbulent wind and still water (both periodic and irregular waves with no wind), and combined wind/wave tests. The resulting data from the 1/50th model was scaled using Froude scaling to full size and used to calibrate and validate a full-size simulated model in FAST. Results of the model calibration and validation include successes, subtleties, and limitations of both wave basin testing and FAST modeling capabilities.

  8. Calibration and validation of a spar-type floating offshore wind turbine model using the FAST dynamic simulation tool

    DOE PAGES

    Browning, J. R.; Jonkman, J.; Robertson, A.; ...

    2014-12-16

    In this study, high-quality computer simulations are required when designing floating wind turbines because of the complex dynamic responses that are inherent with a high number of degrees of freedom and variable metocean conditions. In 2007, the FAST wind turbine simulation tool, developed and maintained by the U.S. Department of Energy's (DOE's) National Renewable Energy Laboratory (NREL), was expanded to include capabilities that are suitable for modeling floating offshore wind turbines. In an effort to validate FAST and other offshore wind energy modeling tools, DOE funded the DeepCwind project that tested three prototype floating wind turbines at 1/50th scale inmore » a wave basin, including a semisubmersible, a tension-leg platform, and a spar buoy. This paper describes the use of the results of the spar wave basin tests to calibrate and validate the FAST offshore floating simulation tool, and presents some initial results of simulated dynamic responses of the spar to several combinations of wind and sea states. Wave basin tests with the spar attached to a scale model of the NREL 5-megawatt reference wind turbine were performed at the Maritime Research Institute Netherlands under the DeepCwind project. This project included free-decay tests, tests with steady or turbulent wind and still water (both periodic and irregular waves with no wind), and combined wind/wave tests. The resulting data from the 1/50th model was scaled using Froude scaling to full size and used to calibrate and validate a full-size simulated model in FAST. Results of the model calibration and validation include successes, subtleties, and limitations of both wave basin testing and FAST modeling capabilities.« less

  9. New Structural-Dynamics Module for Offshore Multimember Substructures within the Wind Turbine Computer-Aided Engineering Tool FAST: Preprint

    SciTech Connect

    Song, H.; Damiani, R.; Robertson, A.; Jonkman, J.

    2013-08-01

    FAST, developed by the National Renewable Energy Laboratory (NREL), is a computer-aided engineering (CAE) tool for aero-hydro-servo-elastic analysis of land-based and offshore wind turbines. This paper discusses recent upgrades made to FAST to enable loads simulations of offshore wind turbines with fixed-bottom, multimember support structures (e.g., jackets and tripods, which are commonly used in transitional-depth waters). The main theory and strategies for the implementation of the multimember substructure dynamics module (SubDyn) within the new FAST modularization framework are introduced. SubDyn relies on two main engineering schematizations: 1) a linear frame finite-element beam (LFEB) model and 2) a dynamics system reduction via Craig-Bampton's method. A jacket support structure and an offshore system consisting of a turbine atop a jacket substructure were simulated to test the SubDyn module and to preliminarily assess results against results from a commercial finite-element code.

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

    SciTech Connect

    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.

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

    SciTech Connect

    Li, Runbing; Zhu, Chengjie; Deng, L.; Hagley, E. W.

    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.

  12. Dynamics of water solutions of natural polysaccharides by fast field cycling nmr relaxometry

    NASA Astrophysics Data System (ADS)

    Prusova, Alena; Conte, Pellegrino; Kucerik, Jiri; de Pasquale, Claudio; Alonzo, Giuseppe

    2010-05-01

    Cryobiology studies the effect of low temperatures on living systems such as microorganisms and plants. In particular, plants growing in cold or frozen environments can survive such extreme conditions due to the cold hardening process. Hardening is a three step process during which, first, translocation of polysaccharides to the plant roots affects water structure in the cell-soil surface. For this reason, increase of cell-membrane permeability and resistance to temperatures from -5°C to -10°C is achieved. In a second step, chemical alteration of cell membrane arises and resistance to temperatures up to -20°C is obtained. The last hardening step consists in the vitrification of the plant tissues which allow plants to survive at temperatures as low as -50°C. Since polysaccharides play a very important role in the initial part of the cold hardening process, it is of paramount importance to study the effect of such natural biopolymers on water structure. Here, we present preliminary data obtained by fast field cycling NMR relaxometry on the effect of hyaluronan (an anionic, non-sulfated glycosaminoglycan) on water structure at different concentrations of the polysaccharide. Although hyaluronan is a polysaccharide found exceptionally in animal, human or bacterial bodies, in the present work it was used as a model "pilot" compound. In fact, it has an unique ability to hold water and it contains both polysaccharide and protein-like acetamido functionalities. For this reason, hyaluronan promotes the future research on other plant biopolymers such as, for instance, starch and other very specific proteins. Results revealed that different water-structure systems surround the molecule of hyaluronan in diluted and semidiluted systems. Namely, at the lowest hyaluronan concentration, three hydration shells can be recognized. The first hydration shell is made by bound water (BW) which is strongly fixed to the hyaluronan surface mainly through electrostatic interactions. A

  13. A fast and explicit algorithm for simulating the dynamics of small dust grains with smoothed particle hydrodynamics

    NASA Astrophysics Data System (ADS)

    Price, Daniel J.; Laibe, Guillaume

    2015-07-01

    We describe a simple method for simulating the dynamics of small grains in a dusty gas, relevant to micron-sized grains in the interstellar medium and grains of centimetre size and smaller in protoplanetary discs. The method involves solving one extra diffusion equation for the dust fraction in addition to the usual equations of hydrodynamics. This `diffusion approximation for dust' is valid when the dust stopping time is smaller than the computational timestep. We present a numerical implementation using smoothed particle hydrodynamics that is conservative, accurate and fast. It does not require any implicit timestepping and can be straightforwardly ported into existing 3D codes.

  14. Supramolecular nanoreactors for intracellular singlet-oxygen sensitization

    NASA Astrophysics Data System (ADS)

    Swaminathan, Subramani; Fowley, Colin; Thapaliya, Ek Raj; McCaughan, Bridgeen; Tang, Sicheng; Fraix, Aurore; Burjor, Captain; Sortino, Salvatore; Callan, John F.; Raymo, Françisco M.

    2015-08-01

    An amphiphilic polymer with multiple decyl and oligo(ethylene glycol) chains attached to a common poly(methacrylate) backbone assembles into nanoscaled particles in aqueous environments. Hydrophobic anthracene and borondipyrromethene (BODIPY) chromophores can be co-encapsulated within the self-assembling nanoparticles and transported across hydrophilic media. The reversible character of the noncovalent bonds, holding the supramolecular containers together, permits the exchange of their components with fast kinetics in aqueous solution. Incubation of cervical cancer (HeLA) cells with a mixture of two sets of nanoparticles, pre-loaded independently with anthracene or BODIPY chromophores, results in guest scrambling first and then transport of co-entrapped species to the intracellular space. Alternatively, incubation of cells with the two sets of nanocarriers in consecutive steps permits the sequential transport of the anthracene and BODIPY chromophores across the plasma membrane and only then allows their co-encapsulation within the same supramolecular containers. Both mechanisms position the two sets of chromophores with complementary spectral overlap in close proximity to enable the efficient transfer of energy intracellularly from the anthracene donors to the BODIPY acceptors. In the presence of iodine substituents on the BODIPY platform, intersystem crossing follows energy transfer. The resulting triplet state can transfer energy further to molecular oxygen with the concomitant production of singlet oxygen to induce cell mortality. Furthermore, the donor can be excited with two near-infrared photons simultaneously to permit the photoinduced generation of singlet oxygen intracellularly under illumination conditions compatible with applications in vivo. Thus, these supramolecular strategies to control the excitation dynamics of multichromophoric assemblies in the intracellular environment can evolve into valuable protocols for photodynamic therapy.An amphiphilic

  15. Gas Dynamics, Characterization, and Calibration of Fast Flow Flight Cascade Impactor Quartz Crystal Microbalances (QCM) for Aerosol Measurements

    NASA Technical Reports Server (NTRS)

    Grant, J.R.; Thorpe, A. N.; James, C.; Michael, A.; Ware, M.; Senftle, F.; Smith, S.

    1997-01-01

    During recent high altitude flights, we have tested the aerosol section of the fast flow flight cascade impactor quartz crystal microbalance (QCM) on loan to Howard University from NASA. The aerosol mass collected during these flights was disappointingly small. Increasing the flow through the QCM did not correct the problem. It was clear that the instrument was not being operated under proper conditions for aerosol collect ion primarily because the gas dynamics is not well understood. A laboratory study was therefore undertaken using two different fast flow QCM's in an attempt to establish the gas flow characteristics of the aerosol sections and its effect on particle collection, Some tests were made at low temperatures but most of the work reported here was carried out at room temperature. The QCM is a cascade type impactor originally designed by May (1945) and later modified by Anderson (1966) and Mercer et al (1970) for chemical gas analysis. The QCM has been used extensively for collecting and sizing stratospheric aerosol particles. In this paper all flow rates are given or corrected and referred to in terms of air at STP. All of the flow meters were kept at STP. Although there have been several calibration and evaluation studies of moderate flow cascade impactors of less than or equal to 1 L/rein., there is little experimental information on the gas flow characteristics for fast flow rates greater than 1 L/rein.

  16. Computational fluid dynamics modelling of biomass fast pyrolysis in fluidised bed reactors, focusing different kinetic schemes.

    PubMed

    Ranganathan, Panneerselvam; Gu, Sai

    2016-08-01

    The present work concerns with CFD modelling of biomass fast pyrolysis in a fluidised bed reactor. Initially, a study was conducted to understand the hydrodynamics of the fluidised bed reactor by investigating the particle density and size, and gas velocity effect. With the basic understanding of hydrodynamics, the study was further extended to investigate the different kinetic schemes for biomass fast pyrolysis process. The Eulerian-Eulerian approach was used to model the complex multiphase flows in the reactor. The yield of the products from the simulation was compared with the experimental data. A good comparison was obtained between the literature results and CFD simulation. It is also found that CFD prediction with the advanced kinetic scheme is better when compared to other schemes. With the confidence obtained from the CFD models, a parametric study was carried out to study the effect of biomass particle type and size and temperature on the yield of the products.

  17. Fast continuous energy scan with dynamic coupling of the monochromator and undulator at the DEIMOS beamline.

    PubMed

    Joly, L; Otero, E; Choueikani, F; Marteau, F; Chapuis, L; Ohresser, P

    2014-05-01

    In order to improve the efficiency of X-ray absorption data recording, a fast scan method, the Turboscan, has been developed on the DEIMOS beamline at Synchrotron SOLEIL, consisting of a software-synchronized continuous motion of the monochromator and undulator motors. This process suppresses the time loss when waiting for the motors to reach their target positions, as well as software dead-time, while preserving excellent beam characteristics.

  18. NMR signal enhancement of >50 000 times in fast dissolution dynamic nuclear polarization.

    PubMed

    Pinto, L F; Marín-Montesinos, I; Lloveras, V; Muñoz-Gómez, J L; Pons, M; Veciana, J; Vidal-Gancedo, J

    2017-03-17

    Herein, we report the synthesis and the study of a novel mixed biradical with BDPA and TEMPO radical units that are covalently bound by an ester group (BDPAesterTEMPO) as a polarizing agent for fast dissolution DNP. The biradical exhibits an extremely high DNP NMR enhancement of >50 000 times, which constitutes one of the largest signal enhancements observed so far, to the best of our knowledge.

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

    NASA Astrophysics Data System (ADS)

    Salewski, M.; Geiger, B.; Jacobsen, A. S.; Hansen, P. C.; Heidbrink, W. W.; Korsholm, S. B.; Leipold, F.; Madsen, J.; Moseev, D.; Nielsen, S. K.; Nocente, M.; Odstrčil, T.; Rasmussen, J.; Stagner, L.; Stejner, M.; Weiland, M.; the ASDEX Upgrade Team

    2016-10-01

    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 D α (FIDA) spectroscopy as well as the strive for high-resolution images. In high-definition tomography, prior information makes up for this lack of data. We restrict the target velocity space through the measured absence of FIDA light, impose phase-space densities to be non-negative, and encode the known geometry of neutral beam injection (NBI) sources. We further use a numerical simulation as prior 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 peaks at full, half and one-third energy by time-resolved tomographic movies.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

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

    SciTech Connect

    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.

    2009-10-15

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

    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.

  4. A Fast Algorithm for Massively Parallel, Long-Term, Simulation of Complex Molecular Dynamics Systems

    NASA Technical Reports Server (NTRS)

    Jaramillo-Botero, Andres; Goddard, William A, III; Fijany, Amir

    1997-01-01

    The advances in theory and computing technology over the last decade have led to enormous progress in applying atomistic molecular dynamics (MD) methods to the characterization, prediction, and design of chemical, biological, and material systems,.

  5. Inclusion-localised crystal-plasticity, dynamic porosity, and fast-diffusion pathway generation in zircon

    NASA Astrophysics Data System (ADS)

    Timms, Nicholas E.; Reddy, Steven M.; Fitz Gerald, John D.; Green, Leonard; Muhling, Janet R.

    2012-02-01

    A population of oscillatory zoned, igneous zircon grains in a Javanese andesite contains fluid and mineral inclusions (up to 10 μm across) trapped during zircon growth. Orientation contrast imaging and orientation mapping by electron backscatter diffraction reveal that crystal-plastic deformation overprints growth zoning and has localized around 1-10 μm pores and inclusions. Cumulative crystallographic misorientation of up to 25° around pores and inclusions in zircon is predominantly accommodated by low-angle (<5°) orientation boundaries, with few free dislocations in subgrain interiors. Low-angle boundaries are curved, with multiple orientation segments at the sub-micrometer scale. Misorientation axes associated with the most common boundaries align with the zircon c-axis and are consistent with dislocation creep dominated by <100>(010) slip. A distinctly different population of sub-micron pores is present along subgrain boundaries and their triple junctions. These are interpreted to have formed as a geometric consequence of dislocation interaction during crystal-plasticity. Dislocation creep microstructures are spatially related to differences in cathodoluminescence spectra that indicate variations in the abundance of CL-active rare earth elements. The extent of the modification suggests deformation-related fast-pathway diffusion distances that are over five orders of magnitude greater than expected for volume diffusion. This enhanced diffusion is interpreted to represent a combination of fast-diffusion pathways associated with creep cavitation, dislocations and along low-angle boundaries. These new data indicate that ductile deformation localised around inclusions can provide fast pathways for geochemical exchange. These pathways may provide links to the zircon grain boundary, thus negating the widely held assumption that inclusions in fracture-free zircon are geochemically armoured once they are physically enclosed.

  6. Geometry and dynamics of fast magnetosonic wavefronts near magnetic null points

    NASA Astrophysics Data System (ADS)

    Núñez, Manuel

    2017-02-01

    The behavior of two-dimensional fast magnetosonic waves in the vicinity of isolated points where the magnetic field vanishes is studied analytically. The geometry of rays and wavefronts is described, and the curvature of both is found using conformal mapping techniques. These results are applied to the formation of shock waves, obtaining that shock formation is guaranteed at a finite time for any initial condition of the perturbation when the wavefront is concave and the rays tend to focus, whereas otherwise shocks occur only for a certain range of initial conditions.

  7. Fast and flexible interpolation via PUM with applications in population dynamics

    NASA Astrophysics Data System (ADS)

    Cavoretto, Roberto; De Rossi, Alessandra; Perracchione, Emma

    2016-06-01

    In this paper a new fast and flexible interpolation tool is shown. The Partition of Unity Method (PUM) is performed using Radial Basis Functions (RBFs) as local approximants. In particular, we present a new space-partitioning data structure extremely useful in applications because of its independence from the problem geometry. An application of such algorithm, in the context of wild herbivores in forests, shows that the ecosystem of the considered natural park is in a very delicate situation, for which the animal population could become extinguished. The determination of the so-called sensitivity surfaces, obtained with the new versatile partitioning structure, indicates some possible preventive measures to the park administrators.

  8. Fast time-reversible algorithms for molecular dynamics of rigid-body systems

    NASA Astrophysics Data System (ADS)

    Kajima, Yasuhiro; Hiyama, Miyabi; Ogata, Shuji; Kobayashi, Ryo; Tamura, Tomoyuki

    2012-06-01

    In this paper, we present time-reversible simulation algorithms for rigid bodies in the quaternion representation. By advancing a time-reversible algorithm [Y. Kajima, M. Hiyama, S. Ogata, and T. Tamura, J. Phys. Soc. Jpn. 80, 114002 (2011), 10.1143/JPSJ.80.114002] that requires iterations in calculating the angular velocity at each time step, we propose two kinds of iteration-free fast time-reversible algorithms. They are easily implemented in codes. The codes are compared with that of existing algorithms through demonstrative simulation of a nanometer-sized water droplet to find their stability of the total energy and computation speeds.

  9. Studying IDP stability and dynamics by fast relaxation imaging in living cells.

    PubMed

    Dhar, Apratim; Prigozhin, Maxim; Gelman, Hannah; Gruebele, Martin

    2012-01-01

    Fast relaxation imaging (FReI) temperature-tunes living cells and applies small temperature jumps to them, to monitor biomolecular stability and kinetics in vivo. The folding or aggregation state of a target protein is monitored by Förster resonance energy transfer (FRET). Intrinsically disordered proteins near the structured-unstructured boundary are particularly sensitive to their environment. We describe, using the IDP α-synuclein as an example, how FReI can be used to measure IDP stability and folding inside the cell.

  10. Anomalous fast dynamics of adsorbate overlayers near an incommensurate structural transition.

    PubMed

    Granato, Enzo; Ying, S C; Elder, K R; Ala-Nissila, T

    2013-09-20

    We investigate the dynamics of a compressively strained adsorbed layer on a periodic substrate via a simple two-dimensional model that admits striped and hexagonal incommensurate phases. We show that the mass transport is superfast near the striped-hexagonal phase boundary and in the hexagonal phase. For an initial step profile separating a bare substrate region (or "hole") from the rest of a striped incommensurate phase, the superfast domain wall dynamics leads to a bifurcation of the initial step profile into two interfaces or profiles propagating in opposite directions with a hexagonal phase in between. This yields a theoretical understanding of the recent experiments for the Pb/Si(111) system.

  11. The effect of fault segmentation on the dynamics of fast-slipping oceanic transform faults

    NASA Astrophysics Data System (ADS)

    Gregg, P. M.; Behn, M. D.; Lin, J.; Grove, T. L.; Montési, L. G.

    2007-12-01

    The majority of oceanic transform faults (OTFs) systems along the fast-spreading equatorial East Pacific Rise are segmented into two or more strike-slip fault strands as a result of plate motion reorganization. Fresh basaltic lava sampled from these locations (e.g., the Siqueiros and Garrett OTFs) indicate that active crustal accretion is occurring within these transform systems. New Residual Mantle Bouguer gravity Anomalies (RMBA) calculated along fast-slipping OTFs are found to be more negative than the RMBA values along adjacent ridge segments. One possible explanation for these observations is enhanced magmatic upwelling and crustal accretion at intra- transform spreading centers (ITSC) and within the transform valley of the fast-slipping OTFs. In this study, we examine two end-member 3-D thermal models (constant viscosity rheology versus visco-plastic rheology) to explore mantle flow and melt extraction beneath segmented transform faults. Melt fraction is calculated using the parameterized fractional melting model of Kinzler and Grove (JGR, 1992a, 1992b, and 1993), and the fractional crystallization models of Yang et al. (Cont. Min. Pet., 1996). We evaluate the sensitivity of these models to various parameters including transform fault geometry, mantle potential temperature, and initial mantle composition. Preliminary results for a 100 km-long transform fault, slipping at 100 mm/yr, segmented by a single 10 km-long ITSC indicate that incorporating a visco-plastic rheology results in an approximately 35 percent decrease in the brittle fault area (< 600°C isotherm) compared to a constant viscosity model. Assuming upward melt migration along the base of the lithosphere, we find that crustal production is enhanced at ITSC by 1-1.5 km compared to the adjacent ridge segments. However, crustal thickness variations are sensitive to transform fault geometry and assumptions made about the pooled melt region. For example, if melt migration is not permitted across the

  12. Dynamics of the Axial Melt Lens/Dike transition at fast spreading ridges: assimilation and hydrous partial melting

    NASA Astrophysics Data System (ADS)

    France, L.; Ildefonse, B.; Koepke, J.

    2009-04-01

    Recent detailed field studies performed in the Oman ophiolite on the gabbro/sheeted dike transition, compared to corresponding rocks from the EPR drilled by IODP (Site 1256), constrain a general model for the dynamics of the axial melt lens (AML) present at fast spreading ridges (France et al., 2008). This model implies that the AML/dike transition is a dynamic interface migrating up- and downward, and that the isotropic gabbro horizon on top of the igneous section represents its fossilization. It is also proposed that upward migrations are associated to reheating of the base of the sheeted dike complex and to assimilation processes. Plagiogranitic lithologies are observed close to the truncated base of the dikes and are interpreted to represent frozen melts generated by partial melting of previously hydrothermalized sheeted dikes. Relicts of previously hydrothermalized lithologies are also observed in the fossil melt lens, and are associated to lithologies that have crystallized under high water activities, with clinopyroxene crystallizing before plagioclase, and An-rich plagioclase. To better understand our field data, we performed hydrous partial melting experiments at shallow pressures (0.1 GPa) under slightly oxidizing conditions (NNO oxygen buffer) and water saturated conditions on hydrothermalized sheeted dike sample from the Oman ophiolite. These experiments have been performed between 850°C and 1030°C; two additional experiments in the subsolidus regime were also conducted (750°C and 800°C). Clinopyroxenes formed during incongruent melting at low temperature (<910°C) have compositions that match those from the corresponding natural rocks (reheated base of the sheeted dike and relicts of assimilated lithologies). In particular, the characteristic low TiO2 and Al2O3 contents are reproduced. The experimental melts produced at low temperatures correspond to compositions of typical natural plagiogranites. In natural settings, these silicic liquids would be

  13. Intracellular siRNA delivery dynamics of integrin-targeted, PEGylated chitosan-poly(ethylene imine) hybrid nanoparticles: A mechanistic insight.

    PubMed

    Ragelle, Héloïse; Colombo, Stefano; Pourcelle, Vincent; Vanvarenberg, Kevin; Vandermeulen, Gaëlle; Bouzin, Caroline; Marchand-Brynaert, Jacqueline; Feron, Olivier; Foged, Camilla; Préat, Véronique

    2015-08-10

    Integrin-targeted nanoparticles are promising for the delivery of small interfering RNA (siRNA) to tumor cells or tumor endothelium in cancer therapy aiming at silencing genes essential for tumor growth. However, during the process of optimizing and realizing their full potential, it is pertinent to gain a basic mechanistic understanding of the bottlenecks existing for nanoparticle-mediated intracellular delivery. We designed αvβ3 integrin-targeted nanoparticles by coupling arginine-glycine-aspartate (RGD) or RGD peptidomimetic (RGDp) ligands to the surface of poly(ethylene glycol) (PEG) grafted 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 transcription quantitative polymerase chain reaction (RT-qPCR) approach. Data demonstrated that the internalization of αvβ3-targeted nanoparticles was highly dependent on the surface concentration of the ligand. Above a certain threshold concentration, the use of targeted nanoparticles provided a two-fold increase in the number of siRNA copies/cell, subsequently resulting in as much as 90% silencing of EGFP at well-tolerated carrier concentrations. In contrast, non-targeted nanoparticles mediated low levels of gene silencing, despite relatively high intracellular siRNA concentrations, indicating 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 a more complete understanding of the delivery mechanism that can facilitate the future design of efficient siRNA delivery systems.

  14. Supramolecular nanoreactors for intracellular singlet-oxygen sensitization.

    PubMed

    Swaminathan, Subramani; Fowley, Colin; Thapaliya, Ek Raj; McCaughan, Bridgeen; Tang, Sicheng; Fraix, Aurore; Captain, Burjor; Sortino, Salvatore; Callan, John F; Raymo, Françisco M

    2015-09-07

    An amphiphilic polymer with multiple decyl and oligo(ethylene glycol) chains attached to a common poly(methacrylate) backbone assembles into nanoscaled particles in aqueous environments. Hydrophobic anthracene and borondipyrromethene (BODIPY) chromophores can be co-encapsulated within the self-assembling nanoparticles and transported across hydrophilic media. The reversible character of the noncovalent bonds, holding the supramolecular containers together, permits the exchange of their components with fast kinetics in aqueous solution. Incubation of cervical cancer (HeLA) cells with a mixture of two sets of nanoparticles, pre-loaded independently with anthracene or BODIPY chromophores, results in guest scrambling first and then transport of co-entrapped species to the intracellular space. Alternatively, incubation of cells with the two sets of nanocarriers in consecutive steps permits the sequential transport of the anthracene and BODIPY chromophores across the plasma membrane and only then allows their co-encapsulation within the same supramolecular containers. Both mechanisms position the two sets of chromophores with complementary spectral overlap in close proximity to enable the efficient transfer of energy intracellularly from the anthracene donors to the BODIPY acceptors. In the presence of iodine substituents on the BODIPY platform, intersystem crossing follows energy transfer. The resulting triplet state can transfer energy further to molecular oxygen with the concomitant production of singlet oxygen to induce cell mortality. Furthermore, the donor can be excited with two near-infrared photons simultaneously to permit the photoinduced generation of singlet oxygen intracellularly under illumination conditions compatible with applications in vivo. Thus, these supramolecular strategies to control the excitation dynamics of multichromophoric assemblies in the intracellular environment can evolve into valuable protocols for photodynamic therapy.

  15. Modeling of a method of parallel hierarchical transformation for fast recognition of dynamic images

    NASA Astrophysics Data System (ADS)

    Timchenko, Leonid I.; Kokryatskaya, Nataliya I.; Shpakovych, Viktoriya V.

    2013-12-01

    Principles necessary to develop a method and computational facilities for the parallel hierarchical transformation based on high-performance GPUs are discussed in the paper. Mathematic models of the parallel hierarchical (PH) network training for the transformation and a PH network training method for recognition of dynamic images are developed.

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

    SciTech Connect

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

    2016-06-14

    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. Lastly, we demonstrate that by driving the vortex on fast timescales, sequential addressing and coherent manipulation of spins is possible on ~ 100 ns timescales.

  17. Dynamics of the fast component of nano-confined water under electric field

    SciTech Connect

    Omar Diallo, Souleymane; Mamontov, Eugene; Podlesnyak, Andrey A; Ehlers, Georg; Wada, Nobuo; Inagaki, S; Fukushima, Y

    2013-01-01

    We report the diffusion of water molecules confined in the pores of folded silica materials (FSM-12 with average pore diameter of $\\sim$ 16 \\AA), measured by means of quasielastic neutron scattering using the cold neutron chopper spectrometer (CNCS). The goal is to investigate the effect of electric field on the previously observed fast component of nano-confined water. The measurements were taken at temperatures between 220 K and 245 K, and at two electric field values, 0 kV/mm and 2 kV/mm. Similar to the recently observed electric field induced enhancement of the slow translational motion of confined water, there is a an equally important impact of the field on the faster diffusion.

  18. Fast Dynamic Meshing Method Based on Delaunay Graph and Inverse Distance Weighting Interpolation

    NASA Astrophysics Data System (ADS)

    Wang, Yibin; Qin, Ning; Zhao, Ning

    2016-06-01

    A novel mesh deformation technique is developed based on the Delaunay graph mapping method and the inverse distance weighting (IDW) interpolation. The algorithm maintains the advantages of the efficiency of Delaunay-graph-mapping mesh deformation while possess the ability for better controlling the near surface mesh quality. The Delaunay graph is used to divide the mesh domain into a number of sub-domains. On each of the sub-domains, the inverse distance weighting interpolation is applied to build a much smaller sized translation matrix between the original mesh and the deformed mesh, resulting a similar efficiency for the mesh deformation as compared to the fast Delaunay graph mapping method. The paper will show how the near-wall mesh quality is controlled and improved by the new method while the computational time is compared with the original Delaunay graph mapping method.

  19. Hybrid stochastic simulation of reaction-diffusion systems with slow and fast dynamics

    SciTech Connect

    Strehl, Robert; Ilie, Silvana

    2015-12-21

    In this paper, we present a novel hybrid method to simulate discrete stochastic reaction-diffusion models arising in biochemical signaling pathways. We study moderately stiff systems, for which we can partition each reaction or diffusion channel into either a slow or fast subset, based on its propensity. Numerical approaches missing this distinction are often limited with respect to computational run time or approximation quality. We design an approximate scheme that remedies these pitfalls by using a new blending strategy of the well-established inhomogeneous stochastic simulation algorithm and the tau-leaping simulation method. The advantages of our hybrid simulation algorithm are demonstrated on three benchmarking systems, with special focus on approximation accuracy and efficiency.

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

    PubMed Central

    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

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

    DOE PAGES

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

    2016-06-14

    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-vacancymore » spins, resulting in enhanced coherent rotation of the spin state. Lastly, we demonstrate that by driving the vortex on fast timescales, sequential addressing and coherent manipulation of spins is possible on ~ 100 ns timescales.« less

  2. Study of dynamical behaviour of the plasma in a dc non-transferred plasma torch using fast imaging

    NASA Astrophysics Data System (ADS)

    Goyal, Vidhi; Ravi, G.; Bandyopadhyay, P.; Banerjee, S.; Yugesh, V.; Mukherjee, S.

    2017-03-01

    The dynamical behaviour of the plasma in a dc non-transferred plasma torch is the result of complex interactions between various forces acting on the plasma column. We have studied this behaviour in a novel experiment comprising a low power (˜25 kW) torch and fast imaging diagnostics. The nitrogen gas plasma torch was operated at atmospheric pressure for a wide range of gas flow rates (20-60 lpm) and currents (70-120 A). A strong axial external magnetic field (100-500 G) was introduced and end-on images of the plasma column were captured using a high speed camera of frame rate ˜117 000 fps. The studies have yielded dominant role of external magnetic on the arc root dynamics. The column is clearly distinguishable in three main parts: central plasma, cathode-anode junction, and radial component of column that attaches to the anode. The dynamics of the column, especially the angular rotational speed of the radial part of the column, is analyzed in detail in terms of the forces that act upon it. The nature of the arc root attachment is observed to vary with variation in main experimental parameters, such as current, magnetic field, and flow. Arguments are invoked to explain the observed phenomena and a model of the physical processes is presented to explain the phenomena.

  3. Dynamics of fast synaptic excitation during trains of stimulation in myenteric neurons of guinea pig ileum

    PubMed Central

    Ren, Jianhua; Galligan, James J.

    2009-01-01

    Fast excitatory postsynaptic potentials (fEPSPs) occur in bursts in the myenteric plexus during evoked motor reflexes in the guinea-pig ileum in vitro. This study used electrophysiological methods to study fEPSPs during stimulus trains to mimic bursts of synaptic activity in vitro. The amplitude of fEPSPs or fast excitatory postsynaptic currents (EPSCs) declined (rundown) during stimulus trains at frequencies of 0.5, 5, 10 and 20 Hz. At 0.5 Hz, fEPSP or fEPSC amplitude declined by 50% after the first stimulus but remained constant for the remainder of the train. At 5, 10 and 20 Hz, synaptic responses ran down completely with time constants of 0.35, 0.21 and 0.11 s, respectively. Recovery from rundown occurred with a time constant of 7 seconds. Mecamylamine, a nicotinic cholinergic receptor antagonist, or PPADS, a P2X receptor antagonist, reduced fEPSP amplitude, but they had no effect on rundown. Responses caused by trains of ionophoretically-applied ATP or ACh (to mimic fEPSPs or fEPSCs) did not rundown. Blockade of presynaptic inhibitory muscarinic, adenosine A1, opioid, α2-adrenergic and 5-HT1A receptors or pertussis toxin treatment did not alter rundown. Antidromic action potentials followed a 10 Hz stimulus train. Iberiotoxin (100 nM), which was used to block large conductance calcium activated K+ (BK) channels, did not alter rundown. Iberiotoxin increased fEPSP amplitude and action potential duration. These data suggest that synaptic rundown is not due to: a) action potential failure; b) nicotinic or P2X receptor desensitization; c) presynaptic inhibition mediated by pertussis-toxin sensitive G-proteins, or d) BK+ channel activation. Synaptic rundown is likely due to depletion of a readily releasable pool of neurotransmitter. PMID:15664559

  4. Intracellular Parasite Invasion Strategies

    NASA Astrophysics Data System (ADS)

    Sibley, L. D.

    2004-04-01

    Intracellular parasites use various strategies to invade cells and to subvert cellular signaling pathways and, thus, to gain a foothold against host defenses. Efficient cell entry, ability to exploit intracellular niches, and persistence make these parasites treacherous pathogens. Most intracellular parasites gain entry via host-mediated processes, but apicomplexans use a system of adhesion-based motility called ``gliding'' to actively penetrate host cells. Actin polymerization-dependent motility facilitates parasite migration across cellular barriers, enables dissemination within tissues, and powers invasion of host cells. Efficient invasion has brought widespread success to this group, which includes Toxoplasma, Plasmodium, and Cryptosporidium.

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

    NASA Astrophysics Data System (ADS)

    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 30.2 MHz and 28.411 MHz 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 1H are polarized in the magnetic field B0 while fluorine spins 19F 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.

  6. Fast activating voltage- and calcium-dependent potassium (BK) conductance promotes bursting in pituitary cells: a dynamic clamp study

    PubMed Central

    Tabak, Joël; Tomaiuolo, Maurizio; Gonzalez-Iglesias, Arturo E.; Milescu, Lorin S.; Bertram, Richard

    2011-01-01

    The electrical activity pattern of endocrine pituitary cells regulates their basal secretion level. Rat somatotrophs and lactotrophs exhibit spontaneous bursting and have high basal levels of hormone secretion, while gonadotrophs exhibit spontaneous spiking and have low basal hormone secretion. It has been proposed that the difference in electrical activity between bursting somatotrophs and spiking gonadotrophs is due to the presence of large conductance potassium (BK) channels on somatotrophs but not on gonadotrophs. This is one example where the role of an ion channel type may be clearly established. We demonstrate here that BK channels indeed promote bursting activity in pituitary cells. Blocking BK channels in bursting lacto-somatotroph GH4C1 cells changes their firing activity to spiking, while further adding an artificial BK conductance via dynamic clamp restores bursting. Importantly, this burst-promoting effect requires a relatively fast BK activation/deactivation, as predicted by computational models. We also show that adding a fast activating BK conductance to spiking gonadotrophs converts the activity of these cells to bursting. Together, our results suggest that differences in BK channel expression may underlie the differences in electrical activity and basal hormone secretion levels among pituitary cell types and that the rapid rate of BK channel activation is key to its role in burst promotion. PMID:22090511

  7. Analysis of the propagation dynamics and Gouy phase of Airy beams using the fast Fresnel transform algorithm.

    PubMed

    Cottrell, Don M; Davis, Jeffrey A; Berg, Cassidy A; Freeman, Christopher Li

    2014-04-01

    There is great interest in Airy beams because they appear to propagate in a curved path. These beams are usually generated by inserting a cubic phase mask onto the input plane of a Fourier transform system. Here, we utilize a fast Fresnel diffraction algorithm to easily derive both the propagation dynamics and the Gouy phase shift for these beams. The trajectories of these beams can be modified by adding additional linear and quadratic phase terms onto the cubic phase mask. Finally, we have rewritten the equations regarding the propagating Airy beams completely in laboratory coordinates for use by experimentalists. Experimental results are included. We expect that these results will be of great importance in applications of Airy beams.

  8. Tunable nonuniform sampling method for fast calculation and intensity modulation in 3D dynamic holographic display.

    PubMed

    Zhang, Zhao; Liu, Juan; Jia, Jia; Li, Xin; Han, Jian; Hu, Bin; Wang, Yongtian

    2013-08-01

    Heavy computational load of computer-generated hologram (CGH) and imprecise intensity modulation of 3D images are crucial problems in dynamic holographic display. The nonuniform sampling method is proposed to speed up CGH generation and precisely modulate the reconstructed intensities of phase-only CGH. The proposed method can eliminate the redundant information properly, where 70% reduction in the storage amount can be reached when it is combined with the novel lookup table method. Multigrayscale modulation of reconstructed 3D images can be achieved successfully. Numerical simulations and optical experiments are performed, and both are in good agreement. It is believed that the proposed method can be used in 3D dynamic holographic display.

  9. [Effects of NaCl stress on photosynthesis characteristics and fast chlorophyll fluorescence induction dynamics of Pistacia chinensis leaves].

    PubMed

    Li, Xu-Xin; Liu, Bing-Xiang; Guo, Zhi-Tao; Chang, Yue-Xia; He, Lei; Chen, Fang; Lu, Bing-She

    2013-09-01

    By using fast chlorophyll fluorescence induction dynamics analysis technique (JIP-test), this paper studied the photosynthesis characteristics and fast chlorophyll fluorescence induction dynamics of 1-year old Pistacia chinensis seedlings under the stress of NaCl at the concentrations 0% (CK), 0.15%, 0.3%, 0.45%, and 0.6%. With the increasing concentration of NaCl, the contents of Chl a, Chl b, and Chl (a+b) in the seedlings leaves decreased, the Chl a/b ratio decreased after an initial increase, and the carotenoid content increased. The net photosynthetic rate (P(n)) and stomatal conductance (g(s)) decreased gradually with increasing NaCl concentration. The decrease of P(n) was mainly attributed to the stomatal limitation when the NaCl concentration was lower than 0.3%, and to the non-stomatal limitation when the NaCl concentration was higher than 0.3%. The trapped energy flux per RC (TR0/CS0), electron transport flux per RC (ET0/CS0), density of RCs (RC/CS0), and yield or flux ratio (psi(0) or phi(E0)) decreased, but the absorption flux per CS (ABS/CS0) and the K phase (W(k)) and J phase (V) in the O-J-I-P chlorophyll fluorescence induction curves increased distinctly, indicating that NaCl stress damaged the leaf oxygen-evolving complex (OEC), donor sides, and PS II reaction centers. When the NaCl concentration reached 0.3%, the maximum photochemical efficiency (F(v)/F(m)) and performance index (PI(ABS)) decreased 17.7% and 36.6%, respectively, as compared with the control.

  10. Magnetic soft x-ray microscopy-imaging fast spin dynamics inmagnetic nanostructures

    SciTech Connect

    Fischer, Peter; Kim, Dong-Hyun; Mesler, Brooke L.; Chao, Weilun; Sakdinawat, Anne E.; Anderson, Erik H.

    2007-06-01

    Magnetic soft X-ray microscopy combines 15nm spatial resolution with 70ps time resolution and elemental sensitivity. Fresnel zone plates are used as X-ray optics and X-ray magnetic circular dichroism serves as magnetic contrast mechanism. Thus scientifically interesting and technologically relevant low dimensional nanomagnetic systems can be imaged at fundamental length and ultrafast time scales in a unique way. Studies include magnetization reversal in magnetic multilayers, nanopatterned systems, vortex dynamics in nanoelements and spin current induced phenomena.

  11. Measuring fast gene dynamics in single cells with time-lapse luminescence microscopy

    PubMed Central

    Mazo-Vargas, Anyimilehidi; Park, Heungwon; Aydin, Mert; Buchler, Nicolas E.

    2014-01-01

    Time-lapse fluorescence microscopy is an important tool for measuring in vivo gene dynamics in single cells. However, fluorescent proteins are limited by slow chromophore maturation times and the cellular autofluorescence or phototoxicity that arises from light excitation. An alternative is luciferase, an enzyme that emits photons and is active upon folding. The photon flux per luciferase is significantly lower than that for fluorescent proteins. Thus time-lapse luminescence microscopy has been successfully used to track gene dynamics only in larger organisms and for slower processes, for which more total photons can be collected in one exposure. Here we tested green, yellow, and red beetle luciferases and optimized substrate conditions for in vivo luminescence. By combining time-lapse luminescence microscopy with a microfluidic device, we tracked the dynamics of cell cycle genes in single yeast with subminute exposure times over many generations. Our method was faster and in cells with much smaller volumes than previous work. Fluorescence of an optimized reporter (Venus) lagged luminescence by 15–20 min, which is consistent with its known rate of chromophore maturation in yeast. Our work demonstrates that luciferases are better than fluorescent proteins at faithfully tracking the underlying gene expression. PMID:25232010

  12. Fast Atomic-Scale Chemical Imaging of Crystalline Materials and Dynamic Phase Transformations.

    PubMed

    Lu, Ping; Yuan, Ren Liang; Ihlefeld, Jon F; Spoerke, Erik David; Pan, Wei; Zuo, Jian Min

    2016-04-13

    Atomic-scale phenomena fundamentally influence materials form and function that makes the ability to locally probe and study these processes critical to advancing our understanding and development of materials. Atomic-scale chemical imaging by scanning transmission electron microscopy (STEM) using energy-dispersive X-ray spectroscopy (EDS) is a powerful approach to investigate solid crystal structures. Inefficient X-ray emission and collection, however, require long acquisition times (typically hundreds of seconds), making the technique incompatible with electron-beam sensitive materials and study of dynamic material phenomena. Here we describe an atomic-scale STEM-EDS chemical imaging technique that decreases the acquisition time to as little as one second, a reduction of more than 100 times. We demonstrate this new approach using LaAlO3 single crystal and study dynamic phase transformation in beam-sensitive Li[Li0.2Ni0.2Mn0.6]O2 (LNMO) lithium ion battery cathode material. By capturing a series of time-lapsed chemical maps, we show for the first time clear atomic-scale evidence of preferred Ni-mobility in LNMO transformation, revealing new kinetic mechanisms. These examples highlight the potential of this approach toward temporal, atomic-scale mapping of crystal structure and chemistry for investigating dynamic material phenomena.

  13. Fast generation of W states of superconducting qubits with multiple Schrödinger dynamics.

    PubMed

    Kang, Yi-Hao; Chen, Ye-Hong; Wu, Qi-Cheng; Huang, Bi-Hua; Song, Jie; Xia, Yan

    2016-11-09

    In this paper, we present a protocol to generate a W state of three superconducting qubits (SQs) by using multiple Schrödinger dynamics. The three SQs are respective embedded in three different coplanar waveguide resonators (CPWRs), which are coupled to a superconducting coupler (SCC) qubit at the center of the setups. With the multiple Schrödinger dynamics, we build a shortcuts to adiabaticity (STA), which greatly accelerates the evolution of the system. The Rabi frequencies of the laser pulses being designed can be expressed by the superpositions of Gaussian functions via the curves fitting, so that they can be realized easily in experiments. What is more, numerical simulation result shows that the protocol is robust against control parameters variations and decoherence mechanisms, such as the dissipations from the CPWRs and the energy relaxation. In addition, the influences of the dephasing are also resisted on account of the accelerating for the dynamics. Thus, the performance of the protocol is much better than that with the conventional adiabatic passage techniques when the dephasing is taken into account. We hope the protocol could be implemented easily in experiments with current technology.

  14. Fast generation of W states of superconducting qubits with multiple Schrödinger dynamics

    PubMed Central

    Kang, Yi-Hao; Chen, Ye-Hong; Wu, Qi-Cheng; Huang, Bi-Hua; Song, Jie; Xia, Yan

    2016-01-01

    In this paper, we present a protocol to generate a W state of three superconducting qubits (SQs) by using multiple Schrödinger dynamics. The three SQs are respective embedded in three different coplanar waveguide resonators (CPWRs), which are coupled to a superconducting coupler (SCC) qubit at the center of the setups. With the multiple Schrödinger dynamics, we build a shortcuts to adiabaticity (STA), which greatly accelerates the evolution of the system. The Rabi frequencies of the laser pulses being designed can be expressed by the superpositions of Gaussian functions via the curves fitting, so that they can be realized easily in experiments. What is more, numerical simulation result shows that the protocol is robust against control parameters variations and decoherence mechanisms, such as the dissipations from the CPWRs and the energy relaxation. In addition, the influences of the dephasing are also resisted on account of the accelerating for the dynamics. Thus, the performance of the protocol is much better than that with the conventional adiabatic passage techniques when the dephasing is taken into account. We hope the protocol could be implemented easily in experiments with current technology. PMID:27827422

  15. ADAHELI: exploring the fast, dynamic Sun in the x-ray, optical, and near-infrared

    NASA Astrophysics Data System (ADS)

    Berrilli, Francesco; Soffitta, Paolo; Velli, Marco; Sabatini, Paolo; Bigazzi, Alberto; Bellazzini, Ronaldo; Bellot Rubio, Luis Ramon; Brez, Alessandro; Carbone, Vincenzo; Cauzzi, Gianna; Cavallini, Fabio; Consolini, Giuseppe; Curti, Fabio; Del Moro, Dario; Di Giorgio, Anna Maria; Ermolli, Ilaria; Fabiani, Sergio; Faurobert, Marianne; Feller, Alex; Galsgaard, Klaus; Gburek, Szymon; Giannattasio, Fabio; Giovannelli, Luca; Hirzberger, Johann; Jefferies, Stuart M.; Madjarska, Maria S.; Manni, Fabio; Mazzoni, Alessandro; Muleri, Fabio; Penza, Valentina; Peres, Giovanni; Piazzesi, Roberto; Pieralli, Francesca; Pietropaolo, Ermanno; Pillet, Valentin Martinez; Pinchera, Michele; Reale, Fabio; Romano, Paolo; Romoli, Andrea; Romoli, Marco; Rubini, Alda; Rudawy, Pawel; Sandri, Paolo; Scardigli, Stefano; Spandre, Gloria; Solanki, Sami K.; Stangalini, Marco; Vecchio, Antonio; Zuccarello, Francesca

    2015-10-01

    Advanced Astronomy for Heliophysics Plus (ADAHELI) is a project concept for a small solar and space weather mission with a budget compatible with an European Space Agency (ESA) S-class mission, including launch, and a fast development cycle. ADAHELI was submitted to the European Space Agency by a European-wide consortium of solar physics research institutes in response to the "Call for a small mission opportunity for a launch in 2017," of March 9, 2012. The ADAHELI project builds on the heritage of the former ADAHELI mission, which had successfully completed its phase-A study under the Italian Space Agency 2007 Small Mission Programme, thus proving the soundness and feasibility of its innovative low-budget design. ADAHELI is a solar space mission with two main instruments: ISODY: an imager, based on Fabry-Pérot interferometers, whose design is optimized to the acquisition of highest cadence, long-duration, multiline spectropolarimetric images in the visible/near-infrared region of the solar spectrum. XSPO: an x-ray polarimeter for solar flares in x-rays with energies in the 15 to 35 keV range. ADAHELI is capable of performing observations that cannot be addressed by other currently planned solar space missions, due to their limited telemetry, or by ground-based facilities, due to the problematic effect of the terrestrial atmosphere.

  16. Fast and Slow Dynamics in a Discotic Liquid Crystal with Regions of Columnar Order and Disorder

    NASA Astrophysics Data System (ADS)

    Hansen, M. R.; Feng, X.; Macho, V.; Müllen, K.; Spiess, H. W.; Floudas, G.

    2011-12-01

    Aromatic disk-shaped molecules tend to self-organize into a herringbone packing where the disks are inclined at angles ±θ with respect to the axis of the column. In discotic liquid crystals this can introduce defects between stacks of limited length. In a C3-symmetric hexa-peri-hexabenzocoronene, solid-state NMR, x-ray scattering, and rheology identifies such a packing with θ=43° and stacks of about seven disks. Disordered regions containing defects fill the space in between the ordered stacks. Biaxial intra- and intercolumnar dynamics differing by eight decades are identified.

  17. Fast and slow dynamics in a discotic liquid crystal with regions of columnar order and disorder.

    PubMed

    Hansen, M R; Feng, X; Macho, V; Müllen, K; Spiess, H W; Floudas, G

    2011-12-16

    Aromatic disk-shaped molecules tend to self-organize into a herringbone packing where the disks are inclined at angles ±θ with respect to the axis of the column. In discotic liquid crystals this can introduce defects between stacks of limited length. In a C(3)-symmetric hexa-peri-hexabenzocoronene, solid-state NMR, x-ray scattering, and rheology identifies such a packing with θ=43° and stacks of about seven disks. Disordered regions containing defects fill the space in between the ordered stacks. Biaxial intra- and intercolumnar dynamics differing by eight decades are identified.

  18. Design and testing of magnetorheological valve with fast force response time and great dynamic force range

    NASA Astrophysics Data System (ADS)

    Kubík, M.; Macháček, O.; Strecker, Z.; Roupec, J.; Mazůrek, I.

    2017-04-01

    The paper deals with design, simulation and experimental testing of a magnetorheological (MR) valve with short response time. The short response time is achieved by a suitable design of an active zone in combination with use of a ferrite material for magnetic circuit. The magneto-static model and the simplified hydraulic model of the MR valve are examined and experimentally verified. The development the MR valve achieves an average response time 4.1 ms and the maximum dynamic force range of eight.

  19. Large dynamic light-matter entanglement from driving neither too fast nor too slow

    NASA Astrophysics Data System (ADS)

    Acevedo, O. L.; Quiroga, L.; Rodríguez, F. J.; Johnson, N. F.

    2015-09-01

    A significant problem facing next-generation quantum technologies is how to generate and manipulate macroscopic entanglement in light and matter systems. Here we report a regime of dynamical light-matter behavior in which a giant, system-wide entanglement is generated by varying the light-matter coupling at intermediate velocities. This enhancement is far larger, broader ranged, and more experimentally accessible than that occurring near the quantum phase transition of the same model under adiabatic conditions. By appropriate choices of the coupling within this intermediate regime, the enhanced entanglement can be made to spread system-wide or to reside in each subsystem separately.

  20. Fast optical cooling of nanomechanical cantilever with the dynamical Zeeman effect.

    PubMed

    Zhang, Jian-Qi; Zhang, Shuo; Zou, Jin-Hua; Chen, Liang; Yang, Wen; Li, Yong; Feng, Mang

    2013-12-02

    We propose an efficient optical electromagnetically induced transparency (EIT) cooling scheme for a cantilever with a nitrogen-vacancy center attached in a non-uniform magnetic field using dynamical Zeeman effect. In our scheme, the Zeeman effect combined with the quantum interference effect enhances the desired cooling transition and suppresses the undesired heating transitions. As a result, the cantilever can be cooled down to nearly the vibrational ground state under realistic experimental conditions within a short time. This efficient optical EIT cooling scheme can be reduced to the typical EIT cooling scheme under special conditions.

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

    NASA Astrophysics Data System (ADS)

    Han, Wang; Maomao, Sun

    2014-04-01

    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 IQ 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.

  2. Pharmaceutical evaluation and dynamic vapor sorption studies of fast dissolving intraoral films of Loratadine.

    PubMed

    Arya, Arun; Sharma, Vijay; Pathak, Kamla

    2013-01-01

    The aim of the study was to develop intraoral films (IOFs) of loratadine and to assess the storage conditions by dynamic vapour sorption studies. The excipient selection was guided by drug excipient compatibility studies and the incompatibility of loratadine with dibutylphathalate and Tween20 was confirmed by Electro-spray Ionization Mass Spectrometry. Thus intaroral films were developed using HPMC E-15 LV and polyvinyl alcohol (PVA) as lone and mixed film formers to get eighteen formulations (F1- F18) that varied in the type and amount of plasticizer used. Four formulations selected on the basis of pharmacotechnical characteristics were improvised by inclusion of Poloxamer407 that lowered the dissolving time to the tune of 36-55%. Dynamic vapour sorption studies of the improvised films (PF1-PF4) demonstrated an increase of 2% by weight at 50% relative humidity (RH) and 25°C suggesting storage of the films below the stated conditions. In vitro drug release studies in phosphate buffer pH 6.8 demonstrated more than 94% cumulative drug release from the formulations. Analysis of model independent parameters identified PF2 as the best formulation that was nine times superior in its dissolution efficiency to Lorafast tablets(®).

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

    NASA Technical Reports Server (NTRS)

    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.

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

    NASA Astrophysics Data System (ADS)

    Wu, Xia; Cheng, Wen

    2014-09-01

    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.

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

    PubMed

    Wu, Xia; Cheng, Wen

    2014-09-28

    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.

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

    SciTech Connect

    Wu, Xia Cheng, Wen

    2014-09-28

    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){sub 79} clusters with DFT-fit parameters of Gupta potential.

  7. AWE-WQ: Fast-Forwarding Molecular Dynamics Using the Accelerated Weighted Ensemble

    PubMed Central

    2015-01-01

    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. PMID:25207854

  8. Dynamic UltraFast 2D EXchange SpectroscopY (UF-EXSY) of hyperpolarized substrates

    PubMed Central

    Swisher, Christine Leon; Koelsch, Bertram; Sukumar, Subramianam; Sriram, Renuka; Santos, Romelyn Delos; Wang, Zhen Jane; Kurhanewicz, John; Vigneron, Daniel; Larson, Peder

    2015-01-01

    In this work, we present a new ultrafast method for acquiring dynamic 2D EXchange SpectroscopY (EXSY) within a single acquisition. This technique reconstructs two-dimensional EXSY spectra from one-dimensional spectra based on the phase accrual during echo times. The Ultrafast-EXSY acquisition overcomes long acquisition times typically needed to acquire 2D NMR data by utilizing sparsity and phase dependence to dramatically undersample in the indirect time dimension. This allows for the acquisition of the 2D spectrum within a single shot. We have validated this method in simulations and hyperpolarized enzyme assay experiments separating the dehydration of pyruvate and lactate-to-pyruvate conversion. In a renal cell carcinoma cell (RCC) line, bidirectional exchange was observed. This new technique revealed decreased conversion of lactate-to-pyruvate with high expression of monocarboxylate transporter 4 (MCT4), known to correlate with aggressive cancer phenotypes. We also showed feasibility of this technique in vivo in a RCC model where bidirectional exchange was observed for pyruvate–lactate, pyruvate–alanine, and pyruvate–hydrate and were resolved in time. Broadly, the technique is well suited to investigate the dynamics of multiple exchange pathways and applicable to hyperpolarized substrates where chemical exchange has shown great promise across a range of disciplines. PMID:26117655

  9. Dynamic UltraFast 2D EXchange SpectroscopY (UF-EXSY) of hyperpolarized substrates

    NASA Astrophysics Data System (ADS)

    Leon Swisher, Christine; Koelsch, Bertram; Sukumar, Subramianam; Sriram, Renuka; Santos, Romelyn Delos; Wang, Zhen Jane; Kurhanewicz, John; Vigneron, Daniel; Larson, Peder

    2015-08-01

    In this work, we present a new ultrafast method for acquiring dynamic 2D EXchange SpectroscopY (EXSY) within a single acquisition. This technique reconstructs two-dimensional EXSY spectra from one-dimensional spectra based on the phase accrual during echo times. The Ultrafast-EXSY acquisition overcomes long acquisition times typically needed to acquire 2D NMR data by utilizing sparsity and phase dependence to dramatically undersample in the indirect time dimension. This allows for the acquisition of the 2D spectrum within a single shot. We have validated this method in simulations and hyperpolarized enzyme assay experiments separating the dehydration of pyruvate and lactate-to-pyruvate conversion. In a renal cell carcinoma cell (RCC) line, bidirectional exchange was observed. This new technique revealed decreased conversion of lactate-to-pyruvate with high expression of monocarboxylate transporter 4 (MCT4), known to correlate with aggressive cancer phenotypes. We also showed feasibility of this technique in vivo in a RCC model where bidirectional exchange was observed for pyruvate-lactate, pyruvate-alanine, and pyruvate-hydrate and were resolved in time. Broadly, the technique is well suited to investigate the dynamics of multiple exchange pathways and applicable to hyperpolarized substrates where chemical exchange has shown great promise across a range of disciplines.

  10. Evaluation of nonlinear structural dynamic responses using a fast-running spring-mass formulation

    NASA Astrophysics Data System (ADS)

    Benjamin, A. S.; Altman, B. S.; Gruda, J. D.

    In today's world, accurate finite-element simulations of large nonlinear systems may require meshes composed of hundreds of thousands of degrees of freedom. Even with today's fast computers and the promise of ever-faster ones in the future, central processing unit (CPU) expenditures for such problems could be measured in days. Many contemporary engineering problems, such as those found in risk assessment, probabilistic structural analysis, and structural design optimization, cannot tolerate the cost or turnaround time for such CPU-intensive analyses, because these applications require a large number of cases to be run with different inputs. For many risk assessment applications, analysts would prefer running times to be measurable in minutes. There is therefore a need for approximation methods which can solve such problems far more efficiently than the very detailed methods and yet maintain an acceptable degree of accuracy. For this purpose, we have been working on two methods of approximation: neural networks and spring-mass models. This paper presents our work and results to date for spring-mass modeling and analysis, since we are further along in this area than in the neural network formulation. It describes the physical and numerical models contained in a code we developed called STRESS, which stands for 'Spring-mass Transient Response Evaluation for structural Systems'. The paper also presents results for a demonstration problem, and compares these with results obtained for the same problem using PRONTO3D, a state-of-the-art finite element code which was also developed at Sandia.

  11. Evaluation of nonlinear structural dynamic responses using a fast-running spring-mass formulation

    SciTech Connect

    Benjamin, A.S.; Altman, B.S.; Gruda, J.D.

    1995-03-01

    In today`s world, accurate finite-element simulations of large nonlinear systems may require meshes composed of hundreds of thousands of degrees of freedom. Even with today`s fast computers and the promise of ever-faster ones in the future, central processing unit (CPU) expenditures for such problems could be measured in days. Many contemporary engineering problems, such as those found in risk assessment, probabilistic structural analysis, and structural design optimization, cannot tolerate the cost or turnaround time for such CPU-intensive analyses, because these applications require a large number of cases to be run with different inputs. For many risk assessment applications, analysts would prefer running times to be measurable in minutes. There is therefore a need for approximation methods which can solve such problems far more efficiently than the very detailed methods and yet maintain an acceptable degree of accuracy. For this purpose, we have been working on two methods of approximation: neural networks and spring-mass models. This paper presents our work and results to date for spring-mass modeling and analysis, since we are further along in this area than in the neural network formulation. It describes the physical and numerical models contained in a code we developed called STRESS, which stands for ``Spring-mass Transient Response Evaluation for structural Systems``. The paper also presents results for a demonstration problem, and compares these with results obtained for the same problem using PRONTO3D, a state-of-the-art finite element code which was also developed at Sandia.

  12. Hamilton-Jacobi equation for the least-action/least-time dynamical path based on fast marching method

    NASA Astrophysics Data System (ADS)

    Dey, Bijoy K.; Janicki, Marek R.; Ayers, Paul W.

    2004-10-01

    Classical dynamics can be described with Newton's equation of motion or, totally equivalently, using the Hamilton-Jacobi equation. Here, the possibility of using the Hamilton-Jacobi equation to describe chemical reaction dynamics is explored. This requires an efficient computational approach for constructing the physically and chemically relevant solutions to the Hamilton-Jacobi equation; here we solve Hamilton-Jacobi equations on a Cartesian grid using Sethian's fast marching method [J. A. Sethian, Proc. Natl. Acad. Sci. USA 93, 1591 (1996)]. Using this method, we can—starting from an arbitrary initial conformation—find reaction paths that minimize the action or the time. The method is demonstrated by computing the mechanism for two different systems: a model system with four different stationary configurations and the H+H2→H2+H reaction. Least-time paths (termed brachistochrones in classical mechanics) seem to be a suitable chioce for the reaction coordinate, allowing one to determine the key intermediates and final product of a chemical reaction. For conservative systems the Hamilton-Jacobi equation does not depend on the time, so this approach may be useful for simulating systems where important motions occur on a variety of different time scales.

  13. Dynamic compressed HRRP generation for random stepped-frequency radar based on complex-valued fast sequential homotopy.

    PubMed

    You, Peng; Liu, Zhen; Wang, Hongqiang; Wei, Xizhang; Li, Xiang

    2014-05-08

    Compressed sensing has been applied to achieve high resolution range profiles (HRRPs) using a stepped-frequency radar. In this new scheme, much fewer pulses are required to recover the target's strong scattering centers, which can greatly reduce the coherent processing interval (CPI) and improve the anti-jamming capability. For practical applications, however, the required number of pulses is difficult to determine in advance and any reduction of the transmitted pulses is attractive. In this paper, a dynamic compressed sensing strategy for HRRP generation is proposed, in which the estimated HRRP is updated with sequentially transmitted and received pulses until the proper stopping rules are satisfied. To efficiently implement the sequential update, a complex-valued fast sequential homotopy (CV-FSH) algorithm is developed based on group sparse recovery. This algorithm performs as an efficient recursive procedure of sparse recovery, thus avoiding solving a new optimization problem from scratch. Furthermore, the proper stopping rules are presented according to the special characteristics of HRRP. Therefore, the optimal number of pulses required in each CPI can be sought adapting to the echo signal. The results using simulated and real data show the effectiveness of the proposed approach and demonstrate that the established dynamic strategy is more suitable for uncooperative targets.

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

    PubMed

    Zhang, Dashan; Guo, Jie; Lei, Xiujun; Zhu, Changan

    2016-04-22

    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.

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:26907291

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

    PubMed Central

    Zhang, Dashan; Guo, Jie; Lei, Xiujun; Zhu, Changan

    2016-01-01

    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. PMID:27110784

  18. Nonlinear dynamics of 3D beams of fast magnetosonic waves propagating in the ionospheric and magnetospheric plasma

    NASA Astrophysics Data System (ADS)

    Belashov, V. Yu.; Belashova, E. S.

    2016-11-01

    On the basis of the model of the three-dimensional (3D) generalized Kadomtsev-Petviashvili equation for magnetic field h = B / B the formation, stability, and dynamics of 3D soliton-like structures, such as the beams of fast magnetosonic (FMS) waves generated in ionospheric and magnetospheric plasma at a low-frequency branch of oscillations when β = 4 πnT/ B 2 ≪ 1 and β > 1, are studied. The study takes into account the highest dispersion correction determined by values of the plasma parameters and the angle θ = ( B, k), which plays a key role in the FMS beam propagation at those angles to the magnetic field that are close to π/2. The stability of multidimensional solutions is studied by an investigation of the Hamiltonian boundness under its deformations on the basis of solving of the corresponding variational problem. The evolution and dynamics of the 3D FMS wave beam are studied by the numerical integration of equations with the use of specially developed methods. The results can be interpreted in terms of the self-focusing phenomenon, as the formation of a stationary beam and the scattering and self-focusing of the solitary beam of FMS waves. These cases were studied with a detailed investigation of all evolutionary stages of the 3D FMS wave beams in the ionospheric and magnetospheric plasma.

  19. Dynamic Compressed HRRP Generation for Random Stepped-Frequency Radar Based on Complex-Valued Fast Sequential Homotopy

    PubMed Central

    You, Peng; Liu, Zhen; Wang, Hongqiang; Wei, Xizhang; Li, Xiang

    2014-01-01

    Compressed sensing has been applied to achieve high resolution range profiles (HRRPs) using a stepped-frequency radar. In this new scheme, much fewer pulses are required to recover the target's strong scattering centers, which can greatly reduce the coherent processing interval (CPI) and improve the anti-jamming capability. For practical applications, however, the required number of pulses is difficult to determine in advance and any reduction of the transmitted pulses is attractive. In this paper, a dynamic compressed sensing strategy for HRRP generation is proposed, in which the estimated HRRP is updated with sequentially transmitted and received pulses until the proper stopping rules are satisfied. To efficiently implement the sequential update, a complex-valued fast sequential homotopy (CV-FSH) algorithm is developed based on group sparse recovery. This algorithm performs as an efficient recursive procedure of sparse recovery, thus avoiding solving a new optimization problem from scratch. Furthermore, the proper stopping rules are presented according to the special characteristics of HRRP. Therefore, the optimal number of pulses required in each CPI can be sought adapting to the echo signal. The results using simulated and real data show the effectiveness of the proposed approach and demonstrate that the established dynamic strategy is more suitable for uncooperative targets. PMID:24815679

  20. Measuring fast stochastic displacements of bio-membranes with dynamic optical displacement spectroscopy.

    PubMed

    Monzel, C; Schmidt, D; Kleusch, C; Kirchenbüchler, D; Seifert, U; Smith, A-S; Sengupta, K; Merkel, R

    2015-10-06

    Stochastic displacements or fluctuations of biological membranes are increasingly recognized as an important aspect of many physiological processes, but hitherto their precise quantification in living cells was limited due to a lack of tools to accurately record them. Here we introduce a novel technique--dynamic optical displacement spectroscopy (DODS), to measure stochastic displacements of membranes with unprecedented combined spatiotemporal resolution of 20 nm and 10 μs. The technique was validated by measuring bending fluctuations of model membranes. DODS was then used to explore the fluctuations in human red blood cells, which showed an ATP-induced enhancement of non-Gaussian behaviour. Plasma membrane fluctuations of human macrophages were quantified to this accuracy for the first time. Stimulation with a cytokine enhanced non-Gaussian contributions to these fluctuations. Simplicity of implementation, and high accuracy make DODS a promising tool for comprehensive understanding of stochastic membrane processes.

  1. Fast dynamic holographic recording based on conductive ionic metal-alkanoate liquid crystals and smectic glasses.

    PubMed

    Klimusheva, G; Bugaychuk, S; Garbovskiy, Yu; Kolesnyk, O; Mirnaya, T; Ishchenko, A

    2006-01-15

    Recordings of dynamic holograms with microsecond relaxation times under the action of nanosecond laser pulses are obtained in composites on the base of a novel class of liquid crystals (LCs) in ionic metal-alkanoates. Holographic parameters and relaxation characteristics are measured for doped lyotropic ionic LC, for sandwichlike cells (consisting of a dye layer and a layer of the lyotropic ionic LC), and for colored ionic smectic glasses. The structure of the materials is investigated by use of the small-angle x-ray technique. The mechanism of resonance nonlinearity in photosensitive centers and mechanisms of the grating erasure connected with a charge transport in the ionic conductive LC matrix are discussed.

  2. Fast direct reconstruction strategy of dynamic fluorescence molecular tomography using graphics processing units

    NASA Astrophysics Data System (ADS)

    Chen, Maomao; Zhang, Jiulou; Cai, Chuangjian; Gao, Yang; Luo, Jianwen

    2016-06-01

    Dynamic fluorescence molecular tomography (DFMT) is a valuable method to evaluate the metabolic process of contrast agents in different organs in vivo, and direct reconstruction methods can improve the temporal resolution of DFMT. However, challenges still remain due to the large time consumption of the direct reconstruction methods. An acceleration strategy using graphics processing units (GPU) is presented. The procedure of conjugate gradient optimization in the direct reconstruction method is programmed using the compute unified device architecture and then accelerated on GPU. Numerical simulations and in vivo experiments are performed to validate the feasibility of the strategy. The results demonstrate that, compared with the traditional method, the proposed strategy can reduce the time consumption by ˜90% without a degradation of quality.

  3. A fast parallel Poisson solver on irregular domains applied to beam dynamics simulations

    SciTech Connect

    Adelmann, A. Arbenz, P. Ineichen, Y.

    2010-06-20

    We discuss the scalable parallel solution of the Poisson equation within a Particle-In-Cell (PIC) code for the simulation of electron beams in particle accelerators of irregular shape. The problem is discretized by Finite Differences. Depending on the treatment of the Dirichlet boundary the resulting system of equations is symmetric or 'mildly' nonsymmetric positive definite. In all cases, the system is solved by the preconditioned conjugate gradient algorithm with smoothed aggregation (SA) based algebraic multigrid (AMG) preconditioning. We investigate variants of the implementation of SA-AMG that lead to considerable improvements in the execution times. We demonstrate good scalability of the solver on distributed memory parallel processor with up to 2048 processors. We also compare our iterative solver with an FFT-based solver that is more commonly used for applications in beam dynamics.

  4. Measuring fast stochastic displacements of bio-membranes with dynamic optical displacement spectroscopy

    NASA Astrophysics Data System (ADS)

    Monzel, C.; Schmidt, D.; Kleusch, C.; Kirchenbüchler, D.; Seifert, U.; Smith, A.-S.; Sengupta, K.; Merkel, R.

    2015-10-01

    Stochastic displacements or fluctuations of biological membranes are increasingly recognized as an important aspect of many physiological processes, but hitherto their precise quantification in living cells was limited due to a lack of tools to accurately record them. Here we introduce a novel technique--dynamic optical displacement spectroscopy (DODS), to measure stochastic displacements of membranes with unprecedented combined spatiotemporal resolution of 20 nm and 10 μs. The technique was validated by measuring bending fluctuations of model membranes. DODS was then used to explore the fluctuations in human red blood cells, which showed an ATP-induced enhancement of non-Gaussian behaviour. Plasma membrane fluctuations of human macrophages were quantified to this accuracy for the first time. Stimulation with a cytokine enhanced non-Gaussian contributions to these fluctuations. Simplicity of implementation, and high accuracy make DODS a promising tool for comprehensive understanding of stochastic membrane processes.

  5. Fast Pairwise Structural RNA Alignments by Pruning of the Dynamical Programming Matrix

    PubMed Central

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

    2007-01-01

    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. PMID:17937495

  6. Fast recovery of free energy landscapes via diffusion-map-directed molecular dynamics.

    PubMed

    Preto, Jordane; Clementi, Cecilia

    2014-09-28

    The reaction pathways characterizing macromolecular systems of biological interest are associated with high free energy barriers. Resorting to the standard all-atom molecular dynamics (MD) to explore such critical regions may be inappropriate as the time needed to observe the relevant transitions can be remarkably long. In this paper, we present a new method called Extended Diffusion-Map-directed Molecular Dynamics (extended DM-d-MD) used to enhance the sampling of MD trajectories in such a way as to rapidly cover all important regions of the free energy landscape including deep metastable states and critical transition paths. Moreover, extended DM-d-MD was combined with a reweighting scheme enabling to save on-the-fly information about the Boltzmann distribution. Our algorithm was successfully applied to two systems, alanine dipeptide and alanine-12. Due to the enhanced sampling, the Boltzmann distribution is recovered much faster than in plain MD simulations. For alanine dipeptide, we report a speedup of one order of magnitude with respect to plain MD simulations. For alanine-12, our algorithm allows us to highlight all important unfolded basins in several days of computation when one single misfolded event is barely observable within the same amount of computational time by plain MD simulations. Our method is reaction coordinate free, shows little dependence on the a priori knowledge of the system, and can be implemented in such a way that the biased steps are not computationally expensive with respect to MD simulations thus making our approach well adapted for larger complex systems from which little information is known.

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

    NASA Astrophysics Data System (ADS)

    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

  8. Investigation of a FAST-OrcaFlex Coupling Module for Integrating Turbine and Mooring Dynamics of Offshore Floating Wind Turbines: Preprint

    SciTech Connect

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

    2011-10-01

    To enable offshore floating wind turbine design, the following are required: accurate modeling of the wind turbine structural dynamics, aerodynamics, platform hydrodynamics, a mooring system, and control algorithms. Mooring and anchor design can appreciably affect the dynamic response of offshore wind platforms that are subject to environmental loads. From an engineering perspective, system behavior and line loads must be studied well to ensure the overall design is fit for the intended purpose. FAST (Fatigue, Aerodynamics, Structures and Turbulence) is a comprehensive simulation tool used for modeling land-based and offshore wind turbines. In the case of a floating turbine, continuous cable theory is used to emulate mooring line dynamics. Higher modeling fidelity can be gained through the use of finite element mooring theory. This can be achieved through the FASTlink coupling module, which couples FAST with OrcaFlex, a commercial simulation tool used for modeling mooring line dynamics. In this application, FAST is responsible for capturing the aerodynamic loads and flexure of the wind turbine and its tower, and OrcaFlex models the mooring line and hydrodynamic effects below the water surface. This paper investigates the accuracy and stability of the FAST/OrcaFlex coupling operation.

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

    PubMed

    van de Kerk, Madelon; de Kroon, Hans; Conde, Dalia A; Jongejans, Eelke

    2013-01-01

    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.

  10. Carnivora Population Dynamics Are as Slow and as Fast as Those of Other Mammals: Implications for Their Conservation

    PubMed Central

    van de Kerk, Madelon; de Kroon, Hans; Conde, Dalia A.; Jongejans, Eelke

    2013-01-01

    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. PMID:23950922

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

    NASA Astrophysics Data System (ADS)

    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.

  12. Strong-field isomerization dynamics of fast beams of hydrocarbon ions

    NASA Astrophysics Data System (ADS)

    Jochim, Bethany; Rajput, Jyoti; Berry, Ben; Severt, T.; Zohrabi, M.; Feizollah, Peyman; Carnes, K. D.; Esry, B. D.; Ben-Itzhak, I.

    2016-05-01

    Bond rearrangement and fragmentation of hydrocarbons in intense laser fields has been a topic of considerable interest in the strong-field community in recent years. We study the interactions of keV hydrocarbon ion beams with ultrafast, intense laser pulses, employing coincidence 3D momentum imaging to elucidate the fragmentation dynamics and identify laser parameters that might be used for controlling outcomes such as the branching ratios. We focus on dissociation to ensure that isomerization occurs on the particular electronic channels of the molecular ion investigated. In C2 H2+, for example, we measure the intensity-dependent branching ratios of the acetylene (CH++CH) and vinylidene (e . g . , C++ CH2) channels. The relative fragmentation rates between the acetylene and vinylidene channels change by a factor of ~ 2 over the range of experimental intensities (1013- 1015 W/ cm2). Other hydrocarbons of interest include not only cations but also anions, such as C2 H 2 -. Supported by the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U. S. Department of Energy. BJ was also supported in part by DOE-SCGF (DE-AC05-06OR23100).

  13. Dynamic light scattering: A fast and reliable method to analyze bacterial growth during the lag phase.

    PubMed

    Vargas, Susana; Millán-Chiu, Blanca E; Arvizu-Medrano, Sofía M; Loske, Achim M; Rodríguez, Rogelio

    2017-04-09

    A comparison between plate counting (PC) and dynamic light scattering (DLS) is reported. PC is the standard technique to determine bacterial population as a function of time; however, this method has drawbacks, such as the cumbersome preparation and handling of samples, as well as the long time required to obtain results. Alternative methods based on optical density are faster, but do not distinguish viable from non-viable cells. These inconveniences are overcome by using DLS. Two different bacteria strains were considered: Escherichia coli and Staphylococcus aureus. DLS was performed at two different illuminating conditions: continuous and intermittent. By the increment of particle size as a function of time, it was possible to observe cell division and the formation of aggregates containing very few bacteria. The scattered intensity profiles showed the lag phase and the transition to the exponential phase of growth, providing a quantity proportional to viable bacteria concentration. The results revealed a clear and linear correlation in both lag and exponential phase, between the Log10(colony-forming units/mL) from PC and the Log10 of the scattered intensity Is from DLS. These correlations provide a good support to use DLS as an alternative technique to determine bacterial population.

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

    PubMed Central

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

    2013-01-01

    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. PMID:23822346

  15. Dynamic time warping in phoneme modeling for fast pronunciation error detection.

    PubMed

    Miodonska, Zuzanna; Bugdol, Marcin D; Krecichwost, Michal

    2016-02-01

    The presented paper describes a novel approach to the detection of pronunciation errors. It makes use of the modeling of well-pronounced and mispronounced phonemes by means of the Dynamic Time Warping (DTW) algorithm. Four approaches that make use of the DTW phoneme modeling were developed to detect pronunciation errors: Variations of the Word Structure (VoWS), Normalized Phoneme Distances Thresholding (NPDT), Furthest Segment Search (FSS) and Normalized Furthest Segment Search (NFSS). The performance evaluation of each module was carried out using a speech database of correctly and incorrectly pronounced words in the Polish language, with up to 10 patterns of every trained word from a set of 12 words having different phonetic structures. The performance of DTW modeling was compared to Hidden Markov Models (HMM) that were used for the same four approaches (VoWS, NPDT, FSS, NFSS). The average error rate (AER) was the lowest for DTW with NPDT (AER=0.287) and scored better than HMM with FSS (AER=0.473), which was the best result for HMM. The DTW modeling was faster than HMM for all four approaches. This technique can be used for computer-assisted pronunciation training systems that can work with a relatively small training speech corpus (less than 20 patterns per word) to support speech therapy at home.

  16. Fast packet switching algorithms for dynamic resource control over ATM networks

    SciTech Connect

    Tsang, R.P.; Keattihananant, P.; Chang, T.; Heieh, J.; Du, D.

    1996-12-01

    Real-time continuous media traffic, such as digital video and audio, is expected to comprise a large percentage of the network load on future high speed packet switch networks such as ATM. A major feature which distinguishes high speed networks from traditional slower speed networks is the large amount of data the network must process very quickly. For efficient network usage, traffic control mechanisms are essential. Currently, most mechanisms for traffic control (such as flow control) have centered on the support of Available Bit Rate (ABR), i.e., non real-time, traffic. With regard to ATM, for ABR traffic, two major types of schemes which have been proposed are rate- control and credit-control schemes. Neither of these schemes are directly applicable to Real-time Variable Bit Rate (VBR) traffic such as continuous media traffic. Traffic control for continuous media traffic is an inherently difficult problem due to the time- sensitive nature of the traffic and its unpredictable burstiness. In this study, we present a scheme which controls traffic by dynamically allocating/de- allocating resources among competing VCs based upon their real-time requirements. This scheme incorporates a form of rate- control, real-time burst-level scheduling and link-link flow control. We show analytically potential performance improvements of our rate- control scheme and present a scheme for buffer dimensioning. We also present simulation results of our schemes and discuss the tradeoffs inherent in maintaining high network utilization and statistically guaranteeing many users` Quality of Service.

  17. Ultra-Fast Excited State Dynamics in Green Fluorescent Protein: Multiple States and Proton Transfer

    NASA Astrophysics Data System (ADS)

    Chattoraj, Mita; King, Brett A.; Bublitz, Gerold U.; Boxer, Steven G.

    1996-08-01

    The green fluorescent protein (GFP) of the jellyfish Aequorea Victoria has attracted widespread interest since the discovery that its chromophore is generated by the autocatalytic, posttranslational cyclization and oxidation of a hexapeptide unit. This permits fusion of the DNA sequence of GFP with that of any protein whose expression or transport can then be readily monitored by sensitive fluorescence methods without the need to add exogenous fluorescent dyes. The excited state dynamics of GFP were studied following photo-excitation of each of its two strong absorption bands in the visible using fluorescence upconversion spectroscopy (about 100 fs time resolution). It is shown that excitation of the higher energy feature leads very rapidly to a form of the lower energy species, and that the excited state interconversion rate can be markedly slowed by replacing exchangeable protons with deuterons. This observation and others lead to a model in which the two visible absorption bands correspond to GFP in two ground-state conformations. These conformations can be slowly interconverted in the ground state, but the process is much faster in the excited state. The observed isotope effect suggests that the initial excited state process involves a proton transfer reaction that is followed by additional structural changes. These observations may help to rationalize and motivate mutations that alter the absorption properties and improve the photo stability of GFP.

  18. Fast and cheap prototyping of nonstandard optical components for sensing speckle dynamics

    NASA Astrophysics Data System (ADS)

    Jakobsen, M. L.; Olesen, A. S.; Stubager, J.; Hanson, S. G.; Kühn, Jan; Pedersen, H. C.

    2016-04-01

    As a part of the work carried out a project supported by the Danish council for technology and innovation, we have investigated the option of smoothening standard CNC machined surfaces. In the process of constructing optical prototypes, involving custom-designed optics, the development price and time can become a prohibitively large part of a research budget. Machining the optical surfaces of a molding tool may be done directly using diamond turning, but it is expensive and time consuming. Alternatively, a more standardized and cheaper machining method can be used, however, calling for manual polishing afterwards. Particularly, this last process is expensive as well, and will introduce an uncertainty in precisely how much material the polishing process will remove, introducing roughness on a larger lateral scale, such as waviness. Therefore, we have investigated the possibilities of smoothening surfaces of various shapes succeeding a standard CNC machining process. Different coatings have been tested for their abilities to fill and smoothen out structures of larger scales, while removing the small-scale roughness, which is critical for optical uses. In this work we will present an optical element, designed for optical spatial filtering velocimetry. The spatial filter is the key component in an optical sensor for non-contact measurement of surface vibrations, based on speckle dynamics. The optical element is casted in silicon. The results of smoothing an optical element will be demonstrated, and the sensor will be demonstrated for real-time measurements.

  19. Enhanced codebook algorithm for fast moving object detection from dynamic background using scene visual perception

    NASA Astrophysics Data System (ADS)

    Mousse, Mikaël A.; Motamed, Cina; Ezin, Eugène C.

    2016-11-01

    The detection of moving objects in a video sequence is the first step in an automatic video surveillance system. This work proposes an enhancement of a codebook-based algorithm for moving objects extraction. The proposed algorithm used a perceptual-based approach to optimize foreground information extraction complexity by using a modified codebook algorithm. The purpose of the adaptive strategy is to reduce the computational complexity of the foreground detection algorithm while maintaining its global accuracy. In this algorithm, we use a superpixels segmentation approach to model the spatial dependencies between pixels. The processing of the superpixels is controlled to focus it on the superpixels that are near to the possible location of foreground objects. The performance of the proposed algorithm is evaluated and compared to other algorithms of the state of the art using a public dataset that proposes sequences with a dynamic background. Experimental results prove that the proposed algorithm obtained the best the frame processing rate during the foreground detection.

  20. Rapid Determination of Fast Protein Dynamics from NMR Chemical Exchange Saturation Transfer Data.

    PubMed

    Gu, Yina; Hansen, Alexandar L; Peng, Yu; Brüschweiler, Rafael

    2016-02-24

    Functional motions of (15)N-labeled proteins can be monitored by solution NMR spin relaxation experiments over a broad range of timescales. These experiments however typically take of the order of several days to a week per protein. Recently, NMR chemical exchange saturation transfer (CEST) experiments have emerged to probe slow millisecond motions complementing R1ρ and CPMG-type experiments. CEST also simultaneously reports on site-specific R1 and R2 parameters. It is shown here how CEST-derived R1 and R2 relaxation parameters can be measured within a few hours at an accuracy comparable to traditional relaxation experiments. Using a "lean" version of the model-free approach S(2) order parameters can be determined that match those from the standard model-free approach applied to (15)N R1, R2 , and {(1)H}-(15)N NOE data. The new methodology, which is demonstrated for ubiquitin and arginine kinase (42 kDa), should serve as an effective screening tool of protein dynamics from picosecond-to-millisecond timescales.

  1. Dynamic Changes in the Intracellular Association of Selected Rab Small GTPases with MHC Class II and DM during Dendritic Cell Maturation

    PubMed Central

    Pérez-Montesinos, Gibrán; López-Ortega, Orestes; Piedra-Reyes, Jessica; Bonifaz, Laura C.; Moreno, José

    2017-01-01

    Antigen processing for presentation by major histocompatibility complex class II (MHCII) molecules requires the latter to travel through the endocytic pathway together with its chaperons: the invariant chain (Ii) and DM. Nevertheless, the nature of the compartments where MHCII molecules travel to acquire peptides lacks definition regarding molecules involved in intracellular vesicular trafficking, such as Rab small GTPases. We aimed to define which Rab proteins are present during the intracellular transport of MHCII, DM, and Ii through the endocytic pathway on their route to the cell surface during dendritic cell (DC) maturation. We examined, by means of three-color confocal microscopy, the association of MHCII, DM, and Ii with Rab5, Rab7, Rab9, and Rab11 during the maturation of bone marrow-derived or spleen DC in response to LPS as an inflammatory stimulus. Prior to the stage of immature DC, MHCII migrated from diffuse small cytoplasmic vesicles, predominantly Rab5+Rab7− and Rab5+Rab7+ into a pericentriolar Rab5+Rab7+Rab9+ cluster, with Rab11+ areas. As DC reached the mature phenotype, MHCII left the pericentriolar endocytic compartments toward the cell surface in Rab11+ and Rab9+Rab11+ vesicles. The invariant chain and MHCII transport pathways were not identical. DM and MHCII appeared to arrive to pericentriolar endocytic compartments of immature DC through partially different routes. The association of MHCII molecules with distinct Rab GTPases during DC maturation suggests that after leaving the biosynthetic pathway, MHCII sequentially traffic from typical early endosomes to multivesicular late endosomes to finally arrive at the cell surface in Rab11+ recycling-type endosomes. In immature DCs, DM encounters transiently MHCII in the Rab5+Rab7+Rab9+ compartments, to remain there in mature DC.

  2. Light generation of intracellular Ca2+ signals by a genetically encoded protein BACCS

    PubMed Central

    Ishii, Tomohiro; Sato, Koji; Kakumoto, Toshiyuki; Miura, Shigenori; Touhara, Kazushige; Takeuchi, Shoji; Nakata, Takao

    2015-01-01

    Ca2+ signals are highly regulated in a spatiotemporal manner in numerous cellular physiological events. Here we report a genetically engineered blue light-activated Ca2+ channel switch (BACCS), as an optogenetic tool for generating Ca2+ signals. BACCS opens Ca2+-selective ORAI ion channels in response to light. A BACCS variant, dmBACCS2, combined with Drosophila Orai, elevates the Ca2+ concentration more rapidly, such that Ca2+ elevation in mammalian cells is observed within 1 s on light exposure. Using BACCSs, we successfully control cellular events including NFAT-mediated gene expression. In the mouse olfactory system, BACCS mediates light-dependent electrophysiological responses. Furthermore, we generate BACCS mutants, which exhibit fast and slow recovery of intracellular Ca2+. Thus, BACCSs are a useful optogenetic tool for generating temporally various intracellular Ca2+ signals with a large dynamic range, and will be applicable to both in vitro and in vivo studies. PMID:26282514

  3. Structural rearrangement of the intracellular domains during AMPA receptor activation

    PubMed Central

    Zachariassen, Linda G.; Katchan, Ljudmila; Jensen, Anna G.; Pickering, Darryl S.; Plested, Andrew J. R.

    2016-01-01

    α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are ligand-gated ion channels that mediate the majority of fast excitatory neurotransmission in the central nervous system. Despite recent advances in structural studies of AMPARs, information about the specific conformational changes that underlie receptor function is lacking. Here, we used single and dual insertion of GFP variants at various positions in AMPAR subunits to enable measurements of conformational changes using fluorescence resonance energy transfer (FRET) in live cells. We produced dual CFP/YFP-tagged GluA2 subunit constructs that had normal activity and displayed intrareceptor FRET. We used fluorescence lifetime imaging microscopy (FLIM) in live HEK293 cells to determine distinct steady-state FRET efficiencies in the presence of different ligands, suggesting a dynamic picture of the resting state. Patch-clamp fluorometry of the double- and single-insert constructs showed that both the intracellular C-terminal domain (CTD) and the loop region between the M1 and M2 helices move during activation and the CTD is detached from the membrane. Our time-resolved measurements revealed unexpectedly complex fluorescence changes within these intracellular domains, providing clues as to how posttranslational modifications and receptor function interact. PMID:27313205

  4. Melt detection of Fe-Ni at high-pressures using atomic dynamics measurements and a fast temperature readout spectrometer

    NASA Astrophysics Data System (ADS)

    Zhang, D.; Jackson, J. M.; Zhao, J.; Sturhahn, W.; Alp, E. E.; Hu, M.; Toellner, T. S.

    2013-12-01

    significant for materials near their melting points. To accurately capture this effect and reduce uncertainties in melting temperatures, we have developed a Fast Temperature Readout (FasTeR) spectrometer in-line with nuclear resonance scattering measurements under extreme conditions at Sector 3-ID-B of the Advanced Photon Source. Dedicated to determining the sample's temperature near its melting point, FasTeR features a fast readout rate (~100 Hz), high sensitivity, large dynamic range and well-constrained focus. FasTeR may also be ideal for a variety of short time-scale measurements conducted at high-temperatures. FasTeR has been successfully combined with SMS measurements on compressed fcc-structured Fe alloyed with 10 wt% Ni to determine the melting curve by monitoring the dynamics of the atoms. References: Fei, Y., Bertka, C.M. (2005): The interior of Mars. Science 308, 1120-1121 Jackson et al. (2013): Melting of compressed iron by monitoring atomic dynamics, EPSL, 362, 143-150 Margot et al. (2007): Large longitude libration of Mercury reveals a molten core. Science 316, 710-714 McDonough, W.F., Sun, S.S. (1995): The composition of the Earth. Chem. Geol. 120, 223-253

  5. Caudal fin in the white shark, Carcharodon carcharias (Lamnidae): a dynamic propeller for fast, efficient swimming.

    PubMed

    Lingham-Soliar, Theagarten

    2005-05-01

    The caudal peduncle and caudal fin of Carcharodon carcharias together form a dynamic locomotory structure. The caudal peduncle is a highly modified, dorsoventrally compressed and rigid structure that facilitates the oscillations of the caudal fin. Its stiffness appears to be principally achieved by a thick layer of adipose tissue ranging from 28-37% of its cross-sectional area, reinforced by cross-woven collagen fibers. Numerous overlying layers of collagen fibers of the stratum compactum, oriented in steep left- and right-handed helices (approximately 65 degrees to the shark's long axis), prevent bowstringing of the perimysial fibers, which lie just below the dermal layer. Perimysial fibers, muscles, and the notochord are restricted to the dorsal lobe of the caudal fin and comprise the bulk of its mass. Adipose tissue reinforces the leading edge of the dorsal lobe of the caudal fin and contributes to maintaining the ideal cross-sectional geometry required of an advanced hydrofoil. Most of the mass of the ventral lobe consists of the ceratotrichia or fin rays separated by thin partitions of connective tissue. Dermal fibers of the stratum compactum of the dorsal lobe occur in numerous distinct layers. The layers are more complex than in other sharks and appear to reflect a hierarchical development in C. carcharias. The fiber layer comprises a number of thick fiber bundles along the height of the layer and the layers get thicker deeper into the stratum compactum. Each of these layers alternates with a layer a single fiber-bundle deep, a formation thought to give stability to the stratum compactum and to enable freer movements of the fiber system. In tangential sections of the stratum compactum the fiber bundles in the dorsal lobe can be seen oriented with respect to the long axis of the shark at approximately 55-60 degrees in left- and right-handed helices. Because of the backward sweep of the dorsal lobe (approximately 55 degrees to the shark's long axis) the right

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

    SciTech Connect

    Chen, J.; Zhuang, G. Li, Q.; Liu, Y.; Gao, L.; Zhou, Y. N.; Jian, X.; Xiong, C. Y.; Wang, Z. J.; Brower, D. L.; Ding, W. X.

    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.

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

    PubMed

    Chen, J; Zhuang, G; Li, Q; Liu, Y; Gao, L; Zhou, Y N; Jian, X; Xiong, C Y; Wang, Z J; Brower, D L; Ding, W X

    2014-11-01

    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.

  8. Examining Cortical Dynamics and Connectivity with Simultaneous Single-Pulse Transcranial Magnetic Stimulation and Fast Optical Imaging

    PubMed Central

    Parks, Nathan A.; Maclin, Edward L.; Low, Kathy A.; Beck, Diane M.; Fabiani, Monica; Gratton, Gabriele

    2011-01-01

    Transcranial magnetic stimulation (TMS) is a widely used experimental and clinical technique that directly induces activity in human cortex using magnetic fields. However, the neural mechanisms of TMS-induced activity are not well understood. Here, we introduce a novel method of imaging TMS-evoked activity using a non-invasive fast optical imaging tool, the event-related optical signal (EROS). EROS measures changes in the scattering of near-infrared light that occur synchronously with electrical activity in cortical tissue. EROS has good temporal and spatial resolution, allowing the dynamics and spatial spread of a TMS pulse to be measured. We used EROS to monitor activity induced in primary motor cortex (M1) by a TMS pulse. Left- and right-hand representations were mapped using standard TMS procedures. Optical sources and detectors mounted on thin rubber patches were then centered on M1 hand representations. EROS was recorded bilaterally from motor cortex while unilateral TMS was simultaneously delivered. Robust ipsilateral EROS activations were apparent within 16 ms of a pulse for TMS delivered to both left and right hemispheres. Clear motor evoked potentials (MEPs) were also elicited by these TMS pulses. Movement artifacts could be excluded as a source of EROS, as no activation was present on short-distance optical channels. For left hemisphere TMS subsequent (40 ms) contralateral activity was also present, presumably due to trans-synaptic propagation of TMS-evoked activity. Results demonstrate that concurrent TMS/EROS is a viable and potentially powerful method for studying TMS-induced activity in the human brain. With further development, this technique may be applied more broadly in the study of the dynamics of causal cortico-cortical connectivity. PMID:21925608

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

    PubMed Central

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

    2013-01-01

    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-anilinonapthalene-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. PMID:23760106

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

    PubMed

    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.

  11. Label-free fast 3D coherent imaging reveals pancreatic islet micro-vascularization and dynamic blood flow

    PubMed Central

    Berclaz, Corinne; Szlag, Daniel; Nguyen, David; Extermann, Jérôme; Bouwens, Arno; Marchand, Paul J.; Nilsson, Julia; Schmidt-Christensen, Anja; Holmberg, Dan; Grapin-Botton, Anne; Lasser, Theo

    2016-01-01

    In diabetes, pancreatic β-cells play a key role. These cells are clustered within structures called islets of Langerhans inside the pancreas and produce insulin, which is directly secreted into the blood stream. The dense vascularization of islets of Langerhans is critical for maintaining a proper regulation of blood glucose homeostasis and is known to be affected from the early stage of diabetes. The deep localization of these islets inside the pancreas in the abdominal cavity renders their in vivo visualization a challenging task. A fast label-free imaging method with high spatial resolution is required to study the vascular network of islets of Langerhans. Based on these requirements, we developed a label-free and three-dimensional imaging method for observing islets of Langerhans using extended-focus Fourier domain Optical Coherence Microscopy (xfOCM). In addition to structural imaging, this system provides three-dimensional vascular network imaging and dynamic blood flow information within islets of Langerhans. We propose our method to deepen the understanding of the interconnection between diabetes and the evolution of the islet vascular network. PMID:27895996

  12. From electron microscopy to molecular cell biology, molecular genetics and structural biology: intracellular transport and kinesin superfamily proteins, KIFs: genes, structure, dynamics and functions.

    PubMed

    Hirokawa, Nobutaka

    2011-01-01

    Cells transport and sort various proteins and lipids following synthesis as distinct types of membranous organelles and protein complexes to the correct destination at appropriate velocities. This intracellular transport is fundamental for cell morphogenesis, survival and functioning not only in highly polarized neurons but also in all types of cells in general. By developing quick-freeze electron microscopy (EM), new filamentous structures associated with cytoskeletons are uncovered. The characterization of chemical structures and functions of these new filamentous structures led us to discover kinesin superfamily molecular motors, KIFs. In this review, I discuss the identification of these new structures and characterization of their functions using molecular cell biology and molecular genetics. KIFs not only play significant roles by transporting various cargoes along microtubule rails, but also play unexpected fundamental roles on various important physiological processes such as learning and memory, brain wiring, development of central nervous system and peripheral nervous system, activity-dependent neuronal survival, development of early embryo, left-right determination of our body and tumourigenesis. Furthermore, by combining single-molecule biophysics with structural biology such as cryo-electrom microscopy and X-ray crystallography, atomic structures of KIF1A motor protein of almost all states during ATP hydrolysis have been determined and a common mechanism of motility has been proposed. Thus, this type of studies could be a good example of really integrative multidisciplinary life science in the twenty-first century.

  13. Dynamics of intracellular phospholipid membrane organization during oocyte maturation and successful vitrification of immature oocytes retrieved by ovum pick-up in cattle.

    PubMed

    Aono, Akira; Nagatomo, Hiroaki; Takuma, Tetsuya; Nonaka, Rika; Ono, Yoshitaka; Wada, Yasuhiko; Abe, Yasuyuki; Takahashi, Masashi; Watanabe, Tomomasa; Kawahara, Manabu

    2013-05-01

    The objective was to determine if immature bovine oocytes with cumulus cells at the germinal vesicle (GV) stage could be vitrified by aluminum sheets (AS; pieces of sheet-like aluminum foil). Cleavage rates in fertilized oocytes previously vitrified by the AS procedure were higher than those vitrified by a nylon-mesh holder (NM) procedure (89.3 ± 2.1% vs. 65.0 ± 3.7%). Cleaved embryos derived from the AS but not from the NM procedures developed to blastocysts. Furthermore, to investigate the effects of vitrifying GV oocytes on cytoplasmic structure and on the ability to undergo cytoplasmic changes, the intracellular phospholipid membrane (IM) was stained with the lipophilic fluorescent dye, 3,3'-dioctadecyloxa-carbocyanine perchlorate. After vitrification by AS, the IM remained intact relative to that of oocytes vitrified by NM. During in vitro maturation, reorganization of the IM was also undamaged in oocytes vitrified by AS before oocyte maturation, and the IM within oocytes vitrified by the NM procedure was evidently impaired. Finally, vitrification (AS) was used for GV oocytes collected using the ovum pick-up method. A bull calf was born after in vitro production and subsequent embryo transfer. The vitrification techniques described herein should facilitate generation of viable in vitro production bovine blastocysts using oocytes recovered using the ovum pick-up method.

  14. Dynamic quantification of intracellular calcium and protein tyrosine phosphorylation in cryopreserved boar spermatozoa during short-time incubation with oviductal fluid.

    PubMed

    Kumaresan, A; González, R; Johannisson, A; Berqvist, A-S

    2014-11-01

    Freshly ejaculated boar spermatozoa require several hours of exposure to capacitating conditions to undergo capacitation. We hypothesized that cryopreserved boar spermatozoa might elicit a capacitation response after a relatively shorter time of exposure to capacitating conditions. Washed, frozen-thawed boar spermatozoa were incubated separately with pre-ovulatory isthmic oviductal fluid (EODF), post-ovulatory ODF (MODF), capacitation medium (CM), and noncapacitating medium (NCM) for 60 minutes. Aliquots of spermatozoa were taken at 0, 5, 15, 30, and 60 minutes during incubation and sperm kinematics, intracellular calcium [Ca2(+)]i content, and protein tyrosine phosphorylation (PTP) were studied. The proportion of motile spermatozoa increased significantly after 5 minutes of incubation with EODF. A similar increase was not observed in the other groups. During the initial 5 minutes of incubation, the proportion of spermatozoa with high [Ca(2+)]i decreased significantly in all four groups. The proportion of tyrosine phosphorylated spermatozoa increased from 6.49 ± 1.93% to 15.42 ± 3.58% and 18.41 ± 1.57% in EODF and MODF groups, respectively, at 5 minutes of incubation. Neither CM nor NCM elicited any immediate effect on PTP in spermatozoa. There was a positive and significant correlation between [Ca(2+)]i and sperm motility (P = 0.009). It may be concluded that frozen-thawed boar spermatozoa undergo capacitation-associated changes after a relatively short exposure to EODF, and there are some subpopulations of spermatozoa that undergo PTP despite possessing low [Ca(2+)]i.

  15. Controlling slow and fast light and dynamic pulse-splitting with tunable optical gain in a whispering-gallery-mode microcavity

    NASA Astrophysics Data System (ADS)

    Asano, M.; Özdemir, Ş. K.; Chen, W.; Ikuta, R.; Yang, L.; Imoto, N.; Yamamoto, T.

    2016-05-01

    We report controllable manipulation of slow and fast light in a whispering-gallery-mode microtoroid resonator fabricated from Erbium (Er3+) doped silica. We observe continuous transition of the coupling between the fiber-taper waveguide and the microresonator from undercoupling to critical coupling and then to overcoupling regimes by increasing the pump power even though the spatial distance between the resonator and the waveguide was kept fixed. This, in turn, enables switching from fast to slow light and vice versa just by increasing the optical gain. An enhancement of delay of two-fold over the passive silica resonator (no optical gain) was observed in the slow light regime. Moreover, we show dynamic pulse splitting and its control in slow/fast light systems using optical gain.

  16. Dynamic magnetic resonance imaging of endoscopic third ventriculostomy patency with differently acquired fast imaging with steady-state precession sequences.

    PubMed

    Lucic, Milos A; Koprivsek, Katarina; Kozic, Dusko; Spero, Martina; Spirovski, Milena; Lucic, Silvija

    2014-08-16

    The aim of the study was to determine the possibilities of two differently acquired two-dimensional fast imaging with steady-state precession (FISP 2D) magnetic resonance sequences in estimation of the third ventricle floor fenestration patency after endoscopic third ventriculostomy (ETV) in the subjects with aqueductal stenosis/obstruction.Fifty eight subjects (37 males, 21 females, mean age 27 years) with previously successfully performed ETV underwent brain MRI on 1.5T MR imager 3-6 months after the procedure. Two different FISP 2D sequences (one included in the standard vendor provided software package, and the other, experimentally developed by our team) were performed respectively at two fixed slice positions: midsagittal and perpendicular to the ETV fenestration, and displayed in a closed-loop cinematographic format in order to estimate the patency. The ventricular volume reduction has been observed as well.Cerebrospinal fluid (CSF) flow through the ETV fenestration was observed in midsagittal plane with both FISP 2D sequences in 93.11% subjects, while in 6.89% subjects the dynamic CSF flow MRI was inconclusive. In the perpendicular plane CSF flow through the ETV fenestration was visible only by use of experimentally developed FISP 2D (TR30/FA70) sequence. Postoperative volume reduction of lateral and third ventricle was detected in 67.24% subjects.Though both FISP 2D sequences acquired in midsagittal plane may be used to estimate the effects of performed ETV, due to achieved higher CSF pulsatile flow sensitivity, only the use of FISP 2D (TR30/FA70) sequence enables the estimation of the treatment effect in perpendicular plane in the absence of phase-contrast sequences. 

  17. Effect of Ca2+ efflux pathway distribution and exogenous Ca2+ buffers on intracellular Ca2+ dynamics in the rat ventricular myocyte: a simulation study.

    PubMed

    Pásek, Michal; Simurda, Jiří; Orchard, Clive H

    2014-01-01

    We have used a previously published computer model of the rat cardiac ventricular myocyte to investigate the effect of changing the distribution of Ca(2+) efflux pathways (SERCA, Na(+)/Ca(2+) exchange, and sarcolemmal Ca(2+) ATPase) between the dyad and bulk cytoplasm and the effect of adding exogenous Ca(2+) buffers (BAPTA or EGTA), which are used experimentally to differentially buffer Ca(2+) in the dyad and bulk cytoplasm, on cellular Ca(2+) cycling. Increasing the dyadic fraction of a particular Ca(2+) efflux pathway increases the amount of Ca(2+) removed by that pathway, with corresponding changes in Ca(2+) efflux from the bulk cytoplasm. The magnitude of these effects varies with the proportion of the total Ca(2+) removed from the cytoplasm by that pathway. Differences in the response to EGTA and BAPTA, including changes in Ca(2+)-dependent inactivation of the L-type Ca(2+) current, resulted from the buffers acting as slow and fast "shuttles," respectively, removing Ca(2+) from the dyadic space. The data suggest that complex changes in dyadic Ca(2+) and cellular Ca(2+) cycling occur as a result of changes in the location of Ca(2+) removal pathways or the presence of exogenous Ca(2+) buffers, although changing the distribution of Ca(2+) efflux pathways has relatively small effects on the systolic Ca(2+) transient.

  18. Bright Two-Photon Emission and Ultra-Fast Relaxation Dynamics in a DNA-Templated Nanocluster Investigated by Ultra-Fast Spectroscopy

    DTIC Science & Technology

    2012-01-01

    dynamics. A new subclass of fluorescent silver nanoclusters (Ag NCs) are NanoCluster Beacons. NanoCluster Beacons consist of a weakly emissive Ag NC...NanoCluster Beacons consist of a weakly emissive Ag NC templated on a single stranded DNA ("Ag NC on ssDNA’’) that becomes highly fluorescent when...appear at a size near ~2.2nm. This is consistent with simulations from a free-electron model proposed for MPCs. The use of ultrafast techniques on

  19. Nanovehicular Intracellular Delivery Systems

    PubMed Central

    PROKOP, ALES; DAVIDSON, JEFFREY M.

    2013-01-01

    This article provides an overview of principles and barriers relevant to intracellular drug and gene transport, accumulation and retention (collectively called as drug delivery) by means of nanovehicles (NV). The aim is to deliver a cargo to a particular intracellular site, if possible, to exert a local action. Some of the principles discussed in this article apply to noncolloidal drugs that are not permeable to the plasma membrane or to the blood–brain barrier. NV are defined as a wide range of nanosized particles leading to colloidal objects which are capable of entering cells and tissues and delivering a cargo intracelullarly. Different localization and targeting means are discussed. Limited discussion on pharmacokinetics and pharmacodynamics is also presented. NVs are contrasted to micro-delivery and current nanotechnologies which are already in commercial use. Newer developments in NV technologies are outlined and future applications are stressed. We also briefly review the existing modeling tools and approaches to quantitatively describe the behavior of targeted NV within the vascular and tumor compartments, an area of particular importance. While we list “elementary” phenomena related to different level of complexity of delivery to cancer, we also stress importance of multi-scale modeling and bottom-up systems biology approach. PMID:18200527

  20. Evolution of intracellular compartmentalization.

    PubMed

    Diekmann, Yoan; Pereira-Leal, José B

    2013-01-15

    Cells compartmentalize their biochemical functions in a variety of ways, notably by creating physical barriers that separate a compartment via membranes or proteins. Eukaryotes have a wide diversity of membrane-based compartments, many that are lineage- or tissue-specific. In recent years, it has become increasingly evident that membrane-based compartmentalization of the cytosolic space is observed in multiple prokaryotic lineages, giving rise to several types of distinct prokaryotic organelles. Endosymbionts, previously believed to be a hallmark of eukaryotes, have been described in several bacteria. Protein-based compartments, frequent in bacteria, are also found in eukaryotes. In the present review, we focus on selected intracellular compartments from each of these three categories, membrane-based, endosymbiotic and protein-based, in both prokaryotes and eukaryotes. We review their diversity and the current theories and controversies regarding the evolutionary origins. Furthermore, we discuss the evolutionary processes acting on the genetic basis of intracellular compartments and how those differ across the domains of life. We conclude that the distinction between eukaryotes and prokaryotes no longer lies in the existence of a compartmentalized cell plan, but rather in its complexity.

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

    SciTech Connect

    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

  2. Dynamics of Actin Stress Fibers and Focal Adhesions during Slow Migration in Swiss 3T3 Fibroblasts: Intracellular Mechanism of Cell Turning

    PubMed Central

    Miyoshi, Hiromi; Miura, Takuya; Tanaka, Hiroto; Tsubota, Ken-ichi; Liu, Hao

    2016-01-01

    To understand the mechanism regulating the spontaneous change in polarity that leads to cell turning, we quantitatively analyzed the dynamics of focal adhesions (FAs) coupling with the self-assembling actin cytoskeletal structure in Swiss 3T3 fibroblasts. Fluorescent images were acquired from cells expressing GFP-actin and RFP-zyxin by laser confocal microscopy. On the basis of the maximum area, duration, and relocation distance of FAs extracted from the RFP-zyxin images, the cells could be divided into 3 regions: the front region, intermediate lateral region, and rear region. In the intermediate lateral region, FAs appeared close to the leading edge and were stabilized gradually as its area increased. Simultaneously, bundled actin stress fibers (SFs) were observed vertically from the positions of these FAs, and they connected to the other SFs parallel to the leading edge. Finally, these connecting SFs fused to form a single SF with matured FAs at both ends. This change in SF organization with cell retraction in the first cycle of migration followed by a newly formed protrusion in the next cycle is assumed to lead to cell turning in migrating Swiss 3T3 fibroblasts. PMID:28119928

  3. How Fast Is Fast?

    ERIC Educational Resources Information Center

    Korn, Abe

    1994-01-01

    Presents an activity that enables students to answer for themselves the question of how fast a body must travel before the nonrelativistic expression must be replaced with the correct relativistic expression by deciding on the accuracy required in describing the kinetic energy of a body. (ZWH)

  4. Fast MS/MS acquisition without dynamic exclusion enables precise and accurate quantification of proteome by MS/MS fragment intensity

    PubMed Central

    Zhang, Shen; Wu, Qi; Shan, Yichu; Zhao, Qun; Zhao, Baofeng; Weng, Yejing; Sui, Zhigang; Zhang, Lihua; Zhang, Yukui

    2016-01-01

    Most currently proteomic studies use data-dependent acquisition with dynamic exclusion to identify and quantify the peptides generated by the digestion of biological sample. Although dynamic exclusion permits more identifications and higher possibility to find low abundant proteins, stochastic and irreproducible precursor ion selection caused by dynamic exclusion limit the quantification capabilities, especially for MS/MS based quantification. This is because a peptide is usually triggered for fragmentation only once due to dynamic exclusion. Therefore the fragment ions used for quantification only reflect the peptide abundances at that given time point. Here, we propose a strategy of fast MS/MS acquisition without dynamic exclusion to enable precise and accurate quantification of proteome by MS/MS fragment intensity. The results showed comparable proteome identification efficiency compared to the traditional data-dependent acquisition with dynamic exclusion, better quantitative accuracy and reproducibility regardless of label-free based quantification or isobaric labeling based quantification. It provides us with new insights to fully explore the potential of modern mass spectrometers. This strategy was applied to the relative quantification of two human disease cell lines, showing great promises for quantitative proteomic applications. PMID:27198003

  5. Integrative Physiology of Fasting.

    PubMed

    Secor, Stephen M; Carey, Hannah V

    2016-03-15

    Extended bouts of fasting are ingrained in the ecology of many organisms, characterizing aspects of reproduction, development, hibernation, estivation, migration, and infrequent feeding habits. The challenge of long fasting episodes is the need to maintain physiological homeostasis while relying solely on endogenous resources. To meet that challenge, animals utilize an integrated repertoire of behavioral, physiological, and biochemical responses that reduce metabolic rates, maintain tissue structure and function, and thus enhance survival. We have synthesized in this review the integrative physiological, morphological, and biochemical responses, and their stages, that characterize natural fasting bouts. Underlying the capacity to survive extended fasts are behaviors and mechanisms that reduce metabolic expenditure and shift the dependency to lipid utilization. Hormonal regulation and immune capacity are altered by fasting; hormones that trigger digestion, elevate metabolism, and support immune performance become depressed, whereas hormones that enhance the utilization of endogenous substrates are elevated. The negative energy budget that accompanies fasting leads to the loss of body mass as fat stores are depleted and tissues undergo atrophy (i.e., loss of mass). Absolute rates of body mass loss scale allometrically among vertebrates. Tissues and organs vary in the degree of atrophy and downregulation of function, depending on the degree to which they are used during the fast. Fasting affects the population dynamics and activities of the gut microbiota, an interplay that impacts the host's fasting biology. Fasting-induced gene expression programs underlie the broad spectrum of integrated physiological mechanisms responsible for an animal's ability to survive long episodes of natural fasting.

  6. 3D quantification of dynamic fluid-fluid interfaces in porous media with fast x-ray microtomography: A comparison with quasi-equilibrium methods

    NASA Astrophysics Data System (ADS)

    Meisenheimer, D.; Brueck, C. L.; Wildenschild, D.

    2015-12-01

    X-ray microtomography imaging of fluid-fluid interfaces in three-dimensional porous media allows for the testing of thermodynamically derived predictions that seek a unique relationship between capillary pressure, fluid saturation, and specific interfacial area (Pc-Sw-Anw). Previous experimental studies sought to test this functional dependence under quasi-equilibrium conditions (assumed static on the imaging time-scale); however, applying predictive models developed under static conditions for dynamic scenarios can lead to substantial flaws in predicted outcomes. Theory and models developed using dynamic data can be verified using fast x-ray microtomography which allows for the unprecedented measurement of developing interfacial areas, curvatures, and trapping behaviors of fluid phases in three-dimensional systems. We will present results of drainage and imbibition experiments of air and water within a mixture of glass beads. The experiments were performed under both quasi-equilibrium and dynamic conditions at the Advanced Photon Source (APS) at Argonne National Laboratory. Fast x-ray microtomography was achieved by utilizing the high brilliance of the x-ray beam at the APS under pink-beam conditions where the white beam is modified with a 4 mm Al absorber and a 0.8 mrad Pt-coated mirror to eliminate low and high-energy photons, respectively. We present a comparison of the results from the quasi-equilibrium and dynamic experiments in an effort to determine if the Pc-Sw-Anw relationship is comparable under either experimental condition and to add to the discussion on whether the Pc-Sw-Anw relationship is unique as hypothesized by existing theory.

  7. Direct and indirect methods for studying the energetics and dynamics of the Auger Doppler effect in femtosecond ultra-fast dissociation

    NASA Astrophysics Data System (ADS)

    Björneholm, O.

    2001-09-01

    Molecules may fragment within a few femtoseconds after core-excitation, a phenomenon known as ultra-fast dissociation. With the aim of providing an understanding of the fundamental phenomenology of the Auger Doppler effect, two methods are presented to study the energetics and dynamics, i.e., the kinetic energy release and the fragment velocities in such processes. The first, direct, method is based on the shifts in kinetic energy of the Auger electrons due to the velocity acquired by the fragment in the ultra-fast dissociation process, i.e., the Auger Doppler effect. The second, indirect, method is based on total-energy arguments in a Born-Haber cycle for excitation, dissociation, and ionization. A combination of the two methods is shown to be able to reproduce experimental spectra well. Based on this, predictions are made for other, yet unstudied, molecular systems. It is also shown that the Auger Doppler effect is not static, but will exhibit dynamic photon energy dependence. The complete energetics of the three-body dissociation of a molecule into an electron, an ion, and a neutral fragment on a time-scale of a few femtoseconds can thus be accounted for.

  8. Sub-10-nm intracellular bioelectronic probes from nanowire–nanotube heterostructures

    PubMed Central

    Fu, Tian-Ming; Duan, Xiaojie; Jiang, Zhe; Dai, Xiaochuan; Xie, Ping; Cheng, Zengguang; Lieber, Charles M.

    2014-01-01

    The miniaturization of bioelectronic intracellular probes with a wide dynamic frequency range can open up opportunities to study biological structures inaccessible by existing methods in a minimally invasive manner. Here, we report the design, fabrication, and demonstration of intracellular bioelectronic devices with probe sizes less than 10 nm. The devices are based on a nanowire–nanotube heterostructure in which a nanowire field-effect transistor detector is synthetically integrated with a nanotube cellular probe. Sub-10-nm nanotube probes were realized by a two-step selective etching approach that reduces the diameter of the nanotube free-end while maintaining a larger diameter at the nanowire detector necessary for mechanical strength and electrical sensitivity. Quasi-static water-gate measurements demonstrated selective device response to solution inside the nanotube, and pulsed measurements together with numerical simulations confirmed the capability to record fast electrophysiological signals. Systematic studies of the probe bandwidth in different ionic concentration solutions revealed the underlying mechanism governing the time response. In addition, the bandwidth effect of phospholipid coatings, which are important for intracellular recording, was investigated and modeled. The robustness of these sub-10-nm bioelectronics probes for intracellular interrogation was verified by optical imaging and recording the transmembrane resting potential of HL-1 cells. These ultrasmall bioelectronic probes enable direct detection of cellular electrical activity with highest spatial resolution achieved to date, and with further integration into larger chip arrays could provide a unique platform for ultra-high-resolution mapping of activity in neural networks and other systems. PMID:24474745

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

    NASA Astrophysics Data System (ADS)

    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’.

  10. Fast and slow dynamics and the local structure of liquid and supercooled water next to a hydrophobic amino acid.

    PubMed

    Martiniano, H F M C; Galamba, N

    2016-10-05

    We study, through molecular dynamics simulations, the structure and orientational dynamics of water next to a blocked hydrophobic amino acid, valine (Val), above and below the freezing point of water. The structure and the orientational dynamics of waters with four water neighbors (4WN) and less than four water neighbors (L4WN) in the Val's coordination sphere are deconvoluted. We find that in spite of the excluded volume effects waters with L4WN have faster librational dynamics than bulk water, reminiscent of water at the liquid-vapor interface, and faster orientational dynamics than waters with 4WN, at every temperature. Furthermore, our results show that the pronounced decrease of the orientational retardation factor below ∼255 K observed experimentally is mostly caused by the acceleration of the orientational dynamics of waters with L4WN, while waters with 4WN exhibit only moderate acceleration. The differences between the hydrogen-bond acceptor switching mechanism in the shell and the bulk are also analyzed, and no evidence of especially slow OH groups neither in the 4WN nor in the L4WN populations is found. Finally, we show that waters with 4WN have higher tetrahedrality than bulk water at every temperature although this difference decreases at both high and low temperatures.

  11. Damage detection in a cantilever beam under dynamic conditions using a distributed, fast, and high spatial resolution Brillouin interrogator

    NASA Astrophysics Data System (ADS)

    Motil, A.; Davidi, R.; Bergman, A.; Botsev, Y.; Hahami, M.; Tur, M.

    2016-05-01

    The ability of Brillouin-based fiber-optic sensing to detect damage in a moving cantilever beam is demonstrated. A fully computerized, distributed and high spatial resolution (10cm) Fast-BOTDA interrogator (50 full-beam Brillouin-gain-spectra per second) successfully directly detected an abnormally stiffened (i.e., `damaged') 20cm long segment in a 6m Aluminum beam, while the beam was in motion. Damage detection was based on monitoring deviations of the measured strain distribution along the beam from that expected in the undamaged case.

  12. Staying away from the bar: the local dynamical signature of slow and fast bars in the Milky Way

    NASA Astrophysics Data System (ADS)

    Monari, Giacomo; Famaey, Benoit; Siebert, Arnaud; Duchateau, Aurore; Lorscheider, Thibault; Bienaymé, Olivier

    2017-02-01

    Both the three-dimensional density of red clump giants and the gas kinematics in the inner Galaxy indicate that the pattern speed of the Galactic bar could be much lower than previously estimated. Here, we show that such slow bar models are unable to reproduce the bimodality observed in local stellar velocity space. We do so by computing the response of stars in the solar neighbourhood to the gravitational potential of slow and fast bars, in terms of their perturbed distribution function in action-angle space up to second order, as well as by identifying resonantly trapped orbits. We also check that the bimodality is unlikely to be produced through perturbations from spiral arms, and conclude that, contrary to gas kinematics, local stellar kinematics still favour a fast bar in the Milky Way, with a pattern speed of the order of almost twice (and no less than 1.8 times) the circular frequency at the Sun's position. This leaves open the question of the nature of the long flat extension of the bar in the Milky Way.

  13. Investigation of three-dimensional dynamic stall on an airfoil using fast-response pressure-sensitive paint

    NASA Astrophysics Data System (ADS)

    Gardner, A. D.; Klein, C.; Sachs, W. E.; Henne, U.; Mai, H.; Richter, K.

    2014-09-01

    Dynamic stall on a pitching OA209 airfoil in a wind tunnel is investigated at Mach 0.3 and 0.5 using high-speed pressure-sensitive paint (PSP) and pressure measurements. At Mach 0.3, the dynamic stall vortex was observed to propagate faster at the airfoil midline than at the wind-tunnel wall, resulting in a "bowed" vortex shape. At Mach 0.5, shock-induced stall was observed, with initial separation under the shock foot and subsequent expansion of the separated region upstream, downstream and along the breadth of the airfoil. No dynamic stall vortex could be observed at Mach 0.5. The investigation of flow control by blowing showed the potential advantages of PSP over pressure transducers for a complex three-dimensional flow.

  14. INTRACELLULAR SIGNALING AND DEVELOPMENTAL NEUROTOXICITY.

    EPA Science Inventory

    A book chapter in ?Molecular Toxicology: Transcriptional Targets? reviewed the role of intracellular signaling in the developmental neurotoxicity of environmental chemicals. This chapter covered a number of aspects including the development of the nervous system, role of intrace...

  15. Functional genomics of intracellular bacteria.

    PubMed

    de Barsy, Marie; Greub, Gilbert

    2013-07-01

    During the genomic era, a large amount of whole-genome sequences accumulated, which identified many hypothetical proteins of unknown function. Rapidly, functional genomics, which is the research domain that assign a function to a given gene product, has thus been developed. Functional genomics of intracellular pathogenic bacteria exhibit specific peculiarities due to the fastidious growth of most of these intracellular micro-organisms, due to the close interaction with the host cell, due to the risk of contamination of experiments with host cell proteins and, for some strict intracellular bacteria such as Chlamydia, due to the absence of simple genetic system to manipulate the bacterial genome. To identify virulence factors of intracellular pathogenic bacteria, functional genomics often rely on bioinformatic analyses compared with model organisms such as Escherichia coli and Bacillus subtilis. The use of heterologous expression is another common approach. Given the intracellular lifestyle and the many effectors that are used by the intracellular bacteria to corrupt host cell functions, functional genomics is also often targeting the identification of new effectors such as those of the T4SS of Brucella and Legionella.

  16. Rapidly characterizing the fast dynamics of RNA genetic circuitry with cell-free transcription-translation (TX-TL) systems.

    PubMed

    Takahashi, Melissa K; Chappell, James; Hayes, Clarmyra A; Sun, Zachary Z; Kim, Jongmin; Singhal, Vipul; Spring, Kevin J; Al-Khabouri, Shaima; Fall, Christopher P; Noireaux, Vincent; Murray, Richard M; Lucks, Julius B

    2015-05-15

    RNA regulators are emerging as powerful tools to engineer synthetic genetic networks or rewire existing ones. A potential strength of RNA networks is that they may be able to propagate signals on time scales that are set by the fast degradation rates of RNAs. However, a current bottleneck to verifying this potential is the slow design-build-test cycle of evaluating these networks in vivo. Here, we adapt an Escherichia coli-based cell-free transcription-translation (TX-TL) system for rapidly prototyping RNA networks. We used this system to measure the response time of an RNA transcription cascade to be approximately five minutes per step of the cascade. We also show that this response time can be adjusted with temperature and regulator threshold tuning. Finally, we use TX-TL to prototype a new RNA network, an RNA single input module, and show that this network temporally stages the expression of two genes in vivo.

  17. Rapidly Characterizing the Fast Dynamics of RNA Genetic Circuitry with Cell-Free Transcription–Translation (TX-TL) Systems

    PubMed Central

    2014-01-01

    RNA regulators are emerging as powerful tools to engineer synthetic genetic networks or rewire existing ones. A potential strength of RNA networks is that they may be able to propagate signals on time scales that are set by the fast degradation rates of RNAs. However, a current bottleneck to verifying this potential is the slow design-build-test cycle of evaluating these networks in vivo. Here, we adapt an Escherichia coli-based cell-free transcription-translation (TX-TL) system for rapidly prototyping RNA networks. We used this system to measure the response time of an RNA transcription cascade to be approximately five minutes per step of the cascade. We also show that this response time can be adjusted with temperature and regulator threshold tuning. Finally, we use TX-TL to prototype a new RNA network, an RNA single input module, and show that this network temporally stages the expression of two genes in vivo. PMID:24621257

  18. Acceleration of canonical molecular dynamics simulations using macroscopic expansion of the fast multipole method combined with the multiple timestep integrator algorithm

    NASA Astrophysics Data System (ADS)

    Kawata, Masaaki; Mikami, Masuhiro

    A canonical molecular dynamics (MD) simulation was accelerated by using an efficient implementation of the multiple timestep integrator algorithm combined with the periodic fast multiple method (MEFMM) for both Coulombic and van der Waals interactions. Although a significant reduction in computational cost has been obtained previously by using the integrated method, in which the MEFMM was used only to calculate Coulombic interactions (Kawata, M., and Mikami, M., 2000, J. Comput. Chem., in press), the extension of this method to include van der Waals interactions yielded further acceleration of the overall MD calculation by a factor of about two. Compared with conventional methods, such as the velocity-Verlet algorithm combined with the Ewald method (timestep of 0.25fs), the speedup by using the extended integrated method amounted to a factor of 500 for a 100 ps simulation. Therefore, the extended method reduces substantially the computational effort of large scale MD simulations.

  19. Fast protein folding kinetics

    PubMed Central

    Gelman, Hannah; Gruebele, Martin

    2014-01-01

    Fast folding proteins have been a major focus of computational and experimental study because they are accessible to both techniques: they are small and fast enough to be reasonably simulated with current computational power, but have dynamics slow enough to be observed with specially developed experimental techniques. This coupled study of fast folding proteins has provided insight into the mechanisms which allow some proteins to find their native conformation well less than 1 ms and has uncovered examples of theoretically predicted phenomena such as downhill folding. The study of fast folders also informs our understanding of even “slow” folding processes: fast folders are small, relatively simple protein domains and the principles that govern their folding also govern the folding of more complex systems. This review summarizes the major theoretical and experimental techniques used to study fast folding proteins and provides an overview of the major findings of fast folding research. Finally, we examine the themes that have emerged from studying fast folders and briefly summarize their application to protein folding in general as well as some work that is left to do. PMID:24641816

  20. Fast-spiking GABA circuit dynamics in the auditory cortex predict recovery of sensory processing following peripheral nerve damage.

    PubMed

    Resnik, Jennifer; Polley, Daniel B

    2017-03-21

    Cortical neurons remap their receptive fields and rescale sensitivity to spared peripheral inputs following sensory nerve damage. To address how these plasticity processes are coordinated over the course of functional recovery, we tracked receptive field reorganization, spontaneous activity, and response gain from individual principal neurons in the adult mouse auditory cortex over a 50-day period surrounding either moderate or massive auditory nerve damage. We related the day-by-day recovery of sound processing to dynamic changes in the strength of intracortical inhibition from parvalbumin-expressing (PV) inhibitory neurons. Whereas the status of brainstem-evoked potentials did not predict the recovery of sensory responses to surviving nerve fibers, homeostatic adjustments in PV-mediated inhibition during the first days following injury could predict the eventual recovery of cortical sound processing weeks later. These findings underscore the potential importance of self-regulated inhibitory dynamics for the restoration of sensory processing in excitatory neurons following peripheral nerve injuries.

  1. Probing ultra-fast processes with high dynamic range at 4th-generation light sources: Arrival time and intensity binning at unprecedented repetition rates

    PubMed Central

    Kovalev, S.; Green, B.; Golz, T.; Maehrlein, S.; Stojanovic, N.; Fisher, A. S.; Kampfrath, T.; Gensch, M.

    2017-01-01

    Understanding dynamics on ultrafast timescales enables unique and new insights into important processes in the materials and life sciences. In this respect, the fundamental pump-probe approach based on ultra-short photon pulses aims at the creation of stroboscopic movies. Performing such experiments at one of the many recently established accelerator-based 4th-generation light sources such as free-electron lasers or superradiant THz sources allows an enormous widening of the accessible parameter space for the excitation and/or probing light pulses. Compared to table-top devices, critical issues of this type of experiment are fluctuations of the timing between the accelerator and external laser systems and intensity instabilities of the accelerator-based photon sources. Existing solutions have so far been only demonstrated at low repetition rates and/or achieved a limited dynamic range in comparison to table-top experiments, while the 4th generation of accelerator-based light sources is based on superconducting radio-frequency technology, which enables operation at MHz or even GHz repetition rates. In this article, we present the successful demonstration of ultra-fast accelerator-laser pump-probe experiments performed at an unprecedentedly high repetition rate in the few-hundred-kHz regime and with a currently achievable optimal time resolution of 13 fs (rms). Our scheme, based on the pulse-resolved detection of multiple beam parameters relevant for the experiment, allows us to achieve an excellent sensitivity in real-world ultra-fast experiments, as demonstrated for the example of THz-field-driven coherent spin precession. PMID:28382317

  2. Cardiac function and perfusion dynamics measured on a beat-by-beat basis in the live mouse using ultra-fast 4D optoacoustic imaging

    NASA Astrophysics Data System (ADS)

    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.

  3. Probing ultra-fast processes with high dynamic range at 4th-generation light sources: Arrival time and intensity binning at unprecedented repetition rates.

    PubMed

    Kovalev, S; Green, B; Golz, T; Maehrlein, S; Stojanovic, N; Fisher, A S; Kampfrath, T; Gensch, M

    2017-03-01

    Understanding dynamics on ultrafast timescales enables unique and new insights into important processes in the materials and life sciences. In this respect, the fundamental pump-probe approach based on ultra-short photon pulses aims at the creation of stroboscopic movies. Performing such experiments at one of the many recently established accelerator-based 4th-generation light sources such as free-electron lasers or superradiant THz sources allows an enormous widening of the accessible parameter space for the excitation and/or probing light pulses. Compared to table-top devices, critical issues of this type of experiment are fluctuations of the timing between the accelerator and external laser systems and intensity instabilities of the accelerator-based photon sources. Existing solutions have so far been only demonstrated at low repetition rates and/or achieved a limited dynamic range in comparison to table-top experiments, while the 4th generation of accelerator-based light sources is based on superconducting radio-frequency technology, which enables operation at MHz or even GHz repetition rates. In this article, we present the successful demonstration of ultra-fast accelerator-laser pump-probe experiments performed at an unprecedentedly high repetition rate in the few-hundred-kHz regime and with a currently achievable optimal time resolution of 13 fs (rms). Our scheme, based on the pulse-resolved detection of multiple beam parameters relevant for the experiment, allows us to achieve an excellent sensitivity in real-world ultra-fast experiments, as demonstrated for the example of THz-field-driven coherent spin precession.

  4. Second-order quadrupolar line shapes under molecular dynamics: An additional transition in the extremely fast regime.

    PubMed

    Hung, Ivan; Wu, Gang; Gan, Zhehong

    2016-12-10

    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 NaNO3 in which the NO3(-) ion undergoes 3-fold jumps confirms the two-stage transition process. The spectra of NaNO3 acquired in the temperature range of 173-413K agree well with simulations using the quantum mechanical formalism. The rate constants for the 3-fold NO3(-) ion jumps span eight orders of magnitude (10(2)-10(10)s(-1)) covering both transitions of the dynamic (17)O line shape.

  5. Dual time-resolved temperature-jump fluorescence and infrared spectroscopy for the study of fast protein dynamics.

    PubMed

    Davis, Caitlin M; Reddish, Michael J; Dyer, R Brian

    2017-02-02

    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 <0.2mOD and a fluorescence sensitivity of 2% of the overall fluorescence intensity. Using a computer controlled QCL to rapidly tune the IR frequency it is possible to create a T-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.

  6. Transmitter release modulation by intracellular Ca2+ buffers in facilitating and depressing nerve terminals of pyramidal cells in layer 2/3 of the rat neocortex indicates a target cell-specific difference in presynaptic calcium dynamics

    PubMed Central

    Rozov, A; Burnashev, N; Sakmann, B; Neher, E

    2001-01-01

    In connections formed by nerve terminals of layer 2/3 pyramidal cells onto bitufted interneurones in young (postnatal day (P)14–15) rat somatosensory cortex, the efficacy and reliability of synaptic transmission were low. At these connections release was facilitated by paired-pulse stimulation (at 10 Hz). In connections formed by terminals of layer 2/3 pyramids with multipolar interneurones efficacy and reliability were high and release was depressed by paired-pulse stimulation. In both types of terminal, however, the voltage-dependent Ca2+ channels that controlled transmitter release were predominantly of the P/Q- and N-subtypes. The relationship between unitary EPSP amplitude and extracellular calcium concentration ([Ca2+]o) was steeper for facilitating than for depressing terminals. Fits to a Hill equation with nH= 4 indicated that the apparent KD of the Ca2+ sensor for vesicle release was two- to threefold lower in depressing terminals than in facilitating ones. Intracellular loading of pyramidal neurones with the fast and slowly acting Ca2+ buffers BAPTA and EGTA differentially reduced transmitter release in these two types of terminal. Unitary EPSPs evoked by pyramidal cell stimulation in bitufted cells were reduced by presynaptic BAPTA and EGTA with half-effective concentrations of ∼0.1 and ∼1 mm, respectively. Unitary EPSPs evoked in multipolar cells were reduced to one-half of control at higher concentrations of presynaptic BAPTA and EGTA (∼0.5 and ∼7 mm, respectively). Frequency-dependent facilitation of EPSPs in bitufted cells was abolished by EGTA at concentrations of > 0.2 mm, suggesting that accumulation of free Ca2+ is essential for facilitation in the terminals contacting bitufted cells. In contrast, facilitation was unaffected or even slightly increased in the terminals loaded with BAPTA in the concentration range 0.02–0.5 mm. This is attributed to partial saturation of exogenously added BAPTA. However, BAPTA at concentrations > 1 mm

  7. Fast dynamics of H{sub 2}O in hydrous aluminosilicate glasses studied with quasielastic neutron scattering

    SciTech Connect

    Indris, Sylvio; Heitjans, Paul; Behrens, Harald; Zorn, Reiner; Frick, Bernhard

    2005-02-01

    We studied the dynamics of dissolved water in aluminosilicate glasses with the compositions NaAlSi{sub 3}O{sub 8}{center_dot}0.3H{sub 2}O, NaAlSi{sub 3}O{sub 8}{center_dot}1.3H{sub 2}O and Ca{sub 0.5}AlSi{sub 3}O{sub 8}{center_dot}1.3H{sub 2}O using quasielastic neutron scattering. As shown by near-infrared spectroscopy on these samples, H{sub 2}O molecules are the predominant hydrous species in the water-rich glasses whereas OH groups bound to tetrahedrally coordinated cations are predominant at low water contents. Backscattering and time-of-flight methods were combined to investigate motional correlation times in the range between 0.2 ps and 2 ns. For the water-rich glasses an elastic scan between 2 K and 420 K shows that the dynamical processes set in at lower temperatures in the Ca-bearing glass than in the Na-bearing glass. This is corroborated by the broadening of the inelastic spectra S(Q,{omega}). The shape of the scattering function S(Q,t) suggests a distribution of activation barriers for the motion of hydrous species in the disordered structure of the glass. The distribution is narrower and the average activation energy is smaller in the Ca-bearing glass than in the Na-bearing glass. No indication for dynamics of hydrous species was found at temperatures up to 520 K in the water-poor glass NaAlSi{sub 3}O{sub 8}{center_dot}0.3H{sub 2}O containing dissolved water mainly in the form of OH groups. It is concluded that H{sub 2}O molecules are the dynamic species in the above-mentioned time regime in the water-rich glasses. The dynamic process is probably a rotation of H{sub 2}O molecules around their bisector axis.

  8. Fast fracture in slow motion: Dynamic fracture and the effect of near-tip elastic nonlinearities in brittle gels

    NASA Astrophysics Data System (ADS)

    Fineberg, Jay

    2012-02-01

    We present recent results of fracture experiments in poly-acrylamide gels [1]. These gels are soft polymers in which the characteristic sound speeds are on the order of a few meters/sec - thereby slowing down fracture dynamics by 3 orders of magnitude. We first show that the dynamics of rapid cracks are universal; the fracture of gels exhibits characteristic features that are identical with those seen in ``classic'' materials such as glass. These include: *Excellent quantitative agreement with the two different equations of motion for single dynamic cracks predicted by Linear Elastic Fracture Mechanics (LEFM) -- each for different classes of loading conditions. *The same branching instabilities, localized waves confined to the crack front, and the characteristic structure formed on the resulting fracture surface as observed in ``standard'' amorphous brittle materials, such as soda-lime glass. We utilize the ``slow motion'' inherent in the fracture of gels to experimentally and theoretically investigate the structure of the deformation fields that surround the tip of highly dynamic cracks. We find that: *The singular fields predicted by LEFM change their structure due to nonlinear elastic effects that dominate the near-tip region [3]. *This non-linear elastic region provides a quantitative explanation for the oscillatory instability of cracks [2,4] as their speed approaches the Rayleigh wave speed. These results provide a quantitative first-principles description of how elastic nonlinearity influences the rapid dynamics of a crack. [4pt] [1] A. Livne, G. Cohen, and J. Fineberg, Physical Rev. Lett. 94, 224301 (2005); T. Goldman, A. Livne, and J. Fineberg, Physical Rev. Lett. 104, 11430 (2010).[0pt] [2] A. Livne, O. Ben-David, and J. Fineberg, Phys. Rev. Lett.,98, 124301 (2007).[0pt] [3] A. Livne, E. Bouchbinder, and J. Fineberg, Phys. Rev. Lett. 101, 264301 (2008);. E. Bouchbinder, A. Livne, and J. Fineberg, Phys. Rev. Lett. 101, 264302 (2008); A. Livne, E

  9. Examination of Rapid Dopamine Dynamics with Fast Scan Cyclic Voltammetry During Intra-oral Tastant Administration in Awake Rats.

    PubMed

    Wickham, Robert J; Park, Jinwoo; Nunes, Eric J; Addy, Nii A

    2015-08-12

    Rapid, phasic dopamine (DA) release in the mammalian brain plays a critical role in reward processing, reinforcement learning, and motivational control. Fast scan cyclic voltammetry (FSCV) is an electrochemical technique with high spatial and temporal (sub-second) resolution that has been utilized to examine phasic DA release in several types of preparations. In vitro experiments in single-cells and brain slices and in vivo experiments in anesthetized rodents have been used to identify mechanisms that mediate dopamine release and uptake under normal conditions and in disease models. Over the last 20 years, in vivo FSCV experiments in awake, freely moving rodents have also provided insight of dopaminergic mechanisms in reward processing and reward learning. One major advantage of the awake, freely moving preparation is the ability to examine rapid DA fluctuations that are time-locked to specific behavioral events or to reward or cue presentation. However, one limitation of combined behavior and voltammetry experiments is the difficulty of dissociating DA effects that are specific to primary rewarding or aversive stimuli from co-occurring DA fluctuations that mediate reward-directed or other motor behaviors. Here, we describe a combined method using in vivo FSCV and intra-oral infusion in an awake rat to directly investigate DA responses to oral tastants. In these experiments, oral tastants are infused directly to the palate of the rat--bypassing reward-directed behavior and voluntary drinking behavior--allowing for direct examination of DA responses to tastant stimuli.

  10. Dopamine Dynamics during Continuous Intracranial Self-Stimulation: Effect of Waveform on Fast-Scan Cyclic Voltammetry Data.

    PubMed

    Rodeberg, Nathan T; Johnson, Justin A; Bucher, Elizabeth S; Wightman, R Mark

    2016-11-16

    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.

  11. Hybrid MPI/OpenMP Implementation of the ORAC Molecular Dynamics Program for Generalized Ensemble and Fast Switching Alchemical Simulations.

    PubMed

    Procacci, Piero

    2016-06-27

    We present a new release (6.0β) of the ORAC program [Marsili et al. J. Comput. Chem. 2010, 31, 1106-1116] with a hybrid OpenMP/MPI (open multiprocessing message passing interface) multilevel parallelism tailored for generalized ensemble (GE) and fast switching double annihilation (FS-DAM) nonequilibrium technology aimed at evaluating the binding free energy in drug-receptor system on high performance computing platforms. The production of the GE or FS-DAM trajectories is handled using a weak scaling parallel approach on the MPI level only, while a strong scaling force decomposition scheme is implemented for intranode computations with shared memory access at the OpenMP level. The efficiency, simplicity, and inherent parallel nature of the ORAC implementation of the FS-DAM algorithm, project the code as a possible effective tool for a second generation high throughput virtual screening in drug discovery and design. The code, along with documentation, testing, and ancillary tools, is distributed under the provisions of the General Public License and can be freely downloaded at www.chim.unifi.it/orac .

  12. Bottom Fixed Platform Dynamics Models Assessing Surface Ice Interactions for Transitional Depth Structures in the Great Lakes: FAST8 – IceDyn

    SciTech Connect

    Karr, Dale G.; Yu, Bingbin; Sirnivas, Senu

    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

  13. Modeling fast electron dynamics with real-time time-dependent density functional theory: application to small molecules and chromophores

    SciTech Connect

    Lopata, Kenneth A.; Govind, Niranjan

    2011-05-10

    The response of matter to external fields forms the basis for a vast wealth of fundamental physical processes ranging from light harvesting to nanoscale electron transport. Accurately modeling ultrafast electron dynamics in excited systems thus o_ers unparalleled insight, but requires an inherently non-linear time-resolved approach. To this end, an e_cient and massively parallel real-time real-space time-dependent density functional theory (RT-TDDFT) implementation in NWChem is presented. The implementation is first validated against linearresponse TDDFT and experimental results for a series of molecules subjected to small electric field perturbations. Second, non-linear excitation of green fluorescent protein is studied, which shows a blue-shift in the spectrum with increasing perturbation, as well as a saturation in absorption. Next, the charge dynamics of optically excited zinc porphyrin is presented in real-time and real-space, with relevance to charge injection in photovoltaic devices. Finally, intermolecular excitation in an adenine-thymine base pair is studied using the BNL range separated functional [Baer, R.; Neuhauser, D. Phys. Rev. Lett. 2005, 94, 043002], demonstrating the utility of a real-time approach in capturing charge transfer processes.

  14. Fast-spiking GABA circuit dynamics in the auditory cortex predict recovery of sensory processing following peripheral nerve damage

    PubMed Central

    Resnik, Jennifer; Polley, Daniel B

    2017-01-01

    Cortical neurons remap their receptive fields and rescale sensitivity to spared peripheral inputs following sensory nerve damage. To address how these plasticity processes are coordinated over the course of functional recovery, we tracked receptive field reorganization, spontaneous activity, and response gain from individual principal neurons in the adult mouse auditory cortex over a 50-day period surrounding either moderate or massive auditory nerve damage. We related the day-by-day recovery of sound processing to dynamic changes in the strength of intracortical inhibition from parvalbumin-expressing (PV) inhibitory neurons. Whereas the status of brainstem-evoked potentials did not predict the recovery of sensory responses to surviving nerve fibers, homeostatic adjustments in PV-mediated inhibition during the first days following injury could predict the eventual recovery of cortical sound processing weeks later. These findings underscore the potential importance of self-regulated inhibitory dynamics for the restoration of sensory processing in excitatory neurons following peripheral nerve injuries. DOI: http://dx.doi.org/10.7554/eLife.21452.001 PMID:28323619

  15. Fast Reactors

    NASA Astrophysics Data System (ADS)

    Esposito, S.; Pisanti, O.

    The following sections are included: * Elementary Considerations * The Integral Equation to the Neutron Distribution * The Critical Size for a Fast Reactor * Supercritical Reactors * Problems and Exercises

  16. A fast Eulerian multiphase flow model for volcanic ash plumes: turbulence, heat transfer and particle non-equilibrium dynamics.

    NASA Astrophysics Data System (ADS)

    Cerminara, Matteo; Esposti Ongaro, Tomaso; Carlo Berselli, Luigi

    2014-05-01

    We have developed a compressible multiphase flow model to simulate the three-dimensional dynamics of turbulent volcanic ash plumes. The model describes the eruptive mixture as a polydisperse fluid, composed of different types of gases and particles, treated as interpenetrating Eulerian phases. Solid phases represent the discrete ash classes into which the total granulometric spectrum is discretized, and can differ by size and density. The model is designed to quickly and accurately resolve important physical phenomena in the dynamics of volcanic ash plumes. In particular, it can simulate turbulent mixing (driving atmospheric entrainment and controlling the heat transfer), thermal expansion (controlling the plume buoyancy), the interaction between solid particles and volcanic gas (including kinetic non-equilibrium effects) and the effects of compressibility (over-pressured eruptions and infrasonic measurements). The model is based on the turbulent dispersed multiphase flow theory for dilute flows (volume concentration <0.001, implying that averaged inter-particle distance is larger than 10 diameters) where particle collisions are neglected. Moreover, in order to speed up the code without losing accuracy, we make the hypothesis of fine particles (Stokes number <0.2 , i.e., volcanic ash particles finer then a millimeter), so that we are able to consider non-equilibrium effects only at the first order. We adopt LES formalism (which is preferable in transient regimes) for compressible flows to model the non-linear coupling between turbulent scales and the effect of sub-grid turbulence on the large-scale dynamics. A three-dimensional numerical code has been developed basing on the OpenFOAM computational framework, a CFD open source parallel software package. Numerical benchmarks demonstrate that the model is able to capture important non-equilibrium phenomena in gas-particle mixtures, such as particle clustering and ejection from large-eddy turbulent structures, as well

  17. Enzyme-modified carbon-fiber microelectrode for the quantification of dynamic fluctuations of nonelectroactive analytes using fast-scan cyclic voltammetry.

    PubMed

    Lugo-Morales, Leyda Z; Loziuk, Philip L; Corder, Amanda K; Toups, J Vincent; Roberts, James G; McCaffrey, Katherine A; Sombers, Leslie A

    2013-09-17

    Neurotransmission occurs on a millisecond time scale, but conventional methods for monitoring nonelectroactive neurochemicals are limited by slow sampling rates. Despite a significant global market, a sensor capable of measuring the dynamics of rapidly fluctuating, nonelectroactive molecules at a single recording site with high sensitivity, electrochemical selectivity, and a subsecond response time is still lacking. To address this need, we have enabled the real-time detection of dynamic glucose fluctuations in live brain tissue using background-subtracted, fast-scan cyclic voltammetry. The novel microbiosensor consists of a simple carbon fiber surface modified with an electrodeposited chitosan hydrogel encapsulating glucose oxidase. The selectivity afforded by voltammetry enables quantitative and qualitative measurements of enzymatically generated H2O2 without the need for additional strategies to eliminate interfering agents. The microbiosensors possess a sensitivity and limit of detection for glucose of 19.4 ± 0.2 nA mM(-1) and 13.1 ± 0.7 μM, respectively. They are stable, even under deviations from physiological normoxic conditions, and show minimal interference from endogenous electroactive substances. Using this approach, we have quantitatively and selectively monitored pharmacologically evoked glucose fluctuations with unprecedented chemical and spatial resolution. Furthermore, this novel biosensing strategy is widely applicable to the immobilization of any H2O2 producing enzyme, enabling rapid monitoring of many nonelectroactive enzyme substrates.

  18. Computational diagnosis of protein conformational diseases: short molecular dynamics simulations reveal a fast unfolding of r-LDL mutants that cause familial hypercholesterolemia.

    PubMed

    Cuesta-López, S; Falo, F; Sancho, J

    2007-01-01

    The molecular basis of conformational diseases frequently resides in mutant proteins constituting a subset of the vast mutational space. While the subtleties of protein structure point to molecular dynamics (MD) techniques as promising tools for an efficient exploration of such a space, the average size of proteins and the time scale of unfolding events make this goal difficult with present computational capabilities. We show here, nevertheless, that an efficient approach is already feasible for modular proteins. Familial hypercholesterolemia (FH) is a conformational disease linked to mutations in the gene encoding the low density lipoprotein receptor. A high percentage of these mutations has been found in the seven small modular binding repeats of the receptor. Taking advantage of its small size, we have performed an in depth MD study of the fifth binding repeat. Fast unfolding dynamics have been observed in the absence of a structural bound calcium ion, which agrees with its reported essential role in the stability of the module. In addition, several mutations detected in FH patients have been analyzed, starting from the native conformation. Our results indicate that in contrast with the wild type protein and an innocuous control mutant, disease-related mutants experience, in short simulation times (2-8 ns), gross departures from the native state that lead to unfolded conformations and, in some cases, to binding site desorganization deriving in calcium release. Computational diagnosis of mutations leading to conformational diseases seems thus feasible, at least for small or modular pathogenic proteins.

  19. FAST TRACK COMMUNICATION: Femtosecond isomerization dynamics in the ethylene cation measured in an EUV-pump NIR-probe configuration

    NASA Astrophysics Data System (ADS)

    Tilborg, J. van; Allison, T. K.; Wright, T. W.; Hertlein, M. P.; Falcone, R. W.; Liu, Y.; Merdji, H.; Belkacem, A.

    2009-04-01

    Dynamics in the excited ethylene cation C2H+4 lead to isomerization to the ethylidene configuration (HC-CH3)+, which is predicted to be a transient configuration for electronic relaxation. With an intense femtosecond extreme ultraviolet pump pulse to populate the excited state, and a near infrared probe pulse to produce the fragments CH+ and CH+3 (which provides a direct signature of ethylidene), we measure optimum fragment yields at a probe delay of 80 fs. Also, an H2-stretch transient configuration, yielding H+2 upon probing, is found to succeed the ethylidene configuration. We find that a simple single- or double-decay model does not match the data, and we present a modified model (introduction of an isomerization delay of 50 ± 25 fs) that does provide agreement.

  20. MALDI-TOF Mass Spectrometry Enables a Comprehensive and Fast Analysis of Dynamics and Qualities of Stress Responses of Lactobacillus paracasei subsp. paracasei F19

    PubMed Central

    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

  1. FeynDyn: A MATLAB program for fast numerical Feynman integral calculations for open quantum system dynamics on GPUs

    NASA Astrophysics Data System (ADS)

    Dattani, Nikesh S.

    2013-12-01

    This MATLAB program calculates the dynamics of the reduced density matrix of an open quantum system modeled either by the Feynman-Vernon model or the Caldeira-Leggett model. The user gives the program a Hamiltonian matrix that describes the open quantum system as if it were in isolation, a matrix of the same size that describes how that system couples to its environment, and a spectral distribution function and temperature describing the environment’s influence on it, in addition to the open quantum system’s initial density matrix and a grid of times. With this, the program returns the reduced density matrix of the open quantum system at all moments specified by that grid of times (or just the last moment specified by the grid of times if the user makes this choice). This overall calculation can be divided into two stages: the setup of the Feynman integral, and the actual calculation of the Feynman integral for time propagation of the density matrix. When this program calculates this propagation on a multi-core CPU, it is this propagation that is usually the rate-limiting step of the calculation, but when it is calculated on a GPU, the propagation is calculated so quickly that the setup of the Feynman integral can actually become the rate-limiting step. The overhead of transferring information from the CPU to the GPU and back seems to have a negligible effect on the overall runtime of the program. When the required information cannot fit on the GPU, the user can choose to run the entire program on a CPU. Catalogue identifier: AEPX_v1_0. Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEPX_v1_0.html. Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland. Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html. No. of lines in distributed program, including test data, etc.: 703. No. of bytes in distributed program, including test data, etc.: 11026. Distribution format: tar.gz. Programming

  2. Development of hardware accelerator for molecular dynamics simulations: a computation board that calculates nonbonded interactions in cooperation with fast multipole method.

    PubMed

    Amisaki, Takashi; Toyoda, Shinjiro; Miyagawa, Hiroh; Kitamura, Kunihiro

    2003-04-15

    Evaluation of long-range Coulombic interactions still represents a bottleneck in the molecular dynamics (MD) simulations of biological macromolecules. Despite the advent of sophisticated fast algorithms, such as the fast multipole method (FMM), accurate simulations still demand a great amount of computation time due to the accuracy/speed trade-off inherently involved in these algorithms. Unless higher order multipole expansions, which are extremely expensive to evaluate, are employed, a large amount of the execution time is still spent in directly calculating particle-particle interactions within the nearby region of each particle. To reduce this execution time for pair interactions, we developed a computation unit (board), called MD-Engine II, that calculates nonbonded pairwise interactions using a specially designed hardware. Four custom arithmetic-processors and a processor for memory manipulation ("particle processor") are mounted on the computation board. The arithmetic processors are responsible for calculation of the pair interactions. The particle processor plays a central role in realizing efficient cooperation with the FMM. The results of a series of 50-ps MD simulations of a protein-water system (50,764 atoms) indicated that a more stringent setting of accuracy in FMM computation, compared with those previously reported, was required for accurate simulations over long time periods. Such a level of accuracy was efficiently achieved using the cooperative calculations of the FMM and MD-Engine II. On an Alpha 21264 PC, the FMM computation at a moderate but tolerable level of accuracy was accelerated by a factor of 16.0 using three boards. At a high level of accuracy, the cooperative calculation achieved a 22.7-fold acceleration over the corresponding conventional FMM calculation. In the cooperative calculations of the FMM and MD-Engine II, it was possible to achieve more accurate computation at a comparable execution time by incorporating larger nearby

  3. Molecular dynamics simulation of polymerlike thin films irradiated by fast ions: A comparison between FENE and Lennard-Jones potentials

    NASA Astrophysics Data System (ADS)

    Lima, N. W.; Gutierres, L. I.; Gonzalez, R. I.; Müller, S.; Thomaz, R. S.; Bringa, E. M.; Papaléo, R. M.

    2016-11-01

    In this paper, the surface effects of individual heavy ions impacting thin polymerlike films were investigated, using molecular dynamics simulations with the finite extensible nonlinear elastic (FENE) potential to describe the molecular chains. The perturbation introduced by the ions in the lattice was modeled assuming that the initial excitation energy in the ion track is converted into an effective temperature, as in a thermal spike. The track was heated only within the film thickness h , leaving a nonexcited substrate below. The effect of decreasing thickness on cratering and sputtering was evaluated. The results were compared to experimental data of thin polymer films bombarded by MeV-GeV ions and to simulations performed with the Lennard-Jones potential. While several qualitative results observed in the experiments were also seen in the simulations, irrespective of the potential used, there are important differences observed on FENE films. Crater dimensions, rim volume, and sputtering yields are substantially reduced, and a threshold thickness for molecular ejection appears in FENE simulations. This is attributed to the additional restrictions on mass transport out of the excited track region imposed by interchain interactions (entanglements) and by the low mobility of the molten phase induced by the spike.

  4. IAS15: a fast, adaptive, high-order integrator for gravitational dynamics, accurate to machine precision over a billion orbits

    NASA Astrophysics Data System (ADS)

    Rein, Hanno; Spiegel, David S.

    2015-01-01

    We present IAS15, a 15th-order integrator to simulate gravitational dynamics. The integrator is based on a Gauß-Radau quadrature and can handle conservative as well as non-conservative forces. We develop a step-size control that can automatically choose an optimal timestep. The algorithm can handle close encounters and high-eccentricity orbits. The systematic errors are kept well below machine precision, and long-term orbit integrations over 109 orbits show that IAS15 is optimal in the sense that it follows Brouwer's law, i.e. the energy error behaves like a random walk. Our tests show that IAS15 is superior to a mixed-variable symplectic integrator and other popular integrators, including high-order ones, in both speed and accuracy. In fact, IAS15 preserves the symplecticity of Hamiltonian systems better than the commonly used nominally symplectic integrators to which we compared it. We provide an open-source implementation of IAS15. The package comes with several easy-to-extend examples involving resonant planetary systems, Kozai-Lidov cycles, close encounters, radiation pressure, quadrupole moment and generic damping functions that can, among other things, be used to simulate planet-disc interactions. Other non-conservative forces can be added easily.

  5. A fast predicting neural fuzzy model for on-line estimation of nutrient dynamics in an anoxic/oxic process.

    PubMed

    Huang, Ming-zhi; Wan, Jin-quan; Ma, Yong-wen; Li, Wei-jiang; Sun, Xiao-fei; Wan, Yan

    2010-03-01

    In this paper a software sensor based on a fuzzy neural network approach was proposed for real-time estimation of nutrient concentrations. In order to improve the network performance, fuzzy subtractive clustering was used to identify model architecture, extract and optimize fuzzy rule of the model. A split network structure was applied separately for anaerobic and aerobic conditions was employed with dynamic modeling methods such as autoregressive with exogenous inputs and multi-way principal component analysis (MPCA). The proposed methodology was applied to a bench-scale anoxic/oxic process for biological nitrogen removal. The simulative results indicate that the learning ability and generalization of the model performed well and also worked well for normal batch operations corresponding to three data points inside the confidence limit determined by MPCA. Real-time estimation of NO(3)(-), NH(4)(+) and PO(4)(3-) concentration based on fuzzy neural network analysis were successfully carried out with the simple on-line information regarding the anoxic/oxic system.

  6. Two Binding Geometries for Risperidone in Dopamine D3 Receptors: Insights on the Fast-Off Mechanism through Docking, Quantum Biochemistry, and Molecular Dynamics Simulations.

    PubMed

    Zanatta, Geancarlo; Della Flora Nunes, Gustavo; Bezerra, Eveline M; da Costa, Roner F; Martins, Alice; Caetano, Ewerton W S; Freire, Valder N; Gottfried, Carmem

    2016-10-19

    Risperidone is an atypical antipsychotic used in the treatment of schizophrenia and of symptoms of irritability associated with autism spectrum disorder (ASD). Its main action mechanism is the blockade of D2-like receptors acting over positive and negative symptoms of schizophrenia with small risk of extrapyramidal symptoms (EPS) at doses corresponding to low/moderate D2 occupancy. Such a decrease in the side effect incidence can be associated with its fast unbinding from D2 receptors in the nigrostriatal region allowing the recovery of dopamine signaling pathways. We performed docking essays using risperidone and the D3 receptor crystallographic data and results suggested two possible distinct orientations for risperidone at the binding pocket. Orientation 1 is more close to the opening of the binding site and has the 6-fluoro-1,2 benzoxazole fragment toward the bottom of the D3 receptor cleft, while orientation 2 is deeper inside the binding pocket with the same fragment toward to the receptor surface. In order to unveil the implications of these two binding orientations, classical molecular dynamics and quantum biochemistry computations within the density functional theory formalism and the molecular fractionation with conjugate caps framework were performed. Quantum mechanics/molecular mechanics suggests that orientation 2 (considering the contribution of Glu90) is slightly more energetically stable than orientation 1 with the main contribution coming from residue Asp110. The residue Glu90, positioned at the opening of the binding site, is closer to orientation 1 than 2, suggesting that it may have a key role in stability through attractive interaction with risperidone. Therefore, although orientations 1 and 2 are both likely to occur, we suggest that the occurrence of the first may contribute to the reduction of side effects in patients taking risperidone due to the reduction of dopamine receptor occupancy in the nigrostriatal region through a mechanism of

  7. Dynamics of the Emission Spectrum of a Single LH2 Complex: Interplay of Slow and Fast Nuclear Motions

    PubMed Central

    Novoderezhkin, Vladimir I.; Rutkauskas, Danielis; van Grondelle, Rienk

    2006-01-01

    We have studied the relationship between the realizations of static disorder and the emission spectra observed for a single LH2 complex. We show that the experimentally observed spectral fluctuations reflect realizations of the disorder in the B850 ring associated with different degrees of exciton delocalization and different effective coupling of the excitons to phonon modes. The main spectral features cannot be explained using models with correlated disorder associated with elliptical deformations of the ring. A quantitative explanation of the measured single-molecule spectra is obtained using the modified Redfield theory and a model of the B850 ring with uncorrelated disorder of the site energies. The positions and spectral shapes of the main exciton components in this model are determined by the disorder-induced shift of exciton eigenvalues in combination with phonon-induced effects (i.e., reorganization shift and broadening, that increase in proportion to the inverse delocalization length of the exciton state). Being dependent on the realization of the disorder, these factors produce different forms of the emission profile. In addition, the different degree of delocalization and effective couplings to phonons determines a different type of excitation dynamics for each of these realizations. We demonstrate that experimentally observed quasistable conformational states are characterized by excitation energy transfer regimes varying from a coherent wavelike motion of a delocalized exciton (with a 100-fs pass over half of the ring) to a hopping-type motion of the wavepacket (with a 350-fs jump between separated groups of 3–4 molecules) and self-trapped excitations that do not move from their localization site. PMID:16443651

  8. The Tofts model in frequency domain: fast and robust determination of pharmacokinetic maps for dynamic contrast enhancement MRI

    NASA Astrophysics Data System (ADS)

    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.

  9. Fast effects of biochar amendment on soil C and N dynamics, nutrient availability and fertility under controlled conditions

    NASA Astrophysics Data System (ADS)

    De la Rosa, J. M.; Knicker, H.

    2012-04-01

    The shift towards a biobased economy will probably trigger the application of bioenergy by-products and charred residues to the soil as either amendments or fertilizers. However, limited research has been done to determine how this will influence C and N dynamics and soil functioning. The aim of this work was to investigate the effects of 15N enriched pyrogenic organic matter (15N-PyOM) on C and N mineralisation, nutrient availability and fertility of amended soil. A typical Andalusian agricultural soil (calcareous Rhodoxeralf) was amended (0.1% w/w) with 15N enriched-biochar produced from Lolium perenne. The bioavailability and partitioning of the 15N from the biochars was tested by determining its content in the soil and the ray grass grown on this soil under controlled conditions for 72 days. After 30, 60 and 72 days of incubation, soil samples were analyzed for C, N, 15N, microbial biomass C. In addition, the chemical alteration of the 15N-containing organic structures during mobilization/immobilization was followed by solid-state 15N NMR spectroscopy. Soil amendment led to a general increase in the biomass production and N retention. After 72 days of incubation, 10 % of the 15N added in the soil with the PyOM had been degraded and available for grass growth. 15N and 13C NMR spectra confirmed that part of the pyrogenic heterocyclic N has been transformed into amide N, possibly by the use of microbiologically mobilized 15N from the char. Newer results indicate that PyOM can be microbially degraded, the efficiency of which depends on its chemical composition and properties. The chemical properties of the used material as well as the optimal conditions for microbial decay during the laboratory incubation experiments are likely to have augmented PyOM decomposition. In summary, our results indicate that: i) a re-evaluation of the potential of pyrogenic material as a sink of C and N is needed. ii) the characterization of the chemical composition of char material is

  10. Lipid metabolism during fasting.

    PubMed

    Jensen, M D; Ekberg, K; Landau, B R

    2001-10-01

    These studies were conducted to understand the relationship between measures of systemic free fatty acid (FFA) reesterification and regional FFA, glycerol, and triglyceride metabolism during fasting. Indirect calorimetry was used to measure fatty acid oxidation in six men after a 60-h fast. Systemic and regional (splanchnic, renal, and leg) FFA ([(3)H]palmitate) and glycerol ([(3)H]glycerol) kinetics, as well as splanchnic triglyceride release, were measured. The rate of systemic FFA reesterification was 366 +/- 93 micromol/min, which was greater (P < 0.05) than splanchnic triglyceride fatty acid output (64 +/- 6 micromol/min), a measure of VLDL triglyceride fatty acid export. The majority of glycerol uptake occurred in the splanchnic and renal beds, although some leg glycerol uptake was detected. Systemic FFA release was approximately double that usually present in overnight postabsorptive men, yet the regional FFA release rates were of the same proportions previously observed in overnight postabsorptive men. In conclusion, FFA reesterification at rest during fasting far exceeds splanchnic triglyceride fatty acid output. This indicates that nonhepatic sites of FFA reesterification are important, and that peripheral reesterification of FFA exceeds the rate of simultaneous intracellular triglyceride fatty acid oxidation.

  11. Modeling spontaneous activity in the developing spinal cord using activity-dependent variations of intracellular chloride.

    PubMed

    Marchetti, Cristina; Tabak, Joel; Chub, Nikolai; O'Donovan, Michael J; Rinzel, John

    2005-04-06

    We investigated how spontaneous activity is generated in developing, hyperexcitable networks. We focused our study on the embryonic chick spinal cord, a preparation that exhibits rhythmic discharge on multiple timescales: slow episodes (lasting minutes) and faster intraepisode cycling (approximately 1 Hz frequency). For this purpose, we developed a mean field model of a recurrent network with slow chloride dynamics and a fast depression variable. We showed that the model, in addition to providing a biophysical mechanism for the slow dynamics, was able to account for the experimentally observed activity. The model made predictions on how interval and duration of episodes are affected when changing chloride-mediated synaptic transmission or chloride flux across cell membrane. These predictions guided experiments, and the model results were compared with experimental data obtained with electrophysiological recordings. We found agreement when transmission was affected through changes in synaptic conductance and good qualitative agreement when chloride flux was varied through changes in external chloride concentration or in the rate of the Na+-K+-2Cl- cotransporter. Furthermore, the model made predictions about the time course of intracellular chloride concentration and chloride reversal potential and how these are affected by changes in synaptic conductance. Based on the comparison between modeling and experimental results, we propose that chloride dynamics could be an important mechanism in rhythm generation in the developing chick spinal cord.

  12. Recent advances in experimental techniques to probe fast excited-state dynamics in biological molecules in the gas phase: dynamics in nucleotides, amino acids and beyond

    PubMed Central

    Staniforth, Michael; Stavros, Vasilios G.

    2013-01-01

    In many chemical reactions, an activation barrier must be overcome before a chemical transformation can occur. As such, understanding the behaviour of molecules in energetically excited states is critical to understanding the chemical changes that these molecules undergo. Among the most prominent reactions for mankind to understand are chemical changes that occur in our own biological molecules. A notable example is the focus towards understanding the interaction of DNA with ultraviolet radiation and the subsequent chemical changes. However, the interaction of radiation with large biological structures is highly complex, and thus the photochemistry of these systems as a whole is poorly understood. Studying the gas-phase spectroscopy and ultrafast dynamics of the building blocks of these more complex biomolecules offers the tantalizing prospect of providing a scientifically intuitive bottom-up approach, beginning with the study of the subunits of large polymeric biomolecules and monitoring the evolution in photochemistry as the complexity of the molecules is increased. While highly attractive, one of the main challenges of this approach is in transferring large, and in many cases, thermally labile molecules into vacuum. This review discusses the recent advances in cutting-edge experimental methodologies, emerging as excellent candidates for progressing this bottom-up approach. PMID:24204191

  13. A dynamic system for the simulation of fasting luminal pH-gradients using hydrogen carbonate buffers for dissolution testing of ionisable compounds.

    PubMed

    Garbacz, Grzegorz; Kołodziej, Bartosz; Koziolek, Mirko; Weitschies, Werner; Klein, Sandra

    2014-01-23

    The hydrogen carbonate buffer is considered as the most biorelevant buffer system for the simulation of intestinal conditions and covers the physiological pH range of the luminal fluids from pH 5.5 to about pH 8.4. The pH value of a hydrogen carbonate buffer is the result of a complex and dynamic interplay of the concentration of hydrogen carbonate ions, carbonic acid, the concentration of dissolved and solvated carbon dioxide and its partial pressure above the solution. The complex equilibrium between the different ions results in a thermodynamic instability of hydrogen carbonate solutions. In order to use hydrogen carbonate buffers with pH gradients in the physiological range and with the dynamics observed in vivo without changing the ionic strength of the solution, we developed a device (pHysio-grad®) that provides both acidification of the dissolution medium by microcomputer controlled carbon dioxide influx and alkalisation by degassing. This enables a continuous pH control and adjustment during dissolution of ionisable compounds. The results of the pH adjustment indicate that the system can compensate even rapid pH changes after addition of a basic or acidic moiety in amounts corresponding up to 90% of the overall buffer capacity. The results of the dissolution tests performed for a model formulation containing ionizable compounds (Nexium 20mg mups) indicate that both the simulated fasting intraluminal pH-profiles and the buffer species can significantly affect the dissolution process by changing the lag time prior to initial drug release and the release rate of the model compound. A prediction of the in vivo release behaviour of this formulation is thus most likely strongly related to the test conditions such as pH and buffer species.

  14. Fast Domain Partitioning Method for dynamic boundary integral equations applicable to non-planar faults dipping in 3-D elastic half-space

    NASA Astrophysics Data System (ADS)

    Ando, Ryosuke

    2016-11-01

    The elastodynamic boundary integral equation method (BIEM) in real space and in the temporal domain is an accurate semi-analytical tool to investigate the earthquake rupture dynamics on non-planar faults. However, its heavy computational demand for a historic integral generally increases with a time complexity of O(MN3)for the number of time steps N and elements M due to volume integration in the causality cone. In this study, we introduce an efficient BIEM, termed the `Fast Domain Partitioning Method' (FDPM), which enables us to reduce the computation time to the order of the surface integral, O(MN2), without degrading the accuracy. The memory requirement is also reduced to O(M2) from O(M2N). FDPM uses the physical nature of Green's function for stress to partition the causality cone into the domains of the P and S wave fronts, the domain in-between the P and S wave fronts, and the domain of the static equilibrium, where the latter two domains exhibit simpler dependences on time and/or space. The scalability of this method is demonstrated on the large-scale parallel computing environments of distributed memory systems. It is also shown that FDPM enables an efficient use of memory storage, which makes it possible to reduce computation times to a previously unprecedented level. We thus present FDPM as a powerful tool to break through the current fundamental difficulties in running dynamic simulations of coseismic ruptures and earthquake cycles under realistic conditions of fault geometries.

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

    NASA Astrophysics Data System (ADS)

    Chen, J.; Zhuang, G.; Li, Q.; Liu, Y.; Gao, L.; Zhou, Y. N.; Jian, X.; Xiong, C. Y.; Wang, Z. J.; Brower, D. L.; Ding, W. X.

    2014-11-01

    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.

  16. Fast CRCs

    DTIC Science & Technology

    2009-10-01

    Detecting Codes: General Theory and Their Application in Feedback Communication Systems. Kluwer Academic, 1995. [8] D.E. Knuth , The Art of Computer ... computation . Index Terms—Fast CRC, low-complexity CRC, checksum, error-detection code, Hamming code, period of polynomial, fast software implementation...simulations, and performance analysis of systems and networks. CRC implementation in software is desirable, because many computers do not have hardware

  17. Ring polymer molecular dynamics fast computation of rate coefficients on accurate potential energy surfaces in local configuration space: Application to the abstraction of hydrogen from methane.

    PubMed

    Meng, Qingyong; Chen, Jun; Zhang, Dong H

    2016-04-21

    To fast and accurately compute rate coefficients of the H/D + CH4 → H2/HD + CH3reactions, we propose a segmented strategy for fitting suitable potential energy surface (PES), on which ring-polymer molecular dynamics (RPMD) simulations are performed. On the basis of recently developed permutation invariant polynomial neural-network approach [J. Li et al., J. Chem. Phys. 142, 204302 (2015)], PESs in local configuration spaces are constructed. In this strategy, global PES is divided into three parts, including asymptotic, intermediate, and interaction parts, along the reaction coordinate. Since less fitting parameters are involved in the local PESs, the computational efficiency for operating the PES routine is largely enhanced by a factor of ∼20, comparing with that for global PES. On interaction part, the RPMD computational time for the transmission coefficient can be further efficiently reduced by cutting off the redundant part of the child trajectories. For H + CH4, good agreements among the present RPMD rates and those from previous simulations as well as experimental results are found. For D + CH4, on the other hand, qualitative agreement between present RPMD and experimental results is predicted.

  18. Ring polymer molecular dynamics fast computation of rate coefficients on accurate potential energy surfaces in local configuration space: Application to the abstraction of hydrogen from methane

    NASA Astrophysics Data System (ADS)

    Meng, Qingyong; Chen, Jun; Zhang, Dong H.

    2016-04-01

    To fast and accurately compute rate coefficients of the H/D + CH4 → H2/HD + CH3 reactions, we propose a segmented strategy for fitting suitable potential energy surface (PES), on which ring-polymer molecular dynamics (RPMD) simulations are performed. On the basis of recently developed permutation invariant polynomial neural-network approach [J. Li et al., J. Chem. Phys. 142, 204302 (2015)], PESs in local configuration spaces are constructed. In this strategy, global PES is divided into three parts, including asymptotic, intermediate, and interaction parts, along the reaction coordinate. Since less fitting parameters are involved in the local PESs, the computational efficiency for operating the PES routine is largely enhanced by a factor of ˜20, comparing with that for global PES. On interaction part, the RPMD computational time for the transmission coefficient can be further efficiently reduced by cutting off the redundant part of the child trajectories. For H + CH4, good agreements among the present RPMD rates and those from previous simulations as well as experimental results are found. For D + CH4, on the other hand, qualitative agreement between present RPMD and experimental results is predicted.

  19. Computational Fluid Dynamics Simulation of Hydrodynamics and Stresses in the PhEur/USP Disintegration Tester Under Fed and Fasted Fluid Characteristics.

    PubMed

    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.

  20. Evaluation of the aero-optical properties of the SOFIA cavity by means of computional fluid dynamics and a super fast diagnostic camera

    NASA Astrophysics Data System (ADS)

    Engfer, Christian; Pfüller, Enrico; Wiedemann, Manuel; Wolf, Jürgen; Lutz, Thorsten; Krämer, Ewald; Röser, Hans-Peter

    2012-09-01

    The Stratospheric Observatory for Infrared Astronomy (SOFIA) is a 2.5 m reflecting telescope housed in an open cavity on board of a Boeing 747SP. During observations, the cavity is exposed to transonic flow conditions. The oncoming boundary layer evolves into a free shear layer being responsible for optical aberrations and for aerodynamic and aeroacoustic disturbances within the cavity. While the aero-acoustical excitation of an airborne telescope can be minimized by using passive flow control devices, the aero-optical properties of the flow are difficult to improve. Hence it is important to know how much the image seen through the SOFIA telescope is perturbed by so called seeing effects. Prior to the SOFIA science fights Computational Fluid Dynamics (CFD) simulations using URANS and DES methods were carried out to determine the flow field within and above the cavity and hence in the optical path in order to provide an assessment of the aero-optical properties under baseline conditions. In addition and for validation purposes, out of focus images have been taken during flight with a Super Fast Diagnostic Camera (SFDC). Depending on the binning factor and the sub-array size, the SFDC is able to take and to read out images at very high frame rates. The paper explains the numerical approach based on CFD to evaluate the aero-optical properties of SOFIA. The CFD data is then compared to the high speed images taken by the SFDC during flight.

  1. Intracellular Signalling in Retinal Ischemia

    DTIC Science & Technology

    1990-07-01

    36) However, vascularization of the RPE is not known to occur in human diseases of photoreceptor degeneration, such as retinitis pigmentosa ...A.C. (1986) Retinitis pigmentosa and retinal neovascularization. Ophthalmology 91, 1599- 1603. Figure la: Control rat retina, 8 weeks of age, central...TITLE (Include Security Classification) Intracellular Signalling in Retinal Ischemia 12. PERSONAL AUTHOR(S) Burns, Margaret Sue; Bellhorn, Roy William

  2. Direct Measurement of Intracellular Pressure

    PubMed Central

    Petrie, Ryan J.; Koo, Hyun

    2014-01-01

    A method to directly measure the intracellular pressure of adherent, migrating cells is described in the Basic Protocol. This approach is based on the servo-null method where a microelectrode is introduced into the cell to directly measure the physical pressure of the cytoplasm. We also describe the initial calibration of the microelectrode as well as the application of the method to cells migrating inside three-dimensional (3D) extracellular matrix (ECM). PMID:24894836

  3. Revisiting intracellular calcium signaling semantics.

    PubMed

    Haiech, Jacques; Audran, Emilie; Fève, Marie; Ranjeva, Raoul; Kilhoffer, Marie-Claude

    2011-12-01

    Cells use intracellular free calcium concentration changes for signaling. Signal encoding occurs through both spatial and temporal modulation of the free calcium concentration. The encoded message is detected by an ensemble of intracellular sensors forming the family of calcium-binding proteins (CaBPs) which must faithfully translate the message using a new syntax that is recognized by the cell. The cell is home to a significant although limited number of genes coding for proteins involved in the signal encoding and decoding processes. In a cell, only a subset of this ensemble of genes is expressed, leading to a genetic regulation of the calcium signal pathways. Calmodulin (CaM), the most ubiquitous expressed intracellular calcium-binding protein, plays a major role in calcium signal translation. Similar to a hub, it is central to a large and finely tuned network, receiving information, integrating it and dispatching the cognate response. In this review, we examine the different steps starting with an external stimulus up to a cellular response, with special emphasis on CaM and the mechanism by which it decodes calcium signals and translates it into exquisitely coordinated cellular events. By this means, we will revisit the calcium signaling semantics, hoping that we will ease communication between scientists dealing with calcium signals in different biological systems and different domains.

  4. Stochastic models of intracellular transport

    NASA Astrophysics Data System (ADS)

    Bressloff, Paul C.; Newby, Jay M.

    2013-01-01

    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.

  5. Number and brightness analysis of sFRP4 domains in live cells demonstrates vesicle association signal of the NLD domain and dynamic intracellular responses to Wnt3a

    PubMed Central

    Perumal, Vanathi; Krishnan, Kannan; Gratton, Enrico; Dharmarajan, Arun M; Fox, Simon A

    2015-01-01

    The Wnts are secreted, lipidated glycoproteins that play a role in cellular processes of differentiation, proliferation, migration, survival, polarity and stem cell self-renewal. The majority of Wnts biological effects are through binding to specific frizzled (Fzd) receptor complexes leading to activation of downstream pathways. Secreted Frizzled-related proteins (sFRPs) were first identified as antagonists of Wnt signalling by binding directly to Wnts. They comprise two domains, a Fzd-like cysteine rich domain (CRD) and a netrin-like domain (NLD). Subsequently sFRPs have been shown to also interact with Fzd receptors and more diverse functions have been identified, including potentiation of Wnt signalling. Many aspects of the biology of this family remain to be elucidated. We used the number and brightness (N&B) method, a technique based on fluorescence fluctuation analysis, to characterise the intracellular aggregation and trafficking of sFRP4 domains. We expressed sFRP4 and its’ domains as EGFP fusions and then characterised the effect of endogenous Wnt3a by fluorescence confocal imaging. We observed vesicular trafficking of sFRP4 and that the NLD domain has a vesicular association signal. We found that sFRP4 and the CRD formed oligomeric aggregates in the perinuclear region while the NLD was distributed evenly throughout the cell with a larger proportion of aggregates. Most significantly we observed intracellular redistribution of sFRP4 in response to Wnt3a suggesting that Wnt3a can modulate intracellular localisation and secretion of sFRP4. Our results reveal a number of novel findings regarding sFRP4 which are likely to have relevance to this wider family. PMID:25805505

  6. Oscillating optical tweezer-based 3-D confocal microrheometer for investigating the intracellular micromechanics and structures

    NASA Astrophysics Data System (ADS)

    Ou-Yang, H. D.; Rickter, E. A.; Pu, C.; Latinovic, O.; Kumar, A.; Mengistu, M.; Lowe-Krentz, L.; Chien, S.

    2005-08-01

    Mechanical properties of living biological cells are important for cells to maintain their shapes, support mechanical stresses and move through tissue matrix. The use of optical tweezers to measure micromechanical properties of cells has recently made significant progresses. This paper presents a new approach, the oscillating optical tweezer cytorheometer (OOTC), which takes advantage of the coherent detection of harmonically modulated particle motions by a lock-in amplifier to increase sensitivity, temporal resolution and simplicity. We demonstrate that OOTC can measure the dynamic mechanical modulus in the frequency range of 0.1-6,000 Hz at a rate as fast as 1 data point per second with submicron spatial resolution. More importantly, OOTC is capable of distinguishing the intrinsic non-random temporal variations from random fluctuations due to Brownian motion; this capability, not achievable by conventional approaches, is particular useful because living systems are highly dynamic and often exhibit non-thermal, rhythmic behavior in a broad time scale from a fraction of a second to hours or days. Although OOTC is effective in measuring the intracellular micromechanical properties, unless we can visualize the cytoskeleton in situ, the mechanical property data would only be as informative as that of "Blind men and the Elephant". To solve this problem, we take two steps, the first, to use of fluorescent imaging to identify the granular structures trapped by optical tweezers, and second, to integrate OOTC with 3-D confocal microscopy so we can take simultaneous, in situ measurements of the micromechanics and intracellular structure in living cells. In this paper, we discuss examples of applying the oscillating tweezer-based cytorheometer for investigating cultured bovine endothelial cells, the identification of caveolae as some of the granular structures in the cell as well as our approach to integrate optical tweezers with a spinning disk confocal microscope.

  7. Exploring Anti-Bacterial Compounds against Intracellular Legionella

    PubMed Central

    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 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. PMID:24058631

  8. Fast valve

    DOEpatents

    Van Dyke, W.J.

    1992-04-07

    A fast valve is disclosed that can close on the order of 7 milliseconds. It is closed by the force of a compressed air spring with the moving parts of the valve designed to be of very light weight and the valve gate being of wedge shaped with O-ring sealed faces to provide sealing contact without metal to metal contact. The combination of the O-ring seal and an air cushion create a soft final movement of the valve closure to prevent the fast air acting valve from having a harsh closing. 4 figs.

  9. Fast valve

    DOEpatents

    Van Dyke, William J.

    1992-01-01

    A fast valve is disclosed that can close on the order of 7 milliseconds. It is closed by the force of a compressed air spring with the moving parts of the valve designed to be of very light weight and the valve gate being of wedge shaped with O-ring sealed faces to provide sealing contact without metal to metal contact. The combination of the O-ring seal and an air cushion create a soft final movement of the valve closure to prevent the fast air acting valve from having a harsh closing.

  10. Intracellular targeting with engineered proteins

    PubMed Central

    Miersch, Shane; Sidhu, Sachdev S.

    2016-01-01

    If the isolation, production, and clinical use of insulin marked the inception of the age of biologics as therapeutics, the convergence of molecular biology and combinatorial engineering techniques marked its coming of age. The first wave of recombinant protein-based drugs in the 1980s demonstrated emphatically that proteins could be engineered, formulated, and employed for clinical advantage. Yet despite the successes of protein-based drugs such as antibodies, enzymes, and cytokines, the druggable target space for biologics is currently restricted to targets outside the cell. Insofar as estimates place the number of proteins either secreted or with extracellular domains in the range of 8000 to 9000, this represents only one-third of the proteome and circumscribes the pathways that can be targeted for therapeutic intervention. Clearly, a major objective for this field to reach maturity is to access, interrogate, and modulate the majority of proteins found inside the cell. However, owing to the large size, complex architecture, and general cellular impermeability of existing protein-based drugs, this poses a daunting challenge. In recent years, though, advances on the two related fronts of protein engineering and drug delivery are beginning to bring this goal within reach. First, prompted by the restrictions that limit the applicability of antibodies, intense efforts have been applied to identifying and engineering smaller alternative protein scaffolds for the modulation of intracellular targets. In parallel, innovative solutions for delivering proteins to the intracellular space while maintaining their stability and functional activity have begun to yield successes. This review provides an overview of bioactive intrabodies and alternative protein scaffolds amenable to engineering for intracellular targeting and also outlines advances in protein engineering and formulation for delivery of functional proteins to the interior of the cell to achieve therapeutic action

  11. Pharmacology of intracellular signalling pathways

    PubMed Central

    Nahorski, Stefan R

    2006-01-01

    This article provides a brief and somewhat personalized review of the dramatic developments that have occurred over the last 45 years in our understanding of intracellular signalling pathways associated with G-protein-coupled receptor activation. Signalling via cyclic AMP, the phosphoinositides and Ca2+ is emphasized and these systems have already been revealed as new pharmacological targets. The therapeutic benefits of most of such targets are, however, yet to be realized, but it is certain that the discipline of pharmacology needs to widen its boundaries to meet these challenges in the future. PMID:16402119

  12. Time-resolved study of the extreme-ultraviolet emission and plasma dynamics of a sub-Joule, fast capillary discharge

    NASA Astrophysics Data System (ADS)

    Valenzuela, J. C.; Wyndham, E. S.; Favre, M.

    2015-08-01

    In this work, we discuss experimental observations on the dynamics of a fast, low energy capillary discharge when operated in argon and its properties as an intense source of extreme-ultraviolet (EUV) radiation. The discharge pre-ionization and self-triggering were accomplished by the use of the hollow cathode effect. This allowed a compact size and low inductance discharge with multi-kA current level and a quarter-period of ˜10 ns at sub-Joule energy level. We used the novel moiré and schlieren diagnostics with a 12 ps laser to obtain the time evolution of the line electron density and to study the plasma dynamics. EUV spectroscopy and filtered diodes were also implemented to estimate the plasma temperature and density throughout the evolution of the discharge. EUV source size was measured by using a filtered slit-wire camera. We observed that EUV emission starts from a compressed plasma on axis during the second quarter-period of the current and continues until the fifth quarter-period. Ionization levels from Ar VII to X were observed. By comparing the EUV emission spectra with synthetic spectra, we found that at the onset of emission (˜7 ns), the plasma is well fitted by a single Maxwellian electron distribution function with Te ˜ 12 eV and ne ˜ 1017 cm-3. Close to peak emission (˜13 ns), plasma temperature and density increase to ˜20 eV and ne ˜ 1018 cm-3, respectively. However, in order to successfully match the experimental data, a two component electron distribution function was necessary. Later in time, a smaller fraction in the high energy component and higher temperature suggests homogenization of the plasma. The moiré and schlieren diagnostics showed multiple radial compression-waves merging on axis throughout the discharge; they are an important heating mechanism that leads to a period of severe turbulence at peak EUV emission. It was also observed that emission ceases when the axial maximum of the electron density collapses.

  13. Fast Li ion dynamics in the solid electrolyte Li7 P3 S11 as probed by (6,7) Li NMR spin-lattice relaxation.

    PubMed

    Wohlmuth, Dominik; Epp, Viktor; Wilkening, Martin

    2015-08-24

    The development of safe and long-lasting all-solid-state batteries with high energy density requires a thorough characterization of ion dynamics in solid electrolytes. Commonly, conductivity spectroscopy is used to study ion transport; much less frequently, however, atomic-scale methods such as nuclear magnetic resonance (NMR) are employed. Here, we studied long-range as well as short-range Li ion dynamics in the glass-ceramic Li7 P3 S11 . Li(+) diffusivity was probed by using a combination of different NMR techniques; the results are compared with those obtained from electrical conductivity measurements. Our NMR relaxometry data clearly reveal a very high Li(+) diffusivity, which is reflected in a so-called diffusion-induced (6) Li NMR spin-lattice relaxation peak showing up at temperatures as low as 313 K. At this temperature, the mean residence time between two successful Li jumps is in the order of 3×10(8) s(-1) , which corresponds to a Li(+) ion conductivity in the order of 10(-4) to 10(-3) S cm(-1) . Such a value is in perfect agreement with expectations for the crystalline but metastable glass ceramic Li7 P3 S11 . In contrast to conductivity measurements, NMR analysis reveals a range of activation energies with values ranging from 0.17 to 0.26 eV, characterizing Li diffusivity in the bulk. In our case, through-going Li ion transport, when probed by using macroscopic conductivity spectroscopy, however, seems to be influenced by blocking grain boundaries including, for example, amorphous regions surrounding the Li7 P3 S11 crystallites. As a result of this, long-range ion transport as seen by impedance spectroscopy is governed by an activation energy of approximately 0.38 eV. The findings emphasize how surface and grain boundary effects can drastically affect long-range ionic conduction. If we are to succeed in solid-state battery technology, such effects have to be brought under control by, for example, sophisticated densification or through the preparation

  14. Time-resolved study of the extreme-ultraviolet emission and plasma dynamics of a sub-Joule, fast capillary discharge

    SciTech Connect

    Valenzuela, J. C.; Wyndham, E. S.; Favre, M.

    2015-08-15

    In this work, we discuss experimental observations on the dynamics of a fast, low energy capillary discharge when operated in argon and its properties as an intense source of extreme-ultraviolet (EUV) radiation. The discharge pre-ionization and self-triggering were accomplished by the use of the hollow cathode effect. This allowed a compact size and low inductance discharge with multi-kA current level and a quarter-period of ∼10 ns at sub-Joule energy level. We used the novel moiré and schlieren diagnostics with a 12 ps laser to obtain the time evolution of the line electron density and to study the plasma dynamics. EUV spectroscopy and filtered diodes were also implemented to estimate the plasma temperature and density throughout the evolution of the discharge. EUV source size was measured by using a filtered slit-wire camera. We observed that EUV emission starts from a compressed plasma on axis during the second quarter-period of the current and continues until the fifth quarter-period. Ionization levels from Ar VII to X were observed. By comparing the EUV emission spectra with synthetic spectra, we found that at the onset of emission (∼7 ns), the plasma is well fitted by a single Maxwellian electron distribution function with T{sub e} ∼ 12 eV and n{sub e} ∼ 10{sup 17 }cm{sup −3}. Close to peak emission (∼13 ns), plasma temperature and density increase to ∼20 eV and n{sub e} ∼ 10{sup 18 }cm{sup −3}, respectively. However, in order to successfully match the experimental data, a two component electron distribution function was necessary. Later in time, a smaller fraction in the high energy component and higher temperature suggests homogenization of the plasma. The moiré and schlieren diagnostics showed multiple radial compression-waves merging on axis throughout the discharge; they are an important heating mechanism that leads to a period of severe turbulence at peak EUV emission. It was also observed that emission

  15. Project FAST.

    ERIC Educational Resources Information Center

    Essexville-Hampton Public Schools, MI.

    Described are components of Project FAST (Functional Analysis Systems Training) a nationally validated project to provide more effective educational and support services to learning disordered children and their regular elementary classroom teachers. The program is seen to be based on a series of modules of delivery systems ranging from mainstream…

  16. Review: Intracardiac intracellular angiotensin system in diabetes

    PubMed Central

    Kumar, Rajesh; Yong, Qian Chen; Thomas, Candice M.

    2012-01-01

    The renin-angiotensin system (RAS) has mainly been categorized as a circulating and a local tissue RAS. A new component of the local system, known as the intracellular RAS, has recently been described. The intracellular RAS is defined as synthesis and action of ANG II intracellularly. This RAS appears to differ from the circulating and the local RAS, in terms of components and the mechanism of action. These differences may alter treatment strategies that target the RAS in several pathological conditions. Recent work from our laboratory has demonstrated significant upregulation of the cardiac, intracellular RAS in diabetes, which is associated with cardiac dysfunction. Here, we have reviewed evidence supporting an intracellular RAS in different cell types, ANG II's actions in cardiac cells, and its mechanism of action, focusing on the intracellular cardiac RAS in diabetes. We have discussed the significance of an intracellular RAS in cardiac pathophysiology and implications for potential therapies. PMID:22170614

  17. THE ALTERATION OF INTRACELLULAR ENZYMES

    PubMed Central

    Kaplan, J. Gordin

    1954-01-01

    1. The ability of homologous series of alcohols, ketones, and aldehydes to cause alteration of intracellular catalase increases approximately threefold for each methylene group added, thus following Traube's rule. Equiactive concentrations of alcohols (methanol to octanol) varied over a 4,000-fold range, yet the average corresponding surface tension was 42 ± 2 dynes/cm., that for ketones 43 ± 2, and for aldehydes (above C1) 41 ± 3. 2. Above C8 the altering activity of alcohols ceased to follow Traube's rule, and at C18 was nil. Yet the surface activities of alcohols from nonanol to dodecanol did follow Traube's rule. These two facts show that the interface which is being affected by these agents is not the cell surface, for if it were, altering activity should not fall off between C9 and C12 where surface activity is undiminished; they show also that micelle formation by short range association of hydrocarbon "tails," usually invoked to explain decrease in biological activity of compounds above C8, is not responsible for this effect in these experiments, in which permeability of the cell membrane probably is involved. 3. The most soluble alcohols and aldehydes (alcohols C1 to C8; aldehydes C1, C2), but not ketones, cause, above optimal concentration, an irreversible inhibition of yeast catalase. 4. The critical concentration of altering agent (i.e., that concentration just sufficient to cause doubling of the catalase activity of the yeast suspension) was independent of the concentration of the yeast cells. 5. Viability studies show that the number of yeast cells killed by the altering agents was not related to the degree of activation of the catalase produced. While all the cells were invariably killed by concentrations of altering agent which produced complete activation, all the cells had been killed by concentrations which were insufficient to cause more than 50 per cent maximal activation. Further, the evidence suggested that the catalase may be partially

  18. Separation of extra- and intracellular metabolites using hyperpolarized 13C diffusion weighted MR

    NASA Astrophysics Data System (ADS)

    Koelsch, Bertram L.; Sriram, Renuka; Keshari, Kayvan R.; Leon Swisher, Christine; Van Criekinge, Mark; Sukumar, Subramaniam; Vigneron, Daniel B.; Wang, Zhen J.; Larson, Peder E. Z.; Kurhanewicz, John

    2016-09-01

    This work demonstrates the separation of extra- and intracellular components of glycolytic metabolites with diffusion weighted hyperpolarized 13C magnetic resonance spectroscopy. Using b-values of up to 15,000 s mm-2, a multi-exponential signal response was measured for hyperpolarized [1-13C] pyruvate and lactate. By fitting the fast and slow asymptotes of these curves, their extra- and intracellular weighted diffusion coefficients were determined in cells perfused in a MR compatible bioreactor. In addition to measuring intracellular weighted diffusion, extra- and intracellular weighted hyperpolarized 13C metabolites pools are assessed in real-time, including their modulation with inhibition of monocarboxylate transporters. These studies demonstrate the ability to simultaneously assess membrane transport in addition to enzymatic activity with the use of diffusion weighted hyperpolarized 13C MR. This technique could be an indispensible tool to evaluate the impact of microenvironment on the presence, aggressiveness and metastatic potential of a variety of cancers.

  19. Investigation of plant control strategies for the supercritical C0{sub 2}Brayton cycle for a sodium-cooled fast reactor using the plant dynamics code.

    SciTech Connect

    Moisseytsev, A.; Sienicki, J.

    2011-04-12

    The development of a control strategy for the supercritical CO{sub 2} (S-CO{sub 2}) Brayton cycle has been extended to the investigation of alternate control strategies for a Sodium-Cooled Fast Reactor (SFR) nuclear power plant incorporating a S-CO{sub 2} Brayton cycle power converter. The SFR assumed is the 400 MWe (1000 MWt) ABR-1000 preconceptual design incorporating metallic fuel. Three alternative idealized schemes for controlling the reactor side of the plant in combination with the existing automatic control strategy for the S-CO{sub 2} Brayton cycle are explored using the ANL Plant Dynamics Code together with the SAS4A/SASSYS-1 Liquid Metal Reactor (LMR) Analysis Code System coupled together using the iterative coupling formulation previously developed and implemented into the Plant Dynamics Code. The first option assumes that the reactor side can be ideally controlled through movement of control rods and changing the speeds of both the primary and intermediate coolant system sodium pumps such that the intermediate sodium flow rate and inlet temperature to the sodium-to-CO{sub 2} heat exchanger (RHX) remain unvarying while the intermediate sodium outlet temperature changes as the load demand from the electric grid changes and the S-CO{sub 2} cycle conditions adjust according to the S-CO{sub 2} cycle control strategy. For this option, the reactor plant follows an assumed change in load demand from 100 to 0 % nominal at 5 % reduction per minute in a suitable fashion. The second option allows the reactor core power and primary and intermediate coolant system sodium pump flow rates to change autonomously in response to the strong reactivity feedbacks of the metallic fueled core and assumed constant pump torques representing unchanging output from the pump electric motors. The plant behavior to the assumed load demand reduction is surprising close to that calculated for the first option. The only negative result observed is a slight increase in the intermediate

  20. Miro1 Regulates Activity-Driven Positioning of Mitochondria within Astrocytic Processes Apposed to Synapses to Regulate Intracellular Calcium Signaling

    PubMed Central

    Stephen, Terri-Leigh; Higgs, Nathalie F.; Sheehan, David F.; Al Awabdh, Sana; López-Doménech, Guillermo; Arancibia-Carcamo, I. Lorena

    2015-01-01

    It is fast emerging that maintaining mitochondrial function is important for regulating astrocyte function, although the specific mechanisms that govern astrocyte mitochondrial trafficking and positioning remain poorly understood. The mitochondrial Rho-GTPase 1 protein (Miro1) regulates mitochondrial trafficking and detachment from the microtubule transport network to control activity-dependent mitochondrial positioning in neurons. However, whether Miro proteins are important for regulating signaling-dependent mitochondrial dynamics in astrocytic processes remains unclear. Using live-cell confocal microscopy of rat organotypic hippocampal slices, we find that enhancing neuronal activity induces transient mitochondrial remodeling in astrocytes, with a concomitant, transient reduction in mitochondrial trafficking, mediated by elevations in intracellular Ca2+. Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the Ca2+-sensing EF-hand domains of Miro1 are important for regulating mitochondrial trafficking in astrocytes and required for activity-driven mitochondrial confinement near synapses. Additionally, activity-dependent mitochondrial positioning by Miro1 reciprocally regulates the levels of intracellular Ca2+ in astrocytic processes. Thus, the regulation of intracellular Ca2+ signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte Ca2+ wave propagation, gliotransmission, and ultimately neuronal function. SIGNIFICANCE STATEMENT Mitochondria are key cellular organelles that play important roles in providing cellular energy and buffering intracellular calcium ions. The mechanisms that control mitochondrial distribution within the processes of glial cells called astrocytes and the impact this may have on calcium signaling remains unclear. We show that activation of glutamate receptors or increased neuronal

  1. On the Computing Potential of Intracellular Vesicles

    PubMed Central

    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. PMID:26431435

  2. On the Computing Potential of Intracellular Vesicles.

    PubMed

    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.

  3. Intracellular Organisms as Placental Invaders

    PubMed Central

    Vigliani, Marguerite B.; Bakardjiev, Anna I.

    2015-01-01

    In this article we present a novel model for how the human placenta might get infected via the hematogenous route. We present a list of diverse placental pathogens, like Listeria monocytogenes or Cytomegalovirus, which are familiar to most obstetricians, but others, like Salmonella typhi, have only been reported in case studies or small case series. Remarkably, all of these organisms on this list are either obligate or facultative intracellular organisms. These pathogens are able to enter and survive inside host immune cells for at least a portion of their life cycle. We suggest that many blood-borne pathogens might arrive at the placenta via transportation inside of maternal leukocytes that enter the decidua in early pregnancy. We discuss mechanisms by which extravillous trophoblasts could get infected in the decidua and spread infection to other layers in the placenta. We hope to raise awareness among OB/GYN clinicians that organisms not typically associated with the TORCH list might cause placental infections and pregnancy complications. PMID:27695204

  4. Secretome of obligate intracellular Rickettsia

    PubMed Central

    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

  5. Twenty years of fluorescence imaging of intracellular chloride

    PubMed Central

    Arosio, Daniele; Ratto, Gian Michele

    2014-01-01

    Chloride homeostasis has a pivotal role in controlling neuronal excitability in the adult brain and during development. The intracellular concentration of chloride is regulated by the dynamic equilibrium between passive fluxes through membrane conductances and the active transport mediated by importers and exporters. In cortical neurons, chloride fluxes are coupled to network activity by the opening of the ionotropic GABAA receptors that provides a direct link between the activity of interneurons and chloride fluxes. These molecular mechanisms are not evenly distributed and regulated over the neuron surface and this fact can lead to a compartmentalized control of the intracellular concentration of chloride. The inhibitory drive provided by the activity of the GABAA receptors depends on the direction and strength of the associated currents, which are ultimately dictated by the gradient of chloride, the main charge carrier flowing through the GABAA channel. Thus, the intracellular distribution of chloride determines the local strength of ionotropic inhibition and influences the interaction between converging excitation and inhibition. The importance of chloride regulation is also underlined by its involvement in several brain pathologies, including epilepsy and disorders of the autistic spectra. The full comprehension of the physiological meaning of GABAergic activity on neurons requires the measurement of the spatiotemporal dynamics of chloride fluxes across the membrane. Nowadays, there are several available tools for the task, and both synthetic and genetically encoded indicators have been successfully used for chloride imaging. Here, we will review the available sensors analyzing their properties and outlining desirable future developments. PMID:25221475

  6. Hydrophilic fluorescent nanogel thermometer for intracellular thermometry.

    PubMed

    Gota, Chie; Okabe, Kohki; Funatsu, Takashi; Harada, Yoshie; Uchiyama, Seiichi

    2009-03-04

    The first methodology to measure intracellular temperature is described. A highly hydrophilic fluorescent nanogel thermometer developed for this purpose stays in the cytoplasm and emits stronger fluorescence at a higher temperature. Thus, intracellular temperature variations associated with biological processes can be monitored by this novel thermometer with a temperature resolution of better than 0.5 degrees C.

  7. Single-cell intracellular nano-pH probes.

    PubMed

    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.

  8. Disruption of intracellular calcium regulation is integral to aminoglycoside-induced hair cell death.

    PubMed

    Esterberg, Robert; Hailey, Dale W; Coffin, Allison B; Raible, David W; Rubel, Edwin W

    2013-04-24

    Intracellular Ca(2+) is a key regulator of life or death decisions in cultured neurons and sensory cells. The role of Ca(2+) in these processes is less clear in vivo, as the location of these cells often impedes visualization of intracellular Ca(2+) dynamics. We generated transgenic zebrafish lines that express the genetically encoded Ca(2+) indicator GCaMP in mechanosensory hair cells of the lateral line. These lines allow us to monitor intracellular Ca(2+) dynamics in real time during aminoglycoside-induced hair cell death. After exposure of live larvae to aminoglycosides, dying hair cells undergo a transient increase in intracellular Ca(2+) that occurs shortly after mitochondrial membrane potential collapse. Inhibition of intracellular Ca(2+) elevation through either caged chelators or pharmacological inhibitors of Ca(2+) effectors mitigates toxic effects of aminoglycoside exposure. Conversely, artificial elevation of intracellular Ca(2+) by caged Ca(2+) release agents sensitizes hair cells to the toxic effects of aminoglycosides. These data suggest that alterations in intracellular Ca(2+) homeostasis play an essential role in aminoglycoside-induced hair cell death, and indicate several potential therapeutic targets to stem ototoxicity.

  9. Intracellular Calcium Gradients in Single Living Cells: Measurement and Analysis by Optical and Digital Techniques

    NASA Astrophysics Data System (ADS)

    Yelamarty, Rao Viswanadha

    Intracellular calcium (Ca^{2+ }) has been considered as a regulator of many cellular processes. In addition, Ca^{2+ } also plays a key role in mediating actions of many hormones, growth factors, and drugs. This thesis describes two general approaches, digital video and photomultiplier (PMT) based fluorescence microscopic systems, to measure such Ca^{2+} changes throughout the cell. They reveal the heterogeneous spatial and fast temporal changes of Ca^{2+} within a single isolated living cell. In order to measure spatial Ca^ {2+} in three dimensions (3-D), optical section microscopy (OSM) coupled to digital video imaging is introduced. With this approach, an increase in nuclear Ca^{2+} compared to cytosolic Ca^{2+} is detected in human erythroblasts and rat hepatocytes under the addition of growth factors: erythropoietin and epidermal growth factor respectively. In addition, the primary effect of non growth-promoting hormone vasopressin, raise in cytosolic Ca^{2+}, is also observed. These observations are the first to underscore the importance of nuclear Ca^{2+} increase in cell growth and differentiation. On the other hand, to track fast Ca^ {2+} transients (mesc) during excitation -contraction (EC) cycle and then examine alterations in Ca^{2+} transients in healthy and diseased (hypertensive) heart cells, a PMT based system is implemented. Significant alterations in Ca^{2+} transients in hypertensive heart cells were observed. This finding is compatible with the clinical finding that patients with hypertensive cardiomyopathy suffer a lack of adequate relaxation. Finally, to correlate the Ca^{2+} dynamics in an EC cycle with mechanical activity, a hybrid optical digital processor was developed. The performance of the hybrid processor is analyzed and applied simultaneously with the PMT based system. The mechanical contraction and relaxation of a single cardiac cell closely paralleled that of Ca^{2+} dynamics during an EC cycle. In summary, this thesis illustrates

  10. Membranes, mechanics, and intracellular transport

    NASA Astrophysics Data System (ADS)

    Parthasarathy, Raghuveer

    2012-10-01

    Cellular membranes are remarkable materials -- self-assembled, flexible, two-dimensional fluids. Understanding how proteins manipulate membrane curvature is crucial to understanding the transport of cargo in cells, yet the mechanical activities of trafficking proteins remain poorly understood. Using an optical-trap based assay involving dynamic deformation of biomimetic membranes, we have examined the behavior of Sar1, a key component of the COPII family of transport proteins. We find that Sar1 from yeast (S. cerevisiae) lowers membrane rigidity by up to 100% as a function of its concentration, thereby lowering the energetic cost of membrane deformation. Human Sar1 proteins can also lower the mechanical rigidity of the membranes to which they bind. However, unlike the yeast proteins, the rigidity is not a monotonically decreasing function of concentration but rather shows increased rigidity and decreased mobility at high concentrations that implies interactions between proteins. In addition to describing this study of membrane mechanics, I'll also discuss some topics relevant to a range of biophysical investigations, such as the insights provided by imaging methods and open questions in the dynamics of multicellular systems.

  11. Optical Torques on Upconverting Particles for Intracellular Microrheometry.

    PubMed

    Rodríguez-Sevilla, Paloma; Zhang, Yuhai; de Sousa, Nuno; Marqués, Manuel I; Sanz-Rodríguez, Francisco; Jaque, Daniel; Liu, Xiaogang; Haro-González, Patricia

    2016-12-14

    Precise knowledge and control over the orientation of individual upconverting particles is extremely important for full exploiting their capabilities as multifunctional bioprobes for interdisciplinary applications. In this work, we report on how time-resolved, single particle polarized spectroscopy can be used to determine the orientation dynamics of a single upconverting particle when entering into an optical trap. Experimental results have unequivocally evidenced the existence of a unique stable configuration. Numerical simulations and simple numerical calculations have demonstrated that the dipole magnetic interactions between the upconverting particle and trapping radiation are the main mechanisms responsible of the optical torques that drive the upconverting particle to its stable orientation. Finally, how a proper analysis of the rotation dynamics of a single upconverting particle within an optical trap can provide valuable information about the properties of the medium in which it is suspended is demonstrated. A proof of concept is given in which the laser driven intracellular rotation of upconverting particles is used to successfully determine the intracellular dynamic viscosity by a passive and an active method.

  12. Intracellular minerals and metal deposits in prokaryotes.

    PubMed

    Edwards, K J; Bazylinski, D A

    2008-06-01

    Thanks to the work of Terrance J. Beveridge and other pioneers in the field of metal-microbe interactions, prokaryotes are well known to sequester metals and other ions intracellularly in various forms. These forms range from poorly ordered deposits of metals to well-ordered mineral crystals. Studies on well-ordered crystalline structures have generally focused on intracellular organelles produced by magnetotactic bacteria that are ubiquitous in terrestrial and marine environments that precipitate Fe(3)O(4) or Fe(3)S(4), Fe-bearing minerals that have magnetic properties and are enclosed in intracellular membranes. In contrast, studies on less-well ordered minerals have focused on Fe-, As-, Mn-, Au-, Se- and Cd-precipitates that occur intracellularly. The biological and environmental function of these particles remains a matter of debate.

  13. Nanoparticles for intracellular-targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Paulo, Cristiana S. O.; Pires das Neves, Ricardo; Ferreira, Lino S.

    2011-12-01

    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.

  14. Modulation of lipoprotein receptor functions by intracellular adaptor proteins.

    PubMed

    Stolt, Peggy C; Bock, Hans H

    2006-10-01

    Members of the low density lipoprotein (LDL) receptor gene family are critically involved in a wide range of physiological processes including lipid and vitamin homeostasis, cellular migration, neurodevelopment, and synaptic plasticity, to name a few. Lipoprotein receptors exert these diverse biological functions by acting as cellular uptake receptors or by inducing intracellular signaling cascades. It was discovered that a short sequence in the intracellular region of all lipoprotein receptors, Asn-Pro-X-Tyr (NPXY) is important for mediating either endocytosis or signal transduction events, and that this motif serves as a binding site for phosphotyrosine-binding (PTB) domain containing scaffold proteins. These molecular adaptors connect the transmembrane receptors with the endocytosis machinery and regulate cellular trafficking, or function as assembly sites for dynamic multi-protein signaling complexes. Whereas the LDL receptor represents the archetype of an endocytic lipoprotein receptor, the structurally closely related apolipoprotein E receptor 2 (apoER2) and very low density lipoprotein (VLDL) receptor activate a kinase-dependent intracellular signaling cascade after binding to the neuronal signaling molecule Reelin. This review focuses on two related PTB domain containing adaptor proteins that mediate these divergent lipoprotein receptor responses, ARH (autosomal recessive hypercholesterolemia protein) and Dab1 (disabled-1), and discusses the structural and molecular basis of this different behaviour.

  15. Potent Antibacterial Nanoparticles against Biofilm and Intracellular Bacteria

    NASA Astrophysics Data System (ADS)

    Mu, Haibo; Tang, Jiangjiang; Liu, Qianjin; Sun, Chunli; Wang, Tingting; Duan, Jinyou

    2016-01-01

    The chronic infections related to biofilm and intracellular bacteria are always hard to be cured because of their inherent resistance to both antimicrobial agents and host defenses. Herein we develop a facile approach to overcome the above conundrum through phosphatidylcholine-decorated Au nanoparticles loaded with gentamicin (GPA NPs). The nanoparticles were characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS) and ultraviolet‑visible (UV‑vis) absorption spectra which demonstrated that GPA NPs with a diameter of approximately 180 nm were uniform. The loading manner and release behaviors were also investigated. The generated GPA NPs maintained their antibiotic activities against planktonic bacteria, but more effective to damage established biofilms and inhibited biofilm formation of pathogens including Gram-positive and Gram-negative bacteria. In addition, GPA NPs were observed to be nontoxic to RAW 264.7 cells and readily engulfed by the macrophages, which facilitated the killing of intracellular bacteria in infected macrophages. These results suggested GPA NPs might be a promising antibacterial agent for effective treatment of chronic infections due to microbial biofilm and intracellular bacteria.

  16. Intracellular Protein Delivery for Treating Breast Cancer

    DTIC Science & Technology

    2014-08-01

    nanocapsules with specific cancer cell targeting ligands; Task 3. Preparing and testing of MMP activatable cell penetrating peptides (ACCPs)-coupled...AD_________________ Award Number: W81XWH-11-1-0371 TITLE: Intracellular Protein Delivery for Treating Breast Cancer PRINCIPAL INVESTIGATOR: Dr...SUBTITLE Intracellular Protein Delivery for Treating Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0371 5c. PROGRAM ELEMENT NUMBER 6

  17. Optical PEBBLE nanosensors and fiber optic sensors for real-time intracellular imaging and analysis of magnesium and oxygen

    NASA Astrophysics Data System (ADS)

    Park, Edwin J.

    A highly selective magnesium fluorescent optical nanosensor, made possible by PEBBLE (Probe Encapsulated By Biologically Localized Embedding) technology is presented. Ratiometric sensors were prepared, via a microemulsion polymerization process, by co-immobilizing a highly selective magnesium dye with a reference dye inside a polymer matrix. The resultant spherical sensors are ˜40 nm in diameter. Several dyes were investigated with coumarin 343 (C343) providing the best selectivity towards Mg2+ vs. ions such as Ca 2+, Na+, and K+. The dynamic range of the sensors was 1 to 30 mM (linear from 1 to 10 mM) with a response time of less than 4 s. The fully reversible sensors exhibit minimal leaching and photobleaching. In vitro intracellular changes in Mg2+ concentration were monitored in C6 Glioma cells. Preliminary experiments demonstrated the capability of these sensors thus they were used to investigate the PhoP/Q transmembrane protein system on the internal membrane of salmonella . The sensors were used to monitor the magnesium levels inside salmonella containing vacuoles. Previously believed hypotheses on changes in magnesium concentration are challenged with the newly obtained results. The selectivity for Mg2+ along with the biocompatibility of the matrix of these sensors provides a new and reliable tool for intracellular magnesium measurements. A second sensor platform was developed for the detection of intracellular dissolved oxygen, using a fiber optic probe. The design and fabrication of an oxygen fiber optic sensor based on the fluorescence quenching properties of the oxygen sensitive platinum (II) octaethylporphine ketone (PtOEPK) is presented. Octaethyl porphyrin (OEP) or bodipy maleimide 577/618, was also entrapped, as a reference dye, in a polyvinyl chloride matrix including the plasticizing agent bis 2-ethylhexyl sebacate (DOS). The multi mode fibers were pulled down to submicron dimensions and a dip coating procedure was used to apply the sensing

  18. Umami changes intracellular Ca2+ levels using intracellular and extracellular sources in mouse taste receptor cells.

    PubMed

    Narukawa, Masataka; Mori, Tomohiko; Hayashi, Yukako

    2006-11-01

    Recently, candidates for umami receptors have been identified in taste cells, but the precise transduction mechanisms of the downstream receptor remain unknown. To investigate how intracellular Ca(2+) increases in the umami transduction pathway, we measured changes in intracellular Ca(2+) levels in response to umami stimuli monosodium glutamate (MSG), IMP, and MSG + IMP in mouse taste receptor cells (TRCs) by Ca(2+) imaging. Even when extracellular Ca(2+) was absent, 1/3 of umami-responsive TRCs exhibited increased intracellular Ca(2+) levels. When intracellular Ca(2+) was depleted, half of the TRCs retained their response to umami. These results suggest that umami-responsive TRCs increase their intracellular Ca(2+) levels through two pathways: by releasing Ca(2+) from intracellular stores and by an influx of Ca(2+) from extracellular sources. We conclude that the Ca(2+) influx from extracellular source might play an important role in the synergistic effect between MSG and IMP.

  19. Dual Readout BRET/FRET Sensors for Measuring Intracellular Zinc

    PubMed Central

    2016-01-01

    Genetically encoded FRET-based sensor proteins have significantly contributed to our current understanding of the intracellular functions of Zn2+. However, the external excitation required for these fluorescent sensors can give rise to photobleaching and phototoxicity during long-term imaging, limits applications that suffer from autofluorescence and light scattering, and is not compatible with light-sensitive cells. For these applications, sensor proteins based on Bioluminescence Resonance Energy Transfer (BRET) would provide an attractive alternative. In this work, we used the bright and stable luciferase NanoLuc to create the first genetically encoded BRET sensors for measuring intracellular Zn2+. Using a new sensor approach, the NanoLuc domain was fused to the Cerulean donor domain of two previously developed FRET sensors, eCALWY and eZinCh-2. In addition to preserving the excellent Zn2+ affinity and specificity of their predecessors, these newly developed sensors enable both BRET- and FRET-based detection. While the dynamic range of the BRET signal for the eCALWY-based BLCALWY-1 sensor was limited by the presence of two competing BRET pathways, BRET/FRET sensors based on the eZinCh-2 scaffold (BLZinCh-1 and -2) yielded robust 25–30% changes in BRET ratio. In addition, introduction of a chromophore-silencing mutation resulted in a BRET-only sensor (BLZinCh-3) with increased BRET response (50%) and an unexpected 10-fold increase in Zn2+ affinity. The combination of robust ratiometric response, physiologically relevant Zn2+ affinities, and stable and bright luminescence signal offered by the BLZinCh sensors allowed monitoring of intracellular Zn2+ in plate-based assays as well as intracellular BRET-based imaging in single living cells in real time. PMID:27547982

  20. Systematic investigation on the intracellular trafficking network of polymeric nanoparticles.

    PubMed

    Zhang, Jinxie; Chang, Danfeng; Yang, Yao; Zhang, Xudong; Tao, Wei; Jiang, Lijuan; Liang, Xin; Tsai, Hsiangi; Huang, Laiqiang; Mei, Lin

    2017-02-22

    Polymeric nanoparticles such as PLGA-based nanoparticles are emerging as promising carriers for controlled drug delivery. However, little is known about the intracellular trafficking network of polymeric nanoparticles. Here, more than 30 Rab proteins were used as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy to investigate in detail the intracellular trafficking pathways of PLGA nanoparticles. We observed that coumarin-6-loaded PLGA nanoparticles were internalized by the cells mainly through caveolin and clathrin-dependent endocytosis and Rab34-mediated macropinocytosis. Then the PLGA nanoparticles were transported to early endosomes (EEs), late endosomes (LEs), and finally to lysosomes. Two novel transport pathways were identified in our research: the macropinocytosis (Rab34 positive)-LE (Rab7 positive)-lysosome pathway and the EE-liposome (Rab18)-lysosome pathway. Moreover, the slow (Rab11 and Rab35 positive), fast (Rab4 positive) and apical (Rab20 and Rab25 positive) endocytic recycling endosome pathways could transport the PLGA nanoparticles to lysosomes. The PLGA nanoparticles were transported out of the cells by GLUT4 transport vesicles (Rab8, Rab10 positive), classic secretory vesicles (Rab3, Rab27 positive vesicles) and melanosomes (Rab32, Rab38 positive vesicles). Besides, the PLGA nanoparticles were observed in autophagosomes (LC3 positive), which means that the nanoparticles can be delivered by the autophagy pathway. Multiple cross-talk pathways were identified connecting autophagy and endocytosis or exocytosis by screening the co-localization of the Rab proteins with the LC3 protein. Degradation of nanoparticles through lysosomes can be blocked by autophagy inhibitors (3 MA and CQ). A better understanding of intracellular trafficking mechanisms involved in polymeric nanoparticle-based drug delivery is a prerequisite to clinical application.

  1. Antibody-antigen kinetics constrain intracellular humoral immunity

    PubMed Central

    Bottermann, Maria; Lode, Heidrun Elisabeth; Watkinson, Ruth E.; Foss, Stian; Sandlie, Inger; Andersen, Jan Terje; James, Leo C.

    2016-01-01

    During infection with non-enveloped viruses, antibodies stimulate immunity from inside cells by activating the cytosolic Fc receptor TRIM21. This intracellular humoral response relies on opsonized viral particles reaching the cytosol intact but the antigenic and kinetic constraints involved are unknown. We have solved the structure of a potent TRIM21-dependent neutralizing antibody in complex with human adenovirus 5 hexon and show how these properties influence immune activity. Structure-guided mutagenesis was used to generate antibodies with 20,000-fold variation in affinity, on-rates that differ by ~50-fold and off-rates by >175-fold. Characterization of these variants during infection revealed that TRIM21-dependent neutralization and NFκB activation was largely unaffected by on-rate kinetics. In contrast, TRIM21 antiviral activity was exquisitely dependent upon off-rate, with sub-μM affinity antibodies nevertheless unable to stimulate signaling because of fast dissociation kinetics. These results define the antibody properties required to elicit an efficient intracellular immune response during viral infection. PMID:27881870

  2. Insider trading: Extracellular matrix proteins and their non-canonical intracellular roles.

    PubMed

    Hellewell, Andrew L; Adams, Josephine C

    2016-01-01

    In metazoans, the extracellular matrix (ECM) provides a dynamic, heterogeneous microenvironment that has important supportive and instructive roles. Although the primary site of action of ECM proteins is extracellular, evidence is emerging for non-canonical intracellular roles. Examples include osteopontin, thrombospondins, IGF-binding protein 3 and biglycan, and relate to roles in transcription, cell-stress responses, autophagy and cancer. These findings pose conceptual problems on how proteins signalled for secretion can be routed to the cytosol or nucleus, or can function in environments with diverse redox, pH and ionic conditions. We review evidence for intracellular locations and functions of ECM proteins, and current knowledge of the mechanisms by which they may enter intracellular compartments. We evaluate the experimental methods that are appropriate to obtain rigorous evidence for intracellular localisation and function. Better insight into this under-researched topic is needed to decipher the complete spectrum of physiological and pathological roles of ECM proteins.

  3. Hybrid simulation of fast ion dynamics in the presence of off-axis fishbone-like modes in high-beta JT-60U plasmas

    NASA Astrophysics Data System (ADS)

    Bierwage, Andreas; Aiba, Nobuyuki; Matsunaga, Go; Shinohara, Koji; Todo, Yasushi; Yagi, Masatoshi

    2013-10-01

    The MHD-PIC hybrid code MEGA is used to simulate high-beta JT-60U plasmas in regimes near marginal MHD ballooning stability and driven by neutral beams. The goal of this research is to study the transport of fast ions caused by experimentally observed fishbone-like modes that peak off-axis (near the q = 2 surface) and have frequencies well below the accumulation points of the beta-induced gap of the shear Alfvén continuum. The approach chosen is as follows. Before examining the physics via parameter scans and case studies, the relevance of the simulation model is verified by checking whether the code can reproduce a plasma response with properties similar to those seen in the experiments. For this purpose, the simulation scenario is set up as realistically as currently possible: with realistic plasma shape and bulk pressure, and a fast ion distribution that is consistent with particle sources and collisions. The methods used and first results are reported and discussed. This work is partly supported by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS).

  4. Local intracellular ion measurements with luminescent indicators using confocal laser scanning microscopy

    NASA Astrophysics Data System (ADS)

    Opitz, N.; Merten, E.; Acker, H.

    1995-09-01

    Ion sensitive fluoroprobes such as BCECF (pH) and FURA-II (Ca2+) are frequently used indicators for determination of ion activities in single cells and subcellular compartments, e.g. by video enhanced or video intensified microscopy. Moreover, using confocal laser scanning microscopy (CLSM) with its inherent potential for noninvasive optical sectioning of cells and tissues and subsequent 3D image reconstruction, intracellular ion topographies can be monitored via pseudocolor encoded ratio imaging from pixel to pixel enabling in vivo measurements of dynamic intracellular processes. Regardless of the degree of spatial resolution, reliable qualtitative determinations essentially depend on accurate calibration of the intracellularly entrapped fluoroprobe. Calibration is either established on the basis of a whole cell or within a more or less extended subcellular compartment and the characteristics are displayed as concentration encoded pseudocolor bar within the image frame. This calibration is assumed to be valid for other cellular compartments and, in case of ion imaging, it is even thought to be valid for every single pixel of the complete pixel field. However, the assumption of a topographically invariant intracellular calibration requires a reliable behavior of the intracellularly applied indicator. This intracellular integrity of the dyes often does not seem to exist since intracellular calibration curves considerably deviate from in vitro calibration characteristics. Deviations may be due to intracellular interactions of indicator molecules with cytoplasmic macromolecules, e.g. proteins, resulting in spectral distortions and/or sensitivity deficits as demonstrated by the indicators BCECF and FURA-RED (a FURA-II analogue) or to intracellular redistribution of the indicator as exemplified by pH measurements using carboxy-SNARF-1. Consequences of these investigations as well as further potential interferences are discussed with special respect to ion imaging

  5. Targeted intracellular delivery of therapeutics: an overview.

    PubMed

    Rawat, A; Vaidya, B; Khatri, K; Goyal, A K; Gupta, P N; Mahor, S; Paliwal, R; Rai, S; Vyas, S P

    2007-09-01

    During the last decade, intracellular drug delivery has become an emerging area of research in the medical and pharmaceutical field. Many therapeutic agents such as drugs and DNA/oligonucleotides can be delivered not just to the cell but also to a particular compartment of that cell to achieve better activity e.g. proapoptotic drugs to the mitochondria, antibiotics and enzymes to the lysosomes and various anticancer drugs and gene to the nucleus. The lipidic nature of biological membrans is the major obstacle to the intracellular delivery of macromolecular and ionic drugs. Additionally, after endocytosis, the lysosome, the major degradation compartment, needs to be avoided for better activity. To avoid these problems, various carriers have been investigated for efficient intracellular delivery, either by direct entry to cytoplasm or by escaping the endosomal compartment. These include cell penetrating peptides, and carrier systems such as liposomes, cationic lipids and polymers, polymeric nanoparticles, etc. Various properties of these carriers, including size, surface charge, composition and the presence of cell specific ligands, alter their efficacy and specificity towards particular cells. This review summarizes various aspects of targeted intracellular delivery of therapeutics including pathways, mechanisms and approaches. Various carrier constructs having potential for targeted intracellular delivery are also been discussed.

  6. Internal affairs: investigating the Brucella intracellular lifestyle.

    PubMed

    von Bargen, Kristine; Gorvel, Jean-Pierre; Salcedo, Suzana P

    2012-05-01

    Bacteria of the genus Brucella are Gram-negative pathogens of several animal species that cause a zoonotic disease in humans known as brucellosis or Malta fever. Within their hosts, brucellae reside within different cell types where they establish a replicative niche and remain protected from the immune response. The aim of this article is to discuss recent advances in the field in the specific context of the Brucella intracellular 'lifestyle'. We initially discuss the different host cell targets and their relevance during infection. As it represents the key to intracellular replication, the focus is then set on the maturation of the Brucella phagosome, with particular emphasis on the Brucella factors that are directly implicated in intracellular trafficking and modulation of host cell signalling pathways. Recent data on the role of the type IV secretion system are discussed, novel effector molecules identified and how some of them impact on trafficking events. Current knowledge on Brucella gene regulation and control of host cell death are summarized, as they directly affect intracellular persistence. Understanding how Brucella molecules interplay with their host cell targets to modulate cellular functions and establish the intracellular niche will help unravel how this pathogen causes disease.

  7. Efficient intracellular delivery and improved biocompatibility of colloidal silver nanoparticles towards intracellular SERS immuno-sensing.

    PubMed

    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.

  8. Characterization of Intracellular Streaming and Traction Forces in Migrating Physarum Plasmodia

    NASA Astrophysics Data System (ADS)

    Zhang, Shun; Meili, Ruedi; Guy, Robert D.; Lasheras, Juan C.; Del Alamo, Juan C.

    2013-11-01

    Physarum plasmodium is a model organism for cell migration that exhibits fast intracellular streaming. Single amoebae were seeded and allowed to move on polyacrilamide gels that contained 0.2 μm fluorescent beads. Joint time-lapse sequences of intracellular streaming and gel deformation were acquired respectively in the bright and fluorescent fields of a confocal microscope. Images were analyzed using particle image velocimetry (PIV) algorithms, and the traction stresses applied by the amoebae on the surface were computed by solving the elastostatic equation for the gel. These measurements provide, for the first time, a joint characterization of intracellular mass transport and the forces applied on the substrate of motile amoeboid cells with high resolution in both time and space, enables a through study about the locomotive mechanism and the relation between intracellular flow and traction stress, shedding light on related biomimetic research. The results reveal a pronounced auto-oscillation character in intracellular flow, contact area, centroid speed and strain energy, all with the same periodicity about 60 seconds. Adhesion sites are found to be almost stationary while a traction wave propagates from the tail to the anterior region in each cycle.

  9. Characterization of Intracellular Streaming and Traction Forces in Migrating Physarum Plasmodia

    NASA Astrophysics Data System (ADS)

    Zhang, Shun; Meili, Ruedi; Guy, Robert; Lasheras, Juan; Del Alamo, Juan C.

    2014-11-01

    Physarum plasmodium is a model organism for cell migration that exhibits fast intracellular streaming. Single amoebae were seeded and allowed to move on polyacrilamide gels that contained 0.5-micron fluorescent beads. Joint time-lapse sequences of intracellular streaming and gel deformation were acquired respectively in the bright and fluorescent fields under microscope. These images were analyzed using particle image velocimetry (PIV) algorithms, and the traction stresses applied by the amoebae on the surface were computed by solving the elastostatic equation for the gel using the measured bead displacements as boundary conditions. These measurements provide, for the first time, a joint characterization of intracellular mass transport and the forces applied on the substrate of motile amoeboid cells with high resolution in both time and space, enables a through study about the locomotive mechanism and the relation between intracellular flow and traction stress, shedding light on related biomimetic research. The results reveal a pronounced auto-oscillation character in intracellular flow, contact area, centroid speed and strain energy, all with the same periodicity about 100 seconds. Locomotion modes that were distinct in flow/ traction stress pattern as well as migration speed have been discovered and studied.

  10. Single-cell RNA-seq ties macrophage polarization to growth rate of intracellular Salmonella.

    PubMed

    Saliba, Antoine-Emmanuel; Li, Lei; Westermann, Alexander J; Appenzeller, Silke; Stapels, Daphne A C; Schulte, Leon N; Helaine, Sophie; Vogel, Jörg

    2016-11-14

    Intracellular bacterial pathogens can exhibit large heterogeneity in growth rate inside host cells, with major consequences for the infection outcome. If and how the host responds to this heterogeneity remains poorly understood. Here, we combined a fluorescent reporter of bacterial cell division with single-cell RNA-sequencing analysis to study the macrophage response to different intracellular states of the model pathogen Salmonella enterica serovar Typhimurium. The transcriptomes of individual infected macrophages revealed a spectrum of functional host response states to growing and non-growing bacteria. Intriguingly, macrophages harbouring non-growing Salmonella display hallmarks of the proinflammatory M1 polarization state and differ little from bystander cells, suggesting that non-growing bacteria evade recognition by intracellular immune receptors. By contrast, macrophages containing growing bacteria have turned into an anti-inflammatory, M2-like state, as if fast-growing intracellular Salmonella overcome host defence by reprogramming macrophage polarization. Additionally, our clustering approach reveals intermediate host functional states between these extremes. Altogether, our data suggest that gene expression variability in infected host cells shapes different cellular environments, some of which may favour a growth arrest of Salmonella facilitating immune evasion and the establishment of a long-term niche, while others allow Salmonella to escape intracellular antimicrobial activity and proliferate.

  11. Characterization of Intracellular Streaming and Traction Forces in Migrating Physarum Plasmodia

    NASA Astrophysics Data System (ADS)

    Zhang, Shun; Lewis, Owen; Guy, Robert; Del Alamo, Juan Carlos

    2015-11-01

    Physarum plasmodium is a model organism for cell migration that exhibits fast intracellular streaming. Single amoebae were seeded and allowed to move on polyacrilamide gels that contained 0.5-micron fluorescent beads. Joint time-lapse sequences of intracellular streaming and gel deformation were acquired respectively in the bright and fluorescent fields under microscope. These images were analyzed using particle image velocimetry (PIV) algorithms, and the traction stresses applied by the amoebae on the surface were computed by solving the elastostatic equation for the gel using the measured bead displacements as boundary conditions. These measurements provide, for the first time, a joint characterization of intracellular mass transport, the forces applied on the substrate and the signal of free intracellular calcium with high resolution in both time and space, enables a through study about the locomotive mechanism, shedding light on related biomimetic research. The results reveal a pronounced auto-oscillation character in intracellular flow, contact area, centroid speed and strain energy, all with the same periodicity about 100 seconds. Locomotion modes that were distinct in flow/ traction stress pattern as well as migration speed have been discovered and studied.

  12. Macrophage defense mechanisms against intracellular bacteria.

    PubMed

    Weiss, Günter; Schaible, Ulrich E

    2015-03-01

    Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics.

  13. Evaluation of two dynamic in vitro models simulating fasted and fed state conditions in the upper gastrointestinal tract (TIM-1 and tiny-TIM) for investigating the bioaccessibility of pharmaceutical compounds from oral dosage forms.

    PubMed

    Verwei, Miriam; Minekus, Mans; Zeijdner, Evelijn; Schilderink, Ronald; Havenaar, Robert

    2016-02-10

    Pharmaceutical research needs predictive in vitro tools for API bioavailability in humans. We evaluated two dynamic in vitro gastrointestinal models: TIM-1 and tiny-TIM. Four low-soluble APIs in various formulations were investigated in the TIM systems under fasted and fed conditions. API small-intestinal bioaccessibility profiles were evaluated between the two systems and in comparison with human data. Both TIM systems showed a higher bioaccessibility of ciprofloxacin and nifedipine during 3-4h after dosing immediate release (IR) compared to modified release (MR) formulations. Higher bioaccessibility levels from IR formulations were observed under fasted state in the first 30-90 min in tiny-TIM as compared to TIM-1, resulting in a tmax similar to clinical data. Absence (ciprofloxacin) or presence (posaconazole) of a food effect on bioaccessibility was observed in both TIM systems in line with human data. A higher bioaccessibility of fenofibrate from nano- vs micro-particle formulation was found in both TIM systems. This dataset shows the predictive quality of the TIM systems for clinical data on API small-intestinal bioaccessibility from IR and MR formulations and food effects. Tiny-TIM provides higher throughput and better prediction for IR formulations. TIM-1 provides detailed information on site-specific release of APIs, relevant for MR formulations and food effects.

  14. NMR measurements of intracellular ions in hypertension

    NASA Astrophysics Data System (ADS)

    Veniero, Joseph C.; Gupta, R. K.

    1993-08-01

    The NMR methods for the measurement of intracellular free Na+, K+, Mg2+, Ca2+, and H+ are introduced. The recent literature is then presented showing applications of these methods to cells and tissues from hypertensive animal model systems, and humans with essential hypertension. The results support the hypothesis of consistent derangement of the intracellular ionic environment in hypertension. The theory that this derangement may be a common link in the disease states of high blood pressure and abnormal insulin and glucose metabolism, which are often associated clinically, is discussed.

  15. GTPases in intracellular trafficking: an overview.

    PubMed

    Segev, Nava

    2011-02-01

    Small GTPases that belong to the ras sub-families of Rab, Arf, and Rho, and the large GTPase dynamin, regulate intracellular trafficking. This issue of Seminars of Cell and Developmental Biology highlights topics regarding mechanisms by which these GTPases regulate the different steps of vesicular transport: vesicle formation, scission, targeting and fusion. In addition, the emerging roles of GTPases in coordination of individual transport steps as well as coordination of intracellular trafficking with other cellular processes are reviewed. Finally, common structures and mechanisms underlying the function of the ras-like GTPases and the importance of their function to human health and disease are discussed.

  16. Open LED Illuminator: A Simple and Inexpensive LED Illuminator for Fast Multicolor Particle Tracking in Neurons

    PubMed Central

    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

  17. Vibration-rotation alchemy in acetylene (12C2H2), ? at low vibrational excitation: from high resolution spectroscopy to fast intramolecular dynamics

    NASA Astrophysics Data System (ADS)

    Perry, David S.; Miller, Anthony; Amyay, Badr; Fayt, André; Herman, Michel

    2010-04-01

    The link between energy-resolved spectra and time-resolved dynamics is explored quantitatively for acetylene (12C2H2), ? with up to 8600 cm-1 of vibrational energy. This comparison is based on the extensive and reliable knowledge of the vibration-rotation energy levels and on the model Hamiltonian used to fit them to high precision [B. Amyay, S. Robert, M. Herman, A. Fayt, B. Raghavendra, A. Moudens, J. Thiévin, B. Rowe, and R. Georges, J. Chem. Phys. 131, 114301 (2009)]. Simulated intensity borrowing features in high resolution absorption spectra and predicted survival probabilities in intramolecular vibrational redistribution (IVR) are first investigated for the v 4 + v 5 and v 3 bright states, for J = 2, 30 and 100. The dependence of the results on the rotational quantum number and on the choice of vibrational bright state reflects the interplay of three kinds of off-diagonal resonances: anharmonic, rotational l-type, and Coriolis. The dynamical quantities used to characterize the calculated time-dependent dynamics are the dilution factor φ d, the IVR lifetime τ IVR , and the recurrence time τ rec. For the two bright states v 3 + 2v 4 and 7v 4, the collisionless dynamics for thermally averaged rotational distributions at T = 27, 270 and 500 K were calculated from the available spectroscopic data. For the 7v 4 bright state, an apparent irreversible decay of is found. In all cases, the model Hamiltonian allows a detailed calculation of the energy flow among all of the coupled zeroth-order vibration-rotation states.

  18. Prolonged contraction-relaxation cycle of fast-twitch muscles in parvalbumin knockout mice.

    PubMed

    Schwaller, B; Dick, J; Dhoot, G; Carroll, S; Vrbova, G; Nicotera, P; Pette, D; Wyss, A; Bluethmann, H; Hunziker, W; Celio, M R

    1999-02-01

    The calcium-binding protein parvalbumin (PV) occurs at high concentrations in fast-contracting vertebrate muscle fibers. Its putative role in facilitating the rapid relaxation of mammalian fast-twitch muscle fibers by acting as a temporary buffer for Ca2+ is still controversial. We generated knockout mice for PV (PV -/-) and compared the Ca2+ transients and the dynamics of contraction of their muscles with those from heterozygous (PV +/-) and wild-type (WT) mice. In the muscles of PV-deficient mice, the decay of intracellular Ca2+ concentration ([Ca2+]i) after 20-ms stimulation was slower compared with WT mice and led to a prolongation of the time required to attain peak twitch tension and to an extension of the half-relaxation time. The integral [Ca2+]i in muscle fibers of PV -/- mice was higher and consequently the force generated during a single twitch was approximately 40% greater than in PV +/- and WT animals. Acceleration of the contraction-relaxation cycle of fast-twitch muscle fibers by PV may confer an advantage in the performance of rapid, phasic movements.

  19. 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

    NASA Astrophysics Data System (ADS)

    Labiche, Jean-Claude; Mathon, Olivier; Pascarelli, Sakura; Newton, Mark A.; Ferre, Gemma Guilera; Curfs, Caroline; Vaughan, Gavin; Homs, Alejandro; Carreiras, David Fernandez

    2007-09-01

    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.

  20. 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

    SciTech Connect

    Labiche, Jean-Claude; Mathon, Olivier; Pascarelli, Sakura; Newton, Mark A.; Ferre, Gemma Guilera; Curfs, Caroline; Vaughan, Gavin; Homs, Alejandro; Carreiras, David Fernandez

    2007-09-15

    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.

  1. Intracellular Trafficking in Drosophila Visual System Development: A Basis for Pattern Formation Through Simple Mechanisms

    PubMed Central

    Chan, Chih-Chiang; Epstein, Daniel; Hiesinger, P. Robin

    2012-01-01

    Intracellular trafficking underlies cellular functions ranging from membrane remodeling to receptor activation. During multicellular organ development, these basic cell biological functions are required as both passive machinery and active signaling regulators. Exocytosis, endocytosis, and recycling of several key signaling receptors have long been known to actively regulate morphogenesis and pattern formation during Drosophila eye development. Hence, intracellular membrane trafficking not only sets the cell biological stage for receptor-mediated signaling but also actively controls signaling through spatiotemporally regulated receptor localization. In contrast to eye development, the role of intracellular trafficking for the establishment of the eye-to-brain connectivity map has only recently received more attention. It is still poorly understood how guidance receptors are spatiotemporally regulated to serve as meaningful synapse formation signals. Yet, the Drosophila visual system provides some of the most striking examples for the regulatory role of intracellular trafficking during multicellular organ development. In this review we will first highlight the experimental and conceptual advances that motivate the study of intracellular trafficking during Drosophila visual system development. We will then illuminate the development of the eye, the eye-to-brain connectivity map and the optic lobe from the perspective of cell biological dynamics. Finally, we provide a conceptual framework that seeks to explain how the interplay of simple genetically encoded intracellular trafficking events governs the seemingly complex cellular behaviors, which in turn determine the developmental product. PMID:21714102

  2. Model-based control of the temporal patterns of intracellular signaling in silico

    PubMed Central

    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

  3. Advance Liquid Metal Reactor Discrete Dynamic Event Tree/Bayesian Network Analysis and Incident Management Guidelines (Risk Management for Sodium Fast Reactors)

    SciTech Connect

    Denman, Matthew R.; Groth, Katrina M.; Cardoni, Jeffrey N.; Wheeler, Timothy A.

    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.

  4. Quantitation of hydrogen peroxide fluctuations and their modulation of dopamine dynamics in the rat dorsal striatum using fast-scan cyclic voltammetry.

    PubMed

    Spanos, Marina; Gras-Najjar, Julie; Letchworth, Jeremy M; Sanford, Audrey L; Toups, J Vincent; Sombers, Leslie A

    2013-05-15

    The dopaminergic neurons of the nigrostriatal dopamine (DA) projection from the substantia nigra to the dorsal striatum become dysfunctional and slowly degenerate in Parkinson's disease, a neurodegenerative disorder that afflicts more than one million Americans. There is no specific known cause for idiopathic Parkinson's disease; however, multiple lines of evidence implicate oxidative stress as an underlying factor in both the initiation and progression of the disease. This involves the enhanced generation of reactive oxygen species, including hydrogen peroxide (H2O2), whose role in complex biological processes is not well understood. Using fast-scan cyclic voltammetry at bare carbon-fiber microelectrodes, we have simultaneously monitored and quantified H2O2 and DA fluctuations in intact striatal tissue under basal conditions and in response to the initiation of oxidative stress. Furthermore, we have assessed the effect of acute increases in local H2O2 concentration on both electrically evoked DA release and basal DA levels. Increases in endogenous H2O2 in the dorsal striatum attenuated electrically evoked DA release, and also decreased basal DA levels in this brain region. These novel results will help to disambiguate the chemical mechanisms underlying the progression of neurodegenerative disease states, such as Parkinson's disease, that involve oxidative stress.

  5. Dynamic 1.5-T vs 3-T true fast imaging with steady-state precession (trueFISP)-MRI sequences for assessment of velopharyngeal function

    PubMed Central

    Sinko, K; Czerny, C; Jagsch, R; Baumann, A

    2015-01-01

    Objectives: To compare the image quality of MRI scans produced with 1.5- and 3.0-T devices during functional test condition. Methods: 65 MRI scans obtained with 1.5- (n = 43) or 3.0-T (n = 22) true fast imaging with steady-state precession (trueFISP) sequences from patients with a history of a cleft palate were evaluated. Two experts assessed the MRI scans, independently of each other, and blinded to the MRI technique used. Subjective ratings were entered on a five-point Likert scale. The median planes of three anatomical structures (velum, tongue and pharyngeal wall) were assessed in three functional states (at rest, during phonation of sustained “e” and during articulation of “kkk”). In addition, MRI scans taken during velopharyngeal closure were evaluated. Results: Under blinded conditions, both observers (radiologist and orthodontist) independently rated the quality of 1.5-T scans higher than that of 3.0 T. Statistical analysis of pooled data showed that the differences were highly significant (p < 0.009) in 4 out of 10 test conditions. The greatest differences in favour of 1.5 T were observed for MRI scans of the velum. Conclusions: 1.5 T used with trueFISP may be preferable over 3.0-T trueFISP for the evaluation of the velopharyngeal structures in the clinical routine. PMID:26090932

  6. [Magnetic nanoparticles and intracellular delivery of biopolymers].

    PubMed

    Kornev, A A; Dubina, M V

    2014-03-01

    The basic methods of intracellular delivery of biopolymers are present in this review. The structure and synthesis of magnetic nanoparticles, their stabilizing surfactants are described. The examples of the interaction of nanoparticles with biopolymers such as nucleic acids and proteins are considered. The final part of the review is devoted to problems physiology and biocompatibility of magnetic nanoparticles.

  7. Activities of Antimicrobial Agents against Intracellular Pneumococci

    PubMed Central

    Mandell, Gerald L.; Coleman, Elizabeth J.

    2000-01-01

    Pneumococci can enter and survive inside human lung alveolar carcinoma cells. We examined the activity of azithromycin, gentamicin, levofloxacin, moxifloxacin, penicillin G, rifampin, telithromycin, and trovafloxacin against pneumococci inside and outside cells. We found that moxifloxacin, trovafloxacin, and telithromycin were the most active, but only telithromycin killed all intracellular organisms. PMID:10952618

  8. Histoplasma capsulatum surmounts obstacles to intracellular pathogenesis

    PubMed Central

    Garfoot, Andrew L.; Rappleye, Chad A.

    2016-01-01

    The fungal pathogen Histoplasma capsulatum causes respiratory and disseminated disease, even in immunocompetent hosts. In contrast to opportunistic pathogens, which are readily controlled by phagocytic cells, H. capsulatum yeasts are able to infect macrophages, survive antimicrobial defenses, and proliferate as an intracellular pathogen. In this review, we discuss some of the molecular mechanisms that enable H. capsulatum yeasts to overcome obstacles to intracellular pathogenesis. H. capsulatum yeasts gain refuge from extracellular obstacles such as antimicrobial lung surfactant proteins by engaging the β-integrin family of phagocytic receptors to promote entry into macrophages. In addition, H. capsulatum yeasts conceal immunostimulatory β-glucans to avoid triggering signaling receptors such as the β-glucan receptor Dectin-1. H. capsulatum yeasts counteract phagocyte-produced reactive oxygen species by expression of oxidative stress defense enzymes including an extracellular superoxide dismutase and an extracellular catalase. Within the phagosome, H. capsulatum yeasts block phagosome acidification, acquire essential metals such as iron and zinc, and utilize de novo biosynthesis pathways to overcome nutritional limitations. These mechanisms explain how H. capsulatum yeasts avoid and negate macrophage defense strategies and establish a hospitable intracellular niche, making H. capsulatum a successful intracellular pathogen of macrophages. PMID:26235362

  9. Molecular dynamics simulation of the thermodynamic and transport properties of the molten salt fast reactor fuel LiF-ThF4

    NASA Astrophysics Data System (ADS)

    Dewan, Leslie C.; Simon, Christian; Madden, Paul A.; Hobbs, Linn W.; Salanne, Mathieu

    2013-03-01

    The local structure and transport properties of molten LiF-ThF4 at the eutectic composition have been studied at a range of temperatures, using molecular dynamics simulations that incorporate dipole polarization effects. This polarizable interaction potential was parameterized from first-principles calculations. We have calculated the density, self-diffusion coefficients, electrical conductivity, viscosity, and heat capacity at a range of temperatures from 850 K to 1273 K. We have also examined the changes in coordination number as a function of temperature. The simulation results were in good agreement with available experimental data, indicating that such simulations can fulfill a valuable role in augmenting existing experimental work.

  10. Intracellular calcium movements of boar spermatozoa during 'in vitro' capacitation and subsequent acrosome exocytosis follow a multiple-storage place, extracellular calcium-dependent model.

    PubMed

    Yeste, M; Fernández-Novell, J M; Ramió-Lluch, L; Estrada, E; Rocha, L G; Cebrián-Pérez, J A; Muiño-Blanco, T; Concha, I I; Ramírez, A; Rodríguez-Gil, J E

    2015-07-01

    This work analysed intracellular calcium stores of boar spermatozoa subjected to 'in vitro' capacitation (IVC) and subsequent progesterone-induced acrosome exocytosis (IVAE). Intracellular calcium was analysed through two calcium markers with different physico-chemical properties, Fluo-3 and Rhod-5N. Indicative parameters of IVC and IVAE were also evaluated. Fluo-3 was located at both the midpiece and the whole head. Rhod-5N was present at the sperm head. This distribution did not change in any of the assayed conditions. Induction of IVC was concomitant with an increase in both head and midpiece Ca(2+) signals. Additionally, while IVC induction was concurrent with a significant (p < 0.05) increase in sperm membrane permeability, no significant changes were observed in O2 consumption and ATP levels. Incubation of boar spermatozoa in the absence of calcium showed a loss of both Ca(2+) labellings concomitantly with the sperm's inability to achieve IVC. The absence of extracellular calcium also induced a severe decrease in the percentage of spermatozoa exhibiting high mitochondrial membrane potential (hMMP). The IVAE was accompanied by a fast increase in both Ca(2+) signalling in control spermatozoa. These peaks were either not detected or much lessened in the absence of calcium. Remarkably, Fluo-3 marking at the midpiece increased after progesterone addition to sperm cells incubated in a medium without Ca(2+) . The simultaneous addition of progesterone with the calcium chelant EGTA inhibited IVAE, and this was accompanied by a significant (p < 0.05) decrease in the intensity of progesterone Ca(2+) -induced peak, O2 consumption and ATP levels. Our results suggest that boar spermatozoa present different calcium deposits with a dynamic equilibrium among them and with the extracellular environment. Additionally, the modulation role of the intracellular calcium in spermatozoa function seems to rely on its precise localization in boar spermatozoa.

  11. Is it growing exponentially fast? -- Impact of assuming exponential growth for characterizing and forecasting epidemics with initial near-exponential growth dynamics.

    PubMed

    Chowell, Gerardo; Viboud, Cécile

    2016-10-01

    The increasing use of mathematical models for epidemic forecasting has highlighted the importance of designing models that capture the baseline transmission characteristics in order to generate reliable epidemic forecasts. Improved models for epidemic forecasting could be achieved by identifying signature features of epidemic growth, which could inform the design of models of disease spread and reveal important characteristics of the transmission process. In particular, it is often taken for granted that the early growth phase of different growth processes in nature follow early exponential growth dynamics. In the context of infectious disease spread, this assumption is often convenient to describe a transmission process with mass action kinetics using differential equations and generate analytic expressions and estimates of the reproduction number. In this article, we carry out a simulation study to illustrate the impact of incorrectly assuming an exponential-growth model to characterize the early phase (e.g., 3-5 disease generation intervals) of an infectious disease outbreak that follows near-exponential growth dynamics. Specifically, we assess the impact on: 1) goodness of fit, 2) bias on the growth parameter, and 3) the impact on short-term epidemic forecasts. Designing transmission models and statistical approaches that more flexibly capture the profile of epidemic growth could lead to enhanced model fit, improved estimates of key transmission parameters, and more realistic epidemic forecasts.

  12. Land Use Dynamics of the Fast-Growing Shanghai Metropolis, China (1979–2008) and its Implications for Land Use and Urban Planning Policy

    PubMed Central

    Zhang, Hao; Zhou, Li-Guo; Chen, Ming-Nan; Ma, Wei-Chun

    2011-01-01

    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. PMID:22319382

  13. Land use dynamics of the fast-growing Shanghai Metropolis, China (1979-2008) and its implications for land use and urban planning policy.

    PubMed

    Zhang, Hao; Zhou, Li-Guo; Chen, Ming-Nan; Ma, Wei-Chun

    2011-01-01

    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.

  14. Fast relaxation of coarse-grained models of polymer interphases by hybrid particle-field molecular dynamics: Polystyrene-silica nanocomposites as an example

    NASA Astrophysics Data System (ADS)

    De Nicola, Antonio; Kawakatsu, Toshihiro; Müller-Plathe, Florian; Milano, Giuseppe

    2016-10-01

    Polymer composites attract large attention for their industrial use because of their unique features. The preparation of equilibrated melts of long entangled chains in the presence of a solid nanoparticle in molecular dynamics simulations is a very difficult task due to the slow relaxation time. We present a coarse-grained (CG) model suitable for polymer nanocomposites which combines Iterative-Boltzmann-Inversion derived polymer models, the hybrid particle-field representation of non-bonded interactions, and a convenient description of a solid nanoparticle suitable for hybrid particle-field models. The proposed approach is applied to test simulations of well characterized polystyrene-silica nanocomposites models. Finally, procedures for an efficient relaxation of pure polymer melts and interphase structures of large molecular weight nanocomposites are proposed.

  15. Mechanism of Solid-State Thermolysis of Ammonia Boraine: 15N NMR Study Using Fast Magic-Angle Spinning and Dynamic Nuclear Polarization

    SciTech Connect

    Kobayashi, Takeshi; Gupta, Shalabh; Caporini, Marc A; Pecharsky, Vitalij K; Pruski, Marek

    2014-08-28

    The solid-state thermolysis of ammonia borane (NH3BH3, AB) was explored using state-of-the-art 15N solid-state NMR spectroscopy, including 2D indirectly detected 1H{15N} heteronuclear correlation and dynamic nuclear polarization (DNP)-enhanced 15N{1H} cross-polarization experiments as well as 11B NMR. The complementary use of 15N and 11B NMR experiments, supported by density functional theory calculations of the chemical shift tensors, provided insights into the dehydrogenation mechanism of AB—insights that have not been available by 11B NMR alone. Specifically, highly branched polyaminoborane derivatives were shown to form from AB via oligomerization in the “head-to-tail” manner, which then transform directly into hexagonal boron nitride analog through the dehydrocyclization reaction, bypassing the formation of polyiminoborane.

  16. Beam and spin dynamics in the fast ramping storage ring ELSA: Concepts and measures to increase beam energy, current and polarization

    NASA Astrophysics Data System (ADS)

    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.

  17. Structural analysis of a class III preQ1 riboswitch reveals an aptamer distant from a ribosome-binding site regulated by fast dynamics

    PubMed Central

    Liberman, Joseph A.; Suddala, Krishna C.; Aytenfisu, Asaminew; Chan, Dalen; Belashov, Ivan A.; Salim, Mohammad; Mathews, David H.; Spitale, Robert C.; Walter, Nils G.; Wedekind, Joseph E.

    2015-01-01

    PreQ1-III riboswitches are newly identified RNA elements that control bacterial genes in response to preQ1 (7-aminomethyl-7-deazaguanine), a precursor to the essential hypermodified tRNA base queuosine. Although numerous riboswitches fold as H-type or HLout-type pseudoknots that integrate ligand-binding and regulatory sequences within a single folded domain, the preQ1-III riboswitch aptamer forms a HLout-type pseudoknot that does not appear to incorporate its ribosome-binding site (RBS). To understand how this unusual organization confers function, we determined the crystal structure of the class III preQ1 riboswitch from Faecalibacterium prausnitzii at 2.75 Å resolution. PreQ1 binds tightly (KD,app 6.5 ± 0.5 nM) between helices P1 and P2 of a three-way helical junction wherein the third helix, P4, projects orthogonally from the ligand-binding pocket, exposing its stem-loop to base pair with the 3′ RBS. Biochemical analysis, computational modeling, and single-molecule FRET imaging demonstrated that preQ1 enhances P4 reorientation toward P1–P2, promoting a partially nested, H-type pseudoknot in which the RBS undergoes rapid docking (kdock ∼0.6 s−1) and undocking (kundock ∼1.1 s−1). Discovery of such dynamic conformational switching provides insight into how a riboswitch with bipartite architecture uses dynamics to modulate expression platform accessibility, thus expanding the known repertoire of gene control strategies used by regulatory RNAs. PMID:26106162

  18. Structural analysis of a class III preQ1 riboswitch reveals an aptamer distant from a ribosome-binding site regulated by fast dynamics.

    PubMed

    Liberman, Joseph A; Suddala, Krishna C; Aytenfisu, Asaminew; Chan, Dalen; Belashov, Ivan A; Salim, Mohammad; Mathews, David H; Spitale, Robert C; Walter, Nils G; Wedekind, Joseph E

    2015-07-07

    PreQ1-III riboswitches are newly identified RNA elements that control bacterial genes in response to preQ1 (7-aminomethyl-7-deazaguanine), a precursor to the essential hypermodified tRNA base queuosine. Although numerous riboswitches fold as H-type or HLout-type pseudoknots that integrate ligand-binding and regulatory sequences within a single folded domain, the preQ1-III riboswitch aptamer forms a HLout-type pseudoknot that does not appear to incorporate its ribosome-binding site (RBS). To understand how this unusual organization confers function, we determined the crystal structure of the class III preQ1 riboswitch from Faecalibacterium prausnitzii at 2.75 Å resolution. PreQ1 binds tightly (KD,app 6.5 ± 0.5 nM) between helices P1 and P2 of a three-way helical junction wherein the third helix, P4, projects orthogonally from