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Sample records for fast intracellular dynamics

  1. Fast-Response Calmodulin-Based Fluorescent Indicators Reveal Rapid Intracellular Calcium Dynamics.

    PubMed

    Helassa, Nordine; Zhang, Xiao-hua; Conte, Ianina; Scaringi, John; Esposito, Elric; Bradley, Jonathan; Carter, Thomas; Ogden, David; Morad, Martin; Török, Katalin

    2015-11-03

    Faithful reporting of temporal patterns of intracellular Ca(2+) dynamics requires the working range of indicators to match the signals. Current genetically encoded calmodulin-based fluorescent indicators are likely to distort fast Ca(2+) signals by apparent saturation and integration due to their limiting fluorescence rise and decay kinetics. A series of probes was engineered with a range of Ca(2+) affinities and accelerated kinetics by weakening the Ca(2+)-calmodulin-peptide interactions. At 37 °C, the GCaMP3-derived probe termed GCaMP3fast is 40-fold faster than GCaMP3 with Ca(2+) decay and rise times, t1/2, of 3.3 ms and 0.9 ms, respectively, making it the fastest to-date. GCaMP3fast revealed discreet transients with significantly faster Ca(2+) dynamics in neonatal cardiac myocytes than GCaMP6f. With 5-fold increased two-photon fluorescence cross-section for Ca(2+) at 940 nm, GCaMP3fast is suitable for deep tissue studies. The green fluorescent protein serves as a reporter providing important novel insights into the kinetic mechanism of target recognition by calmodulin. Our strategy to match the probe to the signal by tuning the affinity and hence the Ca(2+) kinetics of the indicator is applicable to the emerging new generations of calmodulin-based probes.

  2. Fast-Response Calmodulin-Based Fluorescent Indicators Reveal Rapid Intracellular Calcium Dynamics

    PubMed Central

    Helassa, Nordine; Zhang, Xiao-hua; Conte, Ianina; Scaringi, John; Esposito, Elric; Bradley, Jonathan; Carter, Thomas; Ogden, David; Morad, Martin; Török, Katalin

    2015-01-01

    Faithful reporting of temporal patterns of intracellular Ca2+ dynamics requires the working range of indicators to match the signals. Current genetically encoded calmodulin-based fluorescent indicators are likely to distort fast Ca2+ signals by apparent saturation and integration due to their limiting fluorescence rise and decay kinetics. A series of probes was engineered with a range of Ca2+ affinities and accelerated kinetics by weakening the Ca2+-calmodulin-peptide interactions. At 37 °C, the GCaMP3-derived probe termed GCaMP3fast is 40-fold faster than GCaMP3 with Ca2+ decay and rise times, t1/2, of 3.3 ms and 0.9 ms, respectively, making it the fastest to-date. GCaMP3fast revealed discreet transients with significantly faster Ca2+ dynamics in neonatal cardiac myocytes than GCaMP6f. With 5-fold increased two-photon fluorescence cross-section for Ca2+ at 940 nm, GCaMP3fast is suitable for deep tissue studies. The green fluorescent protein serves as a reporter providing important novel insights into the kinetic mechanism of target recognition by calmodulin. Our strategy to match the probe to the signal by tuning the affinity and hence the Ca2+ kinetics of the indicator is applicable to the emerging new generations of calmodulin-based probes. PMID:26527405

  3. Dynamics of intracellular information decoding

    NASA Astrophysics Data System (ADS)

    Kobayashi, Tetsuya J.; Kamimura, Atsushi

    2011-10-01

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

  4. Intracellular Pressure Dynamics in Blebbing Cells.

    PubMed

    Strychalski, Wanda; Guy, Robert D

    2016-03-01

    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. PMID:26958893

  5. Dynamics of gradient formation by intracellular shuttling

    NASA Astrophysics Data System (ADS)

    Berezhkovskii, Alexander M.; Shvartsman, Stanislav Y.

    2015-08-01

    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.

  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

    NASA Astrophysics Data System (ADS)

    Restrepo, Juan G.; Karma, Alain

    2009-09-01

    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.

  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. Intracellular Ca(2+) dynamics and the stability of ventricular tachycardia.

    PubMed Central

    Chudin, E; Goldhaber, J; Garfinkel, A; Weiss, J; Kogan, B

    1999-01-01

    Ventricular fibrillation (VF), the major cause of sudden cardiac death, is typically preceded by ventricular tachycardia (VT), but the mechanisms underlying the transition from VT to VF are poorly understood. Intracellular Ca(2+) overload occurs during rapid heart rates typical of VT and is also known to promote arrhythmias. We therefore studied the role of intracellular Ca(2+) dynamics in the transition from VT to VF, using a combined experimental and mathematical modeling approach. Our results show that 1) rapid pacing of rabbit ventricular myocytes at 35 degrees C led to increased intracellular Ca(2+) levels and complex patterns of action potential (AP) configuration and the intracellular Ca(2+) transients; 2) the complex patterns of the Ca(2+) transient arose directly from the dynamics of intracellular Ca(2+) cycling, and were not merely passive responses to beat-to-beat alterations in AP; 3) the complex Ca(2+) dynamics were simulated in a modified version of the Luo-Rudy (LR) ventricular action potential with improved intracellular Ca(2+) dynamics, and showed good agreement with the experimental findings in isolated myocytes; and 4) when incorporated into simulated two-dimensional cardiac tissue, this action potential model produced a form of spiral wave breakup from VT to a VF-like state in which intracellular Ca(2+) dynamics played a key role through its influence on Ca(2+)-sensitive membrane currents such as I(Ca), I(NaCa), and I(ns(Ca)). To the extent that spiral wave breakup is useful as a model for the transition from VT to VF, these findings suggest that intracellular Ca(2+) dynamics may play an important role in the destabilization of VT and its degeneration into VF. PMID:10585917

  10. 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.

  11. Contributions of intracellular ions to kv channel voltage sensor dynamics.

    PubMed

    Goodchild, Samuel J; Fedida, David

    2012-01-01

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

  12. Protein-coat dynamics and cluster phases in intracellular trafficking

    NASA Astrophysics Data System (ADS)

    Huber, Greg; Wang, Hui; Mukhopadhyay, Ranjan

    2011-09-01

    Clustering of membrane proteins is a hallmark of biological membranes' lateral organization and crucial to their function. However, the physical properties of these protein aggregates remain poorly understood. Ensembles of coat proteins, the example considered here, are necessary for intracellular transport in eukaryotic cells. Assembly and disassembly rates for coat proteins involved in intracellular vesicular trafficking must be carefully controlled: their assembly deforms the membrane patch and drives vesicle formation, yet the protein coat must rapidly disassemble after vesiculation. Motivated by recent experimental findings for protein-coat dynamics, we study a dynamical Ising-type model for coat assembly and disassembly, and demonstrate how simple dynamical rules generate a robust, steady-state distribution of protein clusters (corresponding to intermediate budded shapes) and how cluster sizes are controlled by the kinetics. We interpret the results in terms of both vesiculation and the coupling to cargo proteins.

  13. 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.

  14. 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.

  15. 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.

  16. Intracellular Demography and the Dynamics of Salmonella enterica Infections

    PubMed Central

    Sheppard, Mark; Grant, Andrew J; Maskell, Duncan J; Grenfell, Bryan T; Mastroeni, Pietro

    2006-01-01

    An understanding of within-host dynamics of pathogen interactions with eukaryotic cells can shape the development of effective preventive measures and drug regimes. Such investigations have been hampered by the difficulty of identifying and observing directly, within live tissues, the multiple key variables that underlay infection processes. Fluorescence microscopy data on intracellular distributions of Salmonella enterica serovar Typhimurium (S. Typhimurium) show that, while the number of infected cells increases with time, the distribution of bacteria between cells is stationary (though highly skewed). Here, we report a simple model framework for the intensity of intracellular infection that links the quasi-stationary distribution of bacteria to bacterial and cellular demography. This enables us to reject the hypothesis that the skewed distribution is generated by intrinsic cellular heterogeneities, and to derive specific predictions on the within-cell dynamics of Salmonella division and host-cell lysis. For within-cell pathogens in general, we show that within-cell dynamics have implications across pathogen dynamics, evolution, and control, and we develop novel generic guidelines for the design of antibacterial combination therapies and the management of antibiotic resistance. PMID:17048989

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

    PubMed

    Vesely, P; Boyde, A

    2001-06-01

    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 microm and in time to 1/25th of a second. Mapping the cell space at 0.2 microm x 0.2 microm (XY = in instantaneous best focal plane) x 0.5 microm (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.

  18. Mitochondrial dynamics and their intracellular traffic in porcine oocytes.

    PubMed

    Yamochi, T; Hashimoto, S; Amo, A; Goto, H; Yamanaka, M; Inoue, M; Nakaoka, Y; Morimoto, Y

    2016-08-01

    Meiotic maturation of oocytes requires a variety of ATP-dependent reactions, such as germinal vesicle breakdown, spindle formation, and rearrangement of plasma membrane structure, which is required for fertilization. Mitochondria are accordingly expected be localized to subcellular sites of energy utilization. Although microtubule-dependent cellular traffic for mitochondria has been studied extensively in cultured neuronal (and some other somatic) cells, the molecular mechanism of their dynamics in mammalian oocytes at different stages of maturation remains obscure. The present work describes dynamic aspects of mitochondria in porcine oocytes at the germinal vesicle stage. After incubation of oocytes with MitoTracker Orange followed by centrifugation, mitochondria-enriched ooplasm was obtained using a glass needle and transferred into a recipient oocyte. The intracellular distribution of the fluorescent mitochondria was then observed over time using a laser scanning confocal microscopy equipped with an incubator. Kinetic analysis revealed that fluorescent mitochondria moved from central to subcortical areas of oocytes and were dispersed along plasma membranes. Such movement of mitochondria was inhibited by either cytochalasin B or cytochalasin D but not by colcemid, suggesting the involvement of microfilaments. This method of visualizing mitochondrial dynamics in live cells permits study of the pathophysiology of cytoskeleton-dependent intracellular traffic of mitochondria and associated energy metabolism during meiotic maturation of oocytes.

  19. 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.

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

    PubMed

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

    2016-01-01

    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. PMID:27004604

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

    PubMed Central

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

    2016-01-01

    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. PMID:27004604

  2. Neocortical very fast oscillations (ripples, 80-200 Hz) during seizures: intracellular correlates.

    PubMed

    Grenier, François; Timofeev, Igor; Steriade, Mircea

    2003-02-01

    Multi-site field potential and intracellular recordings from various neocortical areas were used to study very fast oscillations or ripples (80-200 Hz) during electrographic seizures in cats under ketamine-xylazine anesthesia. The animals displayed spontaneously occurring and electrically induced seizures comprising spike-wave complexes (2-3 Hz) and fast runs (10-20 Hz). Neocortical ripples had much higher amplitudes during seizures than during the slow oscillation preceding the onset of seizures. A series of experimental data from the present study supports the hypothesis that ripples are implicated in seizure initiation. Ripples were particularly strong at the onset of seizures and halothane, which antagonizes the occurrence of ripples, also blocked seizures. The firing of electrophysiologically defined cellular types was phase-locked with ripples in simultaneously recorded field potentials. This indicates that ripples during paroxysmal events are associated with a coordination of firing in a majority of neocortical neurons. This was confirmed with dual intracellular recordings. Based on the amplitude that neocortical ripples reach during paroxysmal events, we propose a mechanism by which neocortical ripples during normal network activity could actively participate in the initiation of seizures on reaching a certain threshold amplitude. This mechanism involves a vicious feedback loop in which very fast oscillations in field potentials are a reflection of synchronous action potentials, and in turn these oscillations help generate and synchronize action potentials in adjacent neurons through electrical interactions.

  3. Fast internal dynamics in alcohol dehydrogenase.

    PubMed

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

    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 D2O solvent. It is tempting to associate the fast internal process with solvent exposed amino acid residues with dangling side chains. PMID:26298156

  4. 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.

  5. 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

  6. 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.

  7. Understanding anomalous delays in a model of intracellular calcium dynamics

    NASA Astrophysics Data System (ADS)

    Harvey, Emily; Kirk, Vivien; Osinga, Hinke M.; Sneyd, James; Wechselberger, Martin

    2010-12-01

    In many cell types, oscillations in the concentration of free intracellular calcium ions are used to control a variety of cellular functions. It has been suggested [J. Sneyd et al., "A method for determining the dependence of calcium oscillations on inositol trisphosphate oscillations," Proc. Natl. Acad. Sci. U.S.A. 103, 1675-1680 (2006)] that the mechanisms underlying the generation and control of such oscillations can be determined by means of a simple experiment, whereby a single exogenous pulse of inositol trisphosphate (IP3) is applied to the cell. However, more detailed mathematical investigations [M. Domijan et al., "Dynamical probing of the mechanisms underlying calcium oscillations," J. Nonlinear Sci. 16, 483-506 (2006)] have shown that this is not necessarily always true, and that the experimental data are more difficult to interpret than first thought. Here, we use geometric singular perturbation techniques to study the dynamics of models that make different assumptions about the mechanisms underlying the calcium oscillations. In particular, we show how recently developed canard theory for singularly perturbed systems with three or more slow variables [M. Wechselberger, "A propos de canards (Apropos canards)," Preprint, 2010] applies to these calcium models and how the presence of a curve of folded singularities and corresponding canards can result in anomalous delays in the response of these models to a pulse of IP3.

  8. Fast bubble dynamics and sizing

    NASA Astrophysics Data System (ADS)

    Czarnecki, Krzysztof; Fouan, Damien; Achaoui, Younes; Mensah, Serge

    2015-11-01

    Single bubble sizing is usually performed by measuring the resonant bubble response using the Dual Frequency Ultrasound Method. However, in practice, the use of millisecond-duration chirp-like waves yields nonlinear distortions of the bubble oscillations. In comparison with the resonant curve obtained under harmonic excitation, it was observed that the bubble dynamic response shifted by up to 20 percent of the resonant frequency with bubble radii of less than 100 μm. In the case of low pressure waves (P < 5 kPa), an approximate formula for the apparent frequency shift is derived. Simulated and experimental bubble responses are analyzed in the time-frequency domain using an enhanced concentrated (reassigned) spectrogram. The difference in the resonant frequency resulted from the persistence of the resonant mode in the bubble response. Numerical simulations in which these findings are extended to pairs of coupled bubbles and to bubble clouds are also presented.

  9. 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

  10. 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

  11. 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)

  12. Slow dynamics and anomalous nonlinear fast dynamics in diverse solids.

    PubMed

    Johnson, Paul; Sutin, Alexander

    2005-01-01

    Results are reported of the first systematic study of anomalous nonlinear fast dynamics and slow dynamics in a number of solids. Observations are presented from seven diverse materials showing that anomalous nonlinear fast dynamics (ANFD) and slow dynamics (SD) occur together, significantly expanding the nonlinear mesoscopic elasticity class. The materials include samples of gray iron, alumina ceramic, quartzite, cracked Pyrex, marble, sintered metal, and perovskite ceramic. In addition, it is shown that materials which exhibit ANFD have very similar ratios of amplitude-dependent internal-friction to the resonance-frequency shift with strain amplitude. The ratios range between 0.28 and 0.63, except for cracked Pyrex glass, which exhibits a ratio of 1.1, and the ratio appears to be a material characteristic. The ratio of internal friction to resonance frequency shift as a function of time during SD is time independent, ranging from 0.23 to 0.43 for the materials studied. PMID:15704405

  13. Slow dynamics and anomalous nonlinear fast dynamics in diverse solids

    NASA Astrophysics Data System (ADS)

    Johnson, Paul; Sutin, Alexander

    2005-01-01

    Results are reported of the first systematic study of anomalous nonlinear fast dynamics and slow dynamics in a number of solids. Observations are presented from seven diverse materials showing that anomalous nonlinear fast dynamics (ANFD) and slow dynamics (SD) occur together, significantly expanding the nonlinear mesoscopic elasticity class. The materials include samples of gray iron, alumina ceramic, quartzite, cracked Pyrex, marble, sintered metal, and perovskite ceramic. In addition, it is shown that materials which exhibit ANFD have very similar ratios of amplitude-dependent internal-friction to the resonance-frequency shift with strain amplitude. The ratios range between 0.28 and 0.63, except for cracked Pyrex glass, which exhibits a ratio of 1.1, and the ratio appears to be a material characteristic. The ratio of internal friction to resonance frequency shift as a function of time during SD is time independent, ranging from 0.23 to 0.43 for the materials studied. .

  14. 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...

  15. 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

  16. Live Imaging of Intracellular Dynamics During Meiotic Maturation in Mouse Oocytes.

    PubMed

    Yoshida, Shuhei; Sakakibara, Yogo; Kitajima, Tomoya S

    2016-01-01

    Fluorescence live imaging is a powerful approach to study intracellular dynamics during cellular events such as cell division. By applying automated confocal live imaging to mouse oocytes, in which meiotic maturation can be induced in vitro after the introduction of fluorescent proteins through microinjection, the meiotic dynamics of intracellular structures, such as chromosomes, can be monitored at high resolution. A combination of this method with approaches for the perturbation of specific proteins opens up opportunities for understanding the molecular and intracellular basis of mammalian meiosis. PMID:27557586

  17. Intracellular Dynamics of Synucleins: "Here, There and Everywhere".

    PubMed

    Surguchov, Andrei

    2015-01-01

    Synucleins are small, soluble proteins expressed primarily in neural tissue and in certain tumors. The synuclein family consists of three members: α-, β-, and γ-synucleins present only in vertebrates. Members of the synuclein family have high sequence identity, especially in the N-terminal regions. The synuclein gene family came into the spotlight, when one of its members, α-synuclein, was found to be associated with Parkinson's disease and other neurodegenerative disorders, whereas γ-synuclein was linked to several forms of cancer. There are a lot of controversy and exciting debates concerning members of the synuclein family, including their normal functions, toxicity, role in pathology, transmission between cells and intracellular localization. Important findings which remain undisputable for many years are synuclein localization in synapses and their role in the regulation of synaptic vesicle trafficking, whereas their presence and function in mitochondria and nucleus is a debated topic. In this review, we present the data on the localization of synucleins in two intracellular organelles: the nucleus and mitochondria. PMID:26614873

  18. Introduction to focus issue: intracellular Ca2+ dynamics--a change of modeling paradigm?

    PubMed

    Falcke, Martin

    2009-09-01

    Intracellular Ca(2+) concentration dynamics have been perceived as a prototypical deterministic intracellular reaction-diffusion system in biophysics for many years. Recent experimental findings challenge that view and suggest them to be fluctuation driven. That renders this system interesting for nonlinear physics, in general, since we can study the emergence of macroscopic behavior from mesoscopic dynamics. In particular, we can observe the random elemental events, called puffs, and the macroscopic pattern with the same experimental means. Here, we give a short introduction to the current discussion on theoretical and modeling concepts, and this Focus Issue reflecting it. PMID:19792027

  19. A fast dynamic mode in rare earth based glasses

    NASA Astrophysics Data System (ADS)

    Zhao, L. Z.; Xue, R. J.; Zhu, Z. G.; Ngai, K. L.; Wang, W. H.; Bai, H. Y.

    2016-05-01

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

  20. 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

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

    PubMed

    Rawson, Frankie J; Hicks, Jacqueline; Dodd, Nicholas; Abate, Wondwossen; Garrett, David J; Yip, Nga; Fejer, Gyorgy; Downard, Alison J; Baronian, Kim H R; Jackson, Simon K; Mendes, Paula M

    2015-10-28

    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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

    2016-10-01

    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.

  8. Joint effects of mitosis and intracellular delay on viral dynamics: two-parameter bifurcation analysis.

    PubMed

    Li, Michael Y; Shu, Hongying

    2012-05-01

    To understand joint effects of logistic growth in target cells and intracellular delay on viral dynamics in vivo, we carry out two-parameter bifurcation analysis of an in-host model that describes infections of many viruses including HIV-I, HBV and HTLV-I. The bifurcation parameters are the mitosis rate r of the target cells and an intracellular delay τ in the incidence of viral infection. We describe the stability region of the chronic-infection equilibrium E* in the two-dimensional (r, τ) parameter space, as well as the global Hopf bifurcation curves as each of τ and r varies. Our analysis shows that, while both τ and r can destabilize E* and cause Hopf bifurcations, they do behave differently. The intracellular delay τ can cause Hopf bifurcations only when r is positive and sufficiently large, while r can cause Hopf bifurcations even when τ = 0. Intracellular delay τ can cause stability switches in E* while r does not.

  9. Free-Standing Kinked Silicon Nanowires for Probing Inter- and Intracellular Force Dynamics.

    PubMed

    Zimmerman, John F; Murray, Graeme F; Wang, Yucai; Jumper, John M; Austin, Jotham R; Tian, Bozhi

    2015-08-12

    Silicon nanowires (SiNWs) have emerged as a new class of materials with important applications in biology and medicine with current efforts having focused primarily on using substrate bound SiNW devices. However, developing devices capable of free-standing inter- and intracellular operation is an important next step in designing new synthetic cellular materials and tools for biophysical characterization. To demonstrate this, here we show that label free SiNWs can be internalized in multiple cell lines, forming robust cytoskeletal interfaces, and when kinked can serve as free-standing inter- and intracellular force probes capable of continuous extended (>1 h) force monitoring. Our results show that intercellular interactions exhibit ratcheting like behavior with force peaks of ∼69.6 pN/SiNW, while intracellular force peaks of ∼116.9 pN/SiNW were recorded during smooth muscle contraction. To accomplish this, we have introduced a simple single-capture dark-field/phase contrast optical imaging modality, scatter enhanced phase contrast (SEPC), which enables the simultaneous visualization of both cellular components and inorganic nanostructures. This approach demonstrates that rationally designed devices capable of substrate-independent operation are achievable, providing a simple and scalable method for continuous inter- and intracellular force dynamics studies.

  10. 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

    2012-12-01

    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.

  11. 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.

  12. 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

  13. Subcellular Dynamics of Multifunctional Protein Regulation: Mechanisms of GAPDH Intracellular Translocation

    PubMed Central

    Sirover, Michael A.

    2012-01-01

    Multidimensional proteins such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) exhibit distinct activities unrelated to their originally identified functions. Apart from glycolysis, GAPDH participates in iron metabolism, membrane trafficking, histone biosynthesis, the maintenance of DNA integrity and receptor mediated cell signaling. Further, multifunctional proteins exhibit distinct changes in their subcellular localization reflecting their new activities. As such, GAPDH is not only a cytosolic protein but is localized in the membrane, the nucleus, polysomes, the ER and the Golgi. In addition, although the initial subcellular localizations of multifunctional proteins may be of significance, dynamic changes in intracellular distribution may occur as a consequence of those new activities. As such, regulatory mechanisms may exist through which cells control multifunctional protein expression as a function of their subcellular localization. The temporal sequence through which subcellular translocation and the acquisition of new GAPDH functions is considered as well as post-translational modification as a basis for its intracellular transport. PMID:22388977

  14. Dynamics of free intracellular Ca2+ during synaptic and spike activity of cricket tibial motoneurons.

    PubMed

    Baden, Tom; Hedwig, Berthold

    2009-04-01

    For all nervous systems, motoneurons are the main output pathway. They are involved in generating episodic motor activity as well as enduring motor rhythms. To determine whether changes in cytosolic Ca(2+) correlate with motor performance, we studied the spatiotemporal dynamics, mode of entry and role of free intracellular Ca(2+) in cricket (Gryllus bimaculatus) front leg tibial extensor and flexor motoneurons. Synaptic activation or intracellular depolarising current injection uniformly increased Ca(2+) with the same dynamics throughout the primary and secondary branches of the dendritic tree of all motoneurons. Ca(2+) rise times (mean tau(rise), 233-295 ms) were lower than decay times (mean tau(decay), 1927-1965 ms), and resulted in a Ca(2+) plateau during repetitive activation, such as during walking. The neurons therefore operate with a different Ca(2+) level during walking than during episodic leg movements. Ca(2+) enters the dendritic processes of motoneurons via a voltage-activated mechanism. Entry is driven by subthreshold excitation, and is largely independent of the neurons' spiking activity. To what extent ligand-activated mechanisms of Ca(2+) entry operate remains uncertain. We found no evidence for any prominent Ca(2+)-activated secondary currents in these motoneurons. Excitatory postsynaptic potentials evoked by extracellular stimulation of descending neurons were unaffected by the level of free intracellular Ca(2+). The activity of tibial motoneurons therefore appears to be only weakly dependent on the level of free intracellular Ca(2+) in dendrites. This is different to what has been found for many other neurons studied, and may represent an essential prerequisite for insect motoneurons to support a wide range of both episodic and rhythmic motor sequences underlying behaviour.

  15. 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).

  16. 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.

  17. FAST TRACK COMMUNICATION: Complexified dynamical systems

    NASA Astrophysics Data System (ADS)

    Bender, Carl M.; Holm, Darryl D.; Hook, Daniel W.

    2007-08-01

    Many dynamical systems, such as the Lotka-Volterra predator-prey model and the Euler equations for the free rotation of a rigid body, are {{\\cal P}}{{\\cal T}} symmetric. The standard and well-known real solutions to such dynamical systems constitute an infinitessimal subclass of the full set of complex solutions. This paper examines a subset of the complex solutions that contains the real solutions, namely those having {{\\cal P}}{{\\cal T}} symmetry. The condition of {{\\cal P}}{{\\cal T}} symmetry selects out complex solutions that are periodic.

  18. FAST - A multiprocessed 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

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

  19. 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.

  20. 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.

  1. Impaired Intracellular Ca2+ Dynamics in Live Cardiomyocytes Revealed by Rapid Line Scan Confocal Microscopy

    NASA Astrophysics Data System (ADS)

    Plank, David M.; Sussman, Mark A.

    2005-06-01

    Altered intracellular Ca2+ dynamics are characteristically observed in cardiomyocytes from failing hearts. Studies of Ca2+ handling in myocytes predominantly use Fluo-3 AM, a visible light excitable Ca2+ chelating fluorescent dye in conjunction with rapid line-scanning confocal microscopy. However, Fluo-3 AM does not allow for traditional ratiometric determination of intracellular Ca2+ concentration and has required the use of mathematic correction factors with values obtained from separate procedures to convert Fluo-3 AM fluorescence to appropriate Ca2+ concentrations. This study describes methodology to directly measure intracellular Ca2+ levels using inactivated, Fluo-3-AM-loaded cardiomyocytes equilibrated with Ca2+ concentration standards. Titration of Ca2+ concentration exhibits a linear relationship to increasing Fluo-3 AM fluorescence intensity. Images obtained from individual myocyte confocal scans were recorded, average pixel intensity values were calculated, and a plot is generated relating the average pixel intensity to known Ca2+ concentrations. These standard plots can be used to convert transient Ca2+ fluorescence obtained with experimental cells to Ca2+ concentrations by linear regression analysis. Standards are determined on the same microscope used for acquisition of unknown Ca2+ concentrations, simplifying data interpretation and assuring accuracy of conversion values. This procedure eliminates additional equipment, ratiometric imaging, and mathematic correction factors and should be useful to investigators requiring a straightforward method for measuring Ca2+ concentrations in live cells using Ca2+-chelating dyes exhibiting variable fluorescence intensity.

  2. 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

  3. A dynamical model of Kara Sea land-fast ice

    NASA Astrophysics Data System (ADS)

    Olason, Einar

    2016-05-01

    This paper introduces modifications to the traditional viscous-plastic sea-ice dynamical model, which are necessary to model land-fast ice in the Kara Sea in a realistic manner. The most important modifications are an increase in the maximum viscosity from the standard value of ζmax=>(2.5×108s>)P to ζmax=>(1013s>)P, and to use a solver for the momentum equation capable of correctly solving for small ice velocities (the limit here is set to 10-4 m/s). Given these modifications, a necessary condition for a realistic fast-ice simulation is that the yield curve give sufficient uniaxial compressive strength. This is consistent with the idea that land-fast ice in the Kara Sea forms primarily via static arching. The modified model is tested and tuned using forcing data and observations from 1997 and 1998. The results show that it is possible to model land-fast ice using this model with the modifications mentioned above. The model performs well in terms of modeled fast-ice extent, but suffers from unrealistic break-ups during the start and end of the fast-ice season. The main results are that fast ice in the Kara Sea is supported by arching of the ice, the arches footers resting on a chain of islands off shore.

  4. 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.

  5. 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.

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

    PubMed

    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

  7. 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

  8. Dynamic pricing? Not so fast. a residential consumer perspective

    SciTech Connect

    Alexander, Barbara R.

    2010-07-15

    With the installation of smart metering, will residential customers be moved to ''dynamic'' pricing? Some supporters of changing residential rate design from a fixed and stable rate structure believe customers should be required to take electric service with time-variant price signals. Not so fast, though. There are real implications associated with this strategy. (author)

  9. 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)

  10. 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.

  11. Laser microspectrofluorometry for measuring dynamic changes of intracellular free Ca2+ in human airway gland cells

    NASA Astrophysics Data System (ADS)

    Millot, Jean-Marc; Merten, M.; Sharonov, S.; Figarella, C.; Jacquot, J.; Manfait, Michel

    1996-01-01

    Intracellular Ca2+ is a ubiquitous second messenger that regulates a wide variety of cellular functions including secretion, transepithelial solute and fluid transport. Laser confocal microspectrofluorometry (DILOR, Lille, France) was applied to visualize fluorescence emission spectra of the Indo-1 for measuring the intracellular free Ca2+ levels ([Ca2+]i) in a human tracheal gland immortalized cell line (MM39 cell line). Under a 351 nm laser excitation (0.5 (mu) W), the intracellular spectrum was analyzed as a ratio of the emission intensities at 420 and 500 nm. Previously, the intracellular Ca2+ calibration has been performed to define the relation between the intensity ratio and [Ca2+]i. Dynamic changes of single-cell [Ca2+]i were measured either from one substrate-attached cell or from different adjacent cells in monolayer culture. Measurements of [Ca2+]i are taken successively in different subcellular locations (up to 10 measurement points). Each measurement cycle was repeated 60 times. To do so, an (X,Y) motorized stage coupled with a computer allowed us to store the (X,Y) positions of several chosen points for the laser radiation. Cells were monitored for about 10 min. After agonist stimulation. Upon stimulating with calcium ionophore, 4BrA23187 (1 (mu) M), [Ca2+]i increased immediately up to 10 fold from a resting value of 31 plus or minus 6 nM (n equals 36). Histamine (1 to 100 (mu) M) increased [Ca2+]i in a concentration dependent manner with levels of up to 88 nM and 140 nM for 1 (mu) M and 100 (mu) M concentration, respectively, followed by a smooth decay back to baseline. Removal of extracellular Ca2+ did not abolish the histamine-stimulation [Ca2+]i rise, suggesting that a part of Ca2+ mobilization comes from intracellular Ca2+ stores. These results show that the combined use of the UV microspectrofluorometry and Indo-1 is well adapted and straight forward for the measurement of rapid responses of substrate-attached cells during experiments of long

  12. Electron theory of fast and ultrafast dissipative magnetization dynamics.

    PubMed

    Fähnle, M; Illg, C

    2011-12-14

    For metallic magnets we review the experimental and electron-theoretical investigations of fast magnetization dynamics (on a timescale of ns to 100 ps) and of laser-pulse-induced ultrafast dynamics (few hundred fs). It is argued that for both situations the dominant contributions to the dissipative part of the dynamics arise from the excitation of electron-hole pairs and from the subsequent relaxation of these pairs by spin-dependent scattering processes, which transfer angular momentum to the lattice. By effective field theories (generalized breathing and bubbling Fermi-surface models) it is shown that the Gilbert equation of motion, which is often used to describe the fast dissipative magnetization dynamics, must be extended in several aspects. The basic assumptions of the Elliott-Yafet theory, which is often used to describe the ultrafast spin relaxation after laser-pulse irradiation, are discussed very critically. However, it is shown that for Ni this theory probably yields a value for the spin-relaxation time T(1) in good agreement with the experimental value. A relation between the quantity α characterizing the damping of the fast dynamics in simple situations and the time T(1) is derived. PMID:22089491

  13. Effect of β -amyloid Block of the Fast-Inactivating K+ Channel on Intracellular Ca2+ and Excitability in a Modeled Neuron

    NASA Astrophysics Data System (ADS)

    Good, Theresa A.; Murphy, Regina M.

    1996-12-01

    β -Amyloid peptide (Aβ ), one of the primary protein components of senile plaques found in Alzheimer disease, is believed to be toxic to neurons by a mechanism that may involve loss of intracellular calcium regulation. We have previously shown that Aβ blocks the fast-inactivating potassium (A) current. In this work, we show, through the use of a mathematical model, that the Aβ -mediated block of the A current could result in increased intracellular calcium levels and increased membrane excitability, both of which have been observed in vitro upon acute exposure to Aβ . Simulation results are compared with experimental data from the literature; the simulations quantitatively capture the observed concentration dependence of the neuronal response and the level of increase in intracellular calcium.

  14. Zinc-Permeable Ion Channels: Effects on Intracellular Zinc Dynamics and Potential Physiological/Pathophysiological Significance

    PubMed Central

    Inoue, Koichi; O'Bryant, Zaven; Xiong, Zhi-Gang

    2015-01-01

    Zinc (Zn2+) is one of the most important trace metals in the body. It is necessary for the normal function of a large number of proteins including enzymes and transcription factors. While extracellular fluid may contain up to micromolar Zn2+, intracellular Zn2+ concentration is generally maintained at a subnanomolar level; this steep gradient across the cell membrane is primarily attributable to Zn2+ extrusion by Zn2+ transporting systems. Interestingly, systematic investigation has revealed that activities, previously believed to be dependent on calcium (Ca2+), may be partially mediated by Zn2+. This is also supported by new findings that some Ca2+-permeable channels such as voltage-dependent calcium channels (VDCCs), N-methyl-D-aspartate receptors (NMDA), and amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPA-Rs) are also permeable to Zn2+. Thus, the importance of Zn2+ in physiological and pathophysiological processes is now more widely appreciated. In this review, we describe Zn2+-permeable membrane molecules, especially Zn2+-permeable ion channels, in intracellular Zn2+dynamics and Zn2+ mediated physiology/pathophysiology. PMID:25666796

  15. The dynamic Allan variance II: a fast computational algorithm.

    PubMed

    Galleani, Lorenzo

    2010-01-01

    The stability of an atomic clock can change with time due to several factors, such as temperature, humidity, radiations, aging, and sudden breakdowns. The dynamic Allan variance, or DAVAR, is a representation of the time-varying stability of an atomic clock, and it can be used to monitor the clock behavior. Unfortunately, the computational time of the DAVAR grows very quickly with the length of the analyzed time series. In this article, we present a fast algorithm for the computation of the DAVAR, and we also extend it to the case of missing data. Numerical simulations show that the fast algorithm dramatically reduces the computational time. The fast algorithm is useful when the analyzed time series is long, or when many clocks must be monitored, or when the computational power is low, as happens onboard satellites and space probes.

  16. Simulations of intracellular calcium release dynamics in response to a high-intensity, ultrashort electric pulse

    NASA Astrophysics Data System (ADS)

    Joshi, R. P.; Nguyen, A.; Sridhara, V.; Hu, Q.; Nuccitelli, R.; Beebe, S. J.; Kolb, J.; Schoenbach, K. H.

    2007-04-01

    Numerical simulations for electrically induced, intracellular calcium release from the endoplasmic reticulum are reported. A two-step model is used for self-consistency. Distributed electrical circuit representation coupled with the Smoluchowski equation yields the ER membrane nanoporation for calcium outflow based on a numerical simulation. This is combined with the continuum Li-Rinzel model and drift diffusion for calcium dynamics. Our results are shown to be in agreement with reported calcium release data. A modest increase (rough doubling) of the cellular calcium is predicted in the absence of extra-cellular calcium. In particular, the applied field of 15kV/cm with 60ns pulse duration makes for a strong comparison. No oscillations are predicted and the net recovery period of about 5min are both in agreement with published experimental results. A quantitative explanation for the lack of such oscillatory behavior, based on the density dependent calcium fluxes, is also provided.

  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. A new technique for fast dynamic focusing law computing

    NASA Astrophysics Data System (ADS)

    Fritsch, C.; Cruza, J. F.; Brizuela, J.; Camacho, J.; Moreno, J. M.

    2012-05-01

    Dynamic focusing requires computing the individual delays for every element and every focus in the image. This is an easy and relatively fast task if the inspected medium is homogeneous. Nevertheless, some difficulties arise in presence of interfaces (i.e, wedges, immersion, etc.): refraction effects require computing the Snell's law for every focus and element to find the fastest ray entry point in the interface. The process is easy but takes a long time. This work presents a new technique to compute the focusing delays for an equivalent virtual array that operates in the second medium only, thus avoiding any interface. It is nearly as fast as computing the focal laws in the homogeneous case and an order of magnitude faster than Snell's or Fermat's principle based methods. Furthermore, the technique is completely general and can be applied to any equipment having dynamic focusing capabilities. In fact, the technique is especially well suited for real-time focal law computing hardware.

  20. 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.

  1. 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.

  2. Fast Simulation on Flexible Multibody Dynamics Using Domain Decomposition Technique

    NASA Astrophysics Data System (ADS)

    Imanishi, Etsujiro; Nanjo, Takao; Hirooka, Eiko; Sugano, Naoki

    Recently, HILS (Hardware in the Loop Simulation) has been investigated in the field of the multibody dynamics (MBD). The fast calculation is necessary for the HILS system in order to require the real time simulation. This paper presents a fast simulation technique using the domain decomposition method. The domain decomposition method is widely used in the dynamic simulation for the mechanical system involving the hydraulic control system. This method is, however, not absolutely stable as the numerical integration. Fujikawa proposed a numerical stable solution scheme by introducing the iteration calculation. This paper applies the method to actual simulations of flexible multibody system in which the flexible linkage system and the hydraulic drive system are coupled with each other, and examines the speedup by parallel computing with the common memory in the calculation time. It is shown that using the present method in a multi-degrees-of freedom model can shorten the computing time. The present method is effective for the speedup in the calculation time by applying the dynamic simulation of the actual digging works on the hydraulic excavator.

  3. 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.

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

    PubMed

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

    2015-12-01

    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

  5. Analytic derivation of bacterial growth laws from a simple model of intracellular chemical dynamics.

    PubMed

    Pandey, Parth Pratim; Jain, Sanjay

    2016-09-01

    Experiments have found that the growth rate and certain other macroscopic properties of bacterial cells in steady-state cultures depend upon the medium in a surprisingly simple manner; these dependencies are referred to as 'growth laws'. Here we construct a dynamical model of interacting intracellular populations to understand some of the growth laws. The model has only three population variables: an amino acid pool, a pool of enzymes that transport an external nutrient and produce the amino acids, and ribosomes that catalyze their own and the enzymes' production from the amino acids. We assume that the cell allocates its resources between the enzyme sector and the ribosomal sector to maximize its growth rate. We show that the empirical growth laws follow from this assumption and derive analytic expressions for the phenomenological parameters in terms of the more basic model parameters. Interestingly, the maximization of the growth rate of the cell as a whole implies that the cell allocates resources to the enzyme and ribosomal sectors in inverse proportion to their respective 'efficiencies'. The work introduces a mathematical scheme in which the cellular growth rate can be explicitly determined and shows that two large parameters, the number of amino acid residues per enzyme and per ribosome, are useful for making approximations. PMID:27167220

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

    PubMed

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

    2015-12-01

    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.

  7. 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

  8. 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

  9. 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

  10. A dynamic intracellular distribution of Vangl2 accompanies cell polarization during zebrafish gastrulation

    PubMed Central

    Roszko, Isabelle; S. Sepich, Diane; Jessen, Jason R.; Chandrasekhar, Anand; Solnica-Krezel, Lilianna

    2015-01-01

    During vertebrate gastrulation, convergence and extension movements elongate embryonic tissues anteroposteriorly and narrow them mediolaterally. Planar cell polarity (PCP) signaling is essential for mediolateral cell elongation underlying these movements, but how this polarity arises is poorly understood. We analyzed the elongation, orientation and migration behaviors of lateral mesodermal cells undergoing convergence and extension movements in wild-type zebrafish embryos and mutants for the Wnt/PCP core component Vangl2 (Trilobite). We demonstrate that Vangl2 function is required at the time when cells transition to a highly elongated and mediolaterally aligned body. vangl2 mutant cells fail to undergo this transition and to migrate along a straight path with high net speed towards the dorsal midline. Instead, vangl2 mutant cells exhibit an anterior/animal pole bias in cell body alignment and movement direction, suggesting that PCP signaling promotes effective dorsal migration in part by suppressing anterior/animalward cell polarity and movement. Endogenous Vangl2 protein accumulates at the plasma membrane of mesenchymal converging cells at the time its function is required for mediolaterally polarized cell behavior. Heterochronic cell transplantations demonstrated that Vangl2 cell membrane accumulation is stage dependent and regulated by both intrinsic factors and an extracellular signal, which is distinct from PCP signaling or other gastrulation regulators, including BMP and Nodals. Moreover, mosaic expression of fusion proteins revealed enrichment of Vangl2 at the anterior cell edges of highly mediolaterally elongated cells. These results demonstrate that the dynamic Vangl2 intracellular distribution is coordinated with and necessary for the changes in convergence and extension cell behaviors during gastrulation. PMID:26062934

  11. 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

  12. 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

  13. Parvalbumin-immunoreactive, fast-spiking neurons in the medial septum/diagonal band complex of the rat: intracellular recordings in vitro.

    PubMed

    Morris, N P; Harris, S J; Henderson, Z

    1999-01-01

    The medial septum/diagonal band complex is composed predominantly of cholinergic and GABAergic neurons, and it projects to the hippocampal formation. A proportion of the GABAergic neurons contain parvalbumin, a calcium-binding protein that has previously been localized in fast-spiking, non-accommodating GABAergic neurons in the cerebral cortex and neostriatum. The aim of the present study was to determine whether parvalbumin is localized preferentially in a similar electrophysiological class of neuron in the medial septum/diagonal band complex. The study was carried out using in vitro intracellular recording, intracellular biocytin filling and parvalbumin immunocytochemistry. Three main classes of neurons were identified according to standard criteria: burst-firing, slow-firing and fast-firing neuronal populations. The fast-firing neurons were subdivided into two subpopulations based on whether or not they displayed accommodation. The fast-spiking, non-accommodating cells were furthermore found to be spontaneously active at resting potentials, and to possess action potentials of significantly (P < 0.05) shorter duration (half width: 0.61 +/- 0.12 ms) than those of the regular-spiking, accommodating neurons (1.0 +/- 0.34 ms). Of the neurons that were successfully filled with biocytin and processed for parvalbumin immunoreactivity, 82% of the fast-spiking, non-accommodating cells possessed parvalbumin immunoreactivity, while none of the regular-spiking, accommodating neurons were found to be immunoreactive for parvalbumin. The slow-firing neurons, shown previously to be cholinergic, did not stain for parvalbumin immunoreactivity, in agreement with studies showing parvalbumin to be localized solely in GABAergic neurons in the medial septum/diagonal band complex. In conclusion, these findings suggest the presence of a previously uncharacterized population of neurons in the medial septum/diagonal band complex that generate high-frequency, non-adaptive discharge. This

  14. Fast dynamics in glass-forming polymers revisited

    SciTech Connect

    Colmenero, J.; Arbe, A.; Mijangos, C.; Reinecke, H.

    1997-12-31

    The so called fast-dynamics of glass-forming systems as observed by time of flight (TOF) neutron scattering techniques is revisited. TOF-results corresponding to several glass-forming polymers with different chemical microstructure and glass-transition temperature are presented together with the theoretical framework proposed by the authors to interpret these results. The main conclusion is that the TOF-data can be explained in terms of quasiharmonic vibrations and the particular short time behavior of the segmental dynamics. The segmental dynamics display in the very short time range (t {approx} 2 ps) a crossover from a simple exponential behavior towards a non-exponential regime. The first exponential decay, which is controlled by C-C rotational barriers, can be understood as a trace of the behavior of the system in absence of the effects (correlations, cooperativity, memory effects {hor_ellipsis}) which characterize the dense supercooled liquid like state against the normal liquid state. The non-exponential regime at t > 2 ps corresponds to what is usually understood as {alpha} and {beta} relaxations. Some implications of these results are also discussed.

  15. 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.

  16. Dynamic Mode Decomposition of Fast Pressure Sensitive Paint Data.

    PubMed

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

    2016-06-11

    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.

  17. Fast-slow climate dynamics and peak global warming

    NASA Astrophysics Data System (ADS)

    Seshadri, Ashwin K.

    2016-06-01

    The dynamics of a linear two-box energy balance climate model is analyzed as a fast-slow system, where the atmosphere, land, and near-surface ocean taken together respond within few years to external forcing whereas the deep-ocean responds much more slowly. Solutions to this system are approximated by estimating the system's time-constants using a first-order expansion of the system's eigenvalue problem in a perturbation parameter, which is the ratio of heat capacities of upper and lower boxes. The solution naturally admits an interpretation in terms of a fast response that depends approximately on radiative forcing and a slow response depending on integrals of radiative forcing with respect to time. The slow response is inversely proportional to the "damping-timescale", the timescale with which deep-ocean warming influences global warming. Applications of approximate solutions are discussed: conditions for a warming peak, effects of an individual pulse emission of carbon dioxide (CO2 ), and metrics for estimating and comparing contributions of different climate forcers to maximum global warming.

  18. Dynamic Mode Decomposition of Fast Pressure Sensitive Paint Data.

    PubMed

    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

  19. 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

  20. A fast-marching like algorithm for geometrical shock dynamics

    NASA Astrophysics Data System (ADS)

    Noumir, Y.; Le Guilcher, A.; Lardjane, N.; Monneau, R.; Sarrazin, A.

    2015-03-01

    We develop a new algorithm for the computation of the Geometrical Shock Dynamics (GSD) model. The method relies on the fast-marching paradigm and enables the discrete evaluation of the first arrival time of a shock wave and its local velocity on a Cartesian grid. The proposed algorithm is based on a first order upwind finite difference scheme and reduces to a local nonlinear system of two equations solved by an iterative procedure. Reference solutions are built for a smooth radial configuration and for the 2D Riemann problem. The link between the GSD model and p-systems is given. Numerical experiments demonstrate the efficiency of the scheme and its ability to handle singularities.

  1. 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.

  2. Properties and applications of fast rotors in dynamical optics (abstract)

    SciTech Connect

    Csonka, P. L.

    1989-07-01

    The term ''dynamical optics'' is defined as a set of optical elements at least one of which is nonstationary as seen from the laboratory. Present technology allows the construction of fast rotating mirrors as components in dynamical optical systems. Calculations show that such systems can be used to achieve subpicosecond x-ray pulses and extremely high instantaneous intensities, and, alternatively they can be utilized to saturate the transverse coherence of x-ray beams thereby making possible to perform certain interference experiments. Some properties and additional applications of fast rotating mirrors are discussed: (1) The focusing properties of rotating mirrors can differ significantly from those of stationary reflectors, even though the mirrors are, of course, nonrelativistic. A small (diameter /lt/1 mm) plane mirror when rotating can have a focal length /ital f//sub /ital m// down to a few meters. By changing the speed of rotation, the focal length can be altered continuously from its minimum value, /ital f//sub /ital m//, through infinity (when the mirror is at rest) to /minus//ital f//sub /ital m// (when it's rotation is reversed). Thus, mirrors can be constructed which can be made to both focus and defocus with continuously and accurately variable focal length. (2) Rotating mirrors will induce a frequency change /Delta//omega/ in the reflected beam, allowing one in principle to tune across resonance lines, and also ''active monochromatization'' of x-rays, i.e., increasing the spectral intensity in a selected range, while decreasing it outside that range, all this without any change in the total photon beam intensity. This option is of interest when the total photon intensity cannot be increased beyond a certain limit, high resolution monochromatization is available, and large spectral density is called for in a chosen frequency range.

  3. 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. PMID:26561642

  4. 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.

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

    PubMed

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

    2014-05-21

    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.

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

    PubMed Central

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

    2014-01-01

    Slow-twitch (type 1) skeletal muscle fibers have markedly greater mitochondrial content than fast-twitch (type 2) fibers. Accordingly, we sought to determine whether the dielectric properties of these two fiber types differed, consistent with their distinct intracellular morphologies. The longitudinal and transverse dielectric spectrum of the ex vivo rat soleus (a predominantly type 1 muscle) and the superficial layers of rat gastrocnemius (predominantly type 2) (n = 15) were measured in the 1 kHz–10 MHz frequency range and modeled to a resistivity Cole–Cole function. Major differences were especially apparent in the dielectric spectrum in the 1 to 10 MHz range. Specifically, the gastrocnemius demonstrated a well-defined, higher center frequency than the soleus muscle, whereas the soleus muscle showed a greater difference in the modeled zero and infinite resistivities than the gastrocnemius. These findings are consistent with the fact that soleus tissue has larger and more numerous mitochondria than gastrocnemius. Evaluation of tissue at high frequency could provide a novel approach for assessing intracellular structure in health and disease. PMID:24743385

  7. 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.

  8. Fast passage dynamic nuclear polarization on rotating solids

    NASA Astrophysics Data System (ADS)

    Mentink-Vigier, Frederic; Akbey, Ümit; Hovav, Yonatan; Vega, Shimon; Oschkinat, Hartmut; Feintuch, Akiva

    2012-11-01

    Magic Angle Spinning (MAS) Dynamic Nuclear Polarization (DNP) has proven to be a very powerful way to improve the signal to noise ratio of NMR experiments on solids. The experiments have in general been interpreted considering the Solid-Effect (SE) and Cross-Effect (CE) DNP mechanisms while ignoring the influence of sample spinning. In this paper, we show experimental data of MAS-DNP enhancements of 1H and 13C in proline and SH3 protein in glass forming water/glycerol solvent containing TOTAPOL. We also introduce a theoretical model that aims at explaining how the nuclear polarization is built in MAS-DNP experiments. By using Liouville space based simulations to include relaxation on two simple spin models, {electron-nucleus} and {electron-electron-nucleus}, we explain how the basic MAS-SE-DNP and MAS-CE-DNP processes work. The importance of fast energy passages and short level anti-crossing is emphasized and the differences between static DNP and MAS-DNP is explained. During a single rotor cycle the enhancement in the {electron-electron-nucleus} system arises from MAS-CE-DNP involving at least three kinds of two-level fast passages: an electron-electron dipolar anti-crossing, a single quantum electron MW encounter and an anti-crossing at the CE condition inducing nuclear polarization in- or decrements. Numerical, powder-averaged, simulations were performed in order to check the influence of the experimental parameters on the enhancement efficiencies. In particular we show that the spinning frequency dependence of the theoretical MAS-CE-DNP enhancement compares favorably with the experimental 1H and 13C MAS-DNP enhancements of proline and SH3.

  9. Fast passage dynamic nuclear polarization on rotating solids.

    PubMed

    Mentink-Vigier, Frederic; Akbey, Umit; Hovav, Yonatan; Vega, Shimon; Oschkinat, Hartmut; Feintuch, Akiva

    2012-11-01

    Magic Angle Spinning (MAS) Dynamic Nuclear Polarization (DNP) has proven to be a very powerful way to improve the signal to noise ratio of NMR experiments on solids. The experiments have in general been interpreted considering the Solid-Effect (SE) and Cross-Effect (CE) DNP mechanisms while ignoring the influence of sample spinning. In this paper, we show experimental data of MAS-DNP enhancements of (1)H and (13)C in proline and SH3 protein in glass forming water/glycerol solvent containing TOTAPOL. We also introduce a theoretical model that aims at explaining how the nuclear polarization is built in MAS-DNP experiments. By using Liouville space based simulations to include relaxation on two simple spin models, {electron-nucleus} and {electron-electron-nucleus}, we explain how the basic MAS-SE-DNP and MAS-CE-DNP processes work. The importance of fast energy passages and short level anti-crossing is emphasized and the differences between static DNP and MAS-DNP is explained. During a single rotor cycle the enhancement in the {electron-electron-nucleus} system arises from MAS-CE-DNP involving at least three kinds of two-level fast passages: an electron-electron dipolar anti-crossing, a single quantum electron MW encounter and an anti-crossing at the CE condition inducing nuclear polarization in- or decrements. Numerical, powder-averaged, simulations were performed in order to check the influence of the experimental parameters on the enhancement efficiencies. In particular we show that the spinning frequency dependence of the theoretical MAS-CE-DNP enhancement compares favorably with the experimental (1)H and (13)C MAS-DNP enhancements of proline and SH3.

  10. Dynamics of the antibody-T.cruzi competition during Chagas infection: Prognostic relevance of intracellular replication

    NASA Astrophysics Data System (ADS)

    Sibona, G. J.; Condat, C. A.; Isasi, S. Cossy

    2005-02-01

    A recently proposed model for the competitive parasite-antibody interactions in Chagas disease is extended by separately describing the parasitic intracellular and extracellular phases. The model solutions faithfully reproduce available population data and yield predictions for parasite-induced cardiac cell damage.

  11. Optimization of replica exchange molecular dynamics by fast mimicking.

    PubMed

    Hritz, Jozef; Oostenbrink, Chris

    2007-11-28

    We present an approach to mimic replica exchange molecular dynamics simulations (REMD) on a microsecond time scale within a few minutes rather than the years, which would be required for real REMD. The speed of mimicked REMD makes it a useful tool for "testing" the efficiency of different settings for REMD and then to select those settings, that give the highest efficiency. We present an optimization approach with the example of Hamiltonian REMD using soft-core interactions on two model systems, GTP and 8-Br-GTP. The optimization process using REMD mimicking is very fast. Optimization of Hamiltonian-REMD settings of GTP in explicit water took us less than one week. In our study we focus not only on finding the optimal distances between neighboring replicas, but also on finding the proper placement of the highest level of softness. In addition we suggest different REMD simulation settings at this softness level. We allow several replicas to be simulated at the same Hamiltonian simultaneously and reduce the frequency of switching attempts between them. This approach allows for more efficient conversions from one stable conformation to the other.

  12. Intracellular and extracellular pH dynamics in the human placenta from diabetes mellitus.

    PubMed

    Araos, Joaquín; Silva, Luis; Salsoso, Rocío; Sáez, Tamara; Barros, Eric; Toledo, Fernando; Gutiérrez, Jaime; Pardo, Fabián; Leiva, Andrea; Sanhueza, Carlos; Sobrevia, Luis

    2016-07-01

    The placenta is a vital organ whose function in diseases of pregnancy is altered, resulting in an abnormal supply of nutrients to the foetus. The lack of placental vasculature homeostasis regulation causes endothelial dysfunction and altered vascular reactivity. The proper distribution of acid- (protons (H(+))) and base-equivalents through the placenta is essential to achieve physiological homeostasis. Several membrane transport mechanisms that control H(+) distribution between the extracellular and intracellular spaces are expressed in the human placenta vascular endothelium and syncytiotrophoblast, including sodium (Na(+))/H(+) exchangers (NHEs). One member of the NHEs family is NHE isoform 1 (NHE1), whose activity results in an alkaline intracellular pH (high intracellular pH (pHi)) and an acidic extracellular pH (pHo). Increased NHE1 expression, maximal transport activity, and turnover are reported in human syncytiotrophoblasts and lymphocytes from patients with diabetes mellitus type I (DMT1), and a positive correlation between NHEs activity and plasma factors, such as that between thrombin and platelet factor 3, has been reported in diabetes mellitus type II (DMT2). However, gestational diabetes mellitus (GDM) could result in a higher sensitivity of the human placenta to acidic pHo. We summarized the findings on pHi and pHo modulation in the human placenta with an emphasis on pregnancies in which the mother diagnosed with diabetes mellitus. A potential role of NHEs, particularly NHE1, is proposed regarding placental dysfunction in DMT1, DMT2, and GDM.

  13. Mechanisms of intracellular defense and activity of free radical oxidation in rat myocardium in the dynamics of chronic fluorine intoxication.

    PubMed

    Zhukova, A G; Alekhina, D A; Sazontova, T G; Prokop'ev, Yu A; Gorokhova, L G; Stryapko, N V; Mikhailova, N N

    2013-12-01

    The mechanisms of intracellular defense and activity of free radical oxidation in the myocardium were studied in the dynamics of chronic fluorine intoxication. At the early stages of fluorine intoxication (day 3-week 3), the concentrations of defense proteins HIF-1α, HSC73, and HOx-2 and activity of the main metabolic enzymes increased, which promoted maintenance of cardiomyocyte structure and function at the normal physiological level. At late stages of fluorine intoxication (weeks 6 and 9), metabolic changes in the myocardium attest to high strain of the adaptive mechanisms.

  14. 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.

  15. Measurement of shear stress-mediated intracellular calcium dynamics in human dermal lymphatic endothelial cells

    PubMed Central

    Jafarnejad, M.; Cromer, W. E.; Kaunas, R. R.; Zhang, S. L.; Zawieja, D. C.

    2015-01-01

    The shear stress applied to lymphatic endothelial cells (LEC) by lymph flow changes dramatically under normal conditions as well as in response to disease conditions and immune reactions. In general, LEC are known to regulate the contraction frequency and strength of lymphatic pumping in response to shear stress. Intracellular calcium concentration ([Ca2+]i) is an important factor that regulates lymphatic contraction characteristics. In this study, we measured changes in the [Ca2+]i under different shear stress levels and determined the source of this calcium signal. Briefly, human dermal LEC were cultured in custom-made microchannels for 3 days before loading with 2 µM fura-2 AM, a ratiometric calcium dye to measure [Ca2+]i. Step changes in shear stress resulted in a rapid increase in [Ca2+]i followed by a gradual return to the basal level and sometimes below the initial baseline (45.2 ± 2.2 nM). The [Ca2+]i reached a peak at 126.2 ± 5.6 nM for 10 dyn/cm2 stimulus, whereas the peak was only 71.8 ± 5.4 nM for 1 dyn/cm2 stimulus, indicating that the calcium signal depends on the magnitude of shear stress. Removal of the extracellular calcium from the buffer or pharmocological blockade of calcium release-activated calcium (CRAC) channels significantly reduced the peak [Ca2+]i, demonstrating a role of extracellular calcium entry. Inhibition of endoplasmic reticulum (ER) calcium pumps showed the importance of intracellular calcium stores in the initiation of this signal. In conclusion, we demonstrated that the shear-mediated calcium signal is dependent on the magnitude of the shear and involves ER store calcium release and extracellular calcium entry. PMID:25617358

  16. The Effects of Diuretics on Intracellular Ca2+ Dynamics of Arteriole Smooth Muscles as Revealed by Laser Confocal Microscopy

    PubMed Central

    Tamagawa, Yasunori; Saino, Tomoyuki; Matsuura, Makoto; Satoh, Yoh-ichi

    2009-01-01

    The regulation of cytosolic Ca2+ homeostasis is essential for cells, including vascular smooth muscle cells. Arterial tone, which underlies the maintenance of peripheral resistance in the circulation, is a major contributor to the control of blood pressure. Diuretics may regulate intracellular Ca2+ concentration ([Ca2+]i) and have an effect on vascular tone. In order to investigate the influence of diuretics on peripheral resistance in circulation, we investigated the alteration of [Ca2+]i in testicular arterioles with respect to several categories of diuretics using real-time confocal laser scanning microscopy. In this study, hydrochlorothiazide (100 µM) and furosemide (100 µM) had no effect on the [Ca2+]i dynamics. However, when spironolactone (300 µM) was applied, the [Ca2+]i of smooth muscles increased. The response was considerably inhibited under either extracellular Ca2+-free conditions, the presence of Gd3+, or with a treatment of diltiazem. After the thapsigargin-induced depletion of internal Ca2+ store, the spironolactone-induced [Ca2+]i dynamics was slightly inhibited. Therefore, the spironolactone-induced dynamics of [Ca2+]i can be caused by either a Ca2+ influx from extracellular fluid or Ca2+ mobilization from internal Ca2+ store, with the former being dominant. As tetraethylammonium, an inhibitor of the K+ channel, slightly inhibited the spironolactone-induced [Ca2+]i dynamics, the K+ channel might play a minor role in those dynamics. Tetrodotoxin, a neurotoxic Na+ channel blocker, had no effect, therefore the spironolactone-induced dynamics is a direct effect to smooth muscles, rather than an indirect effect via vessel nerves. PMID:19759873

  17. Comment on ``Fast dynamics of glass-forming glycerol''

    NASA Astrophysics Data System (ADS)

    Ngai, K. L.; Roland, C. M.

    1997-02-01

    The coupling model predicts the existence of a prominent fast α process at times <2 ps in fragile glass-forming liquids such as polymers. A further prediction is that this process will be only weakly apparent in intermediate and strong liquids such as glycerol. In light of these predictions, we have reexamined the neutron scattering data of glycerol published by Wuttke, Petry, Coddens, and Fujara (WPCF) [Phys. Rev. E 52, 4026 (1995)], leading to the conclusion that the fast α process is indeed quite weak therein. Thus, the coupling model predictions are fully consistent with the glycerol data, notwithstanding WPCF's statement to the contrary.

  18. 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.

  19. Compression dynamics of an indirect drive fast ignition target

    SciTech Connect

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

    2002-11-12

    In an x-ray driven reentrant cone fast ignition target the x-ray spectrum contains a high energy component that cause preheating of the reentrant cone and mixing of its gold into the collapsing shell. Direct laser drive might avoid this problem.

  20. Suppression of dynamics and frequency synchronization in coupled slow and fast dynamical systems

    NASA Astrophysics Data System (ADS)

    Gupta, Kajari; Ambika, G.

    2016-06-01

    We present our study on the emergent states of two interacting nonlinear systems with differing dynamical time scales. We find that the inability of the interacting systems to fall in step leads to difference in phase as well as change in amplitude. If the mismatch is small, the systems settle to a frequency synchronized state with constant phase difference. But as mismatch in time scale increases, the systems have to compromise to a state of no oscillations. We illustrate this for standard nonlinear systems and identify the regions of quenched dynamics in the parameter plane. The transition curves to this state are studied analytically and confirmed by direct numerical simulations. As an important special case, we revisit the well-known model of coupled ocean-atmosphere system used in climate studies for the interactive dynamics of a fast oscillating atmosphere and slowly changing ocean. Our study in this context indicates occurrence of multi stable periodic states and steady states of convection coexisting in the system, with a complex basin structure.

  1. 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.

  2. 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).

  3. Wide dynamic range neutron flux monitor having fast time response for the Large Helical Device.

    PubMed

    Isobe, M; Ogawa, K; Miyake, H; Hayashi, H; Kobuchi, T; Nakano, Y; Watanabe, K; Uritani, A; Misawa, T; Nishitani, T; Tomitaka, M; Kumagai, T; Mashiyama, Y; Ito, D; Kono, S; Yamauchi, M; Takeiri, Y

    2014-11-01

    A fast time response, wide dynamic range neutron flux monitor has been developed toward the LHD deuterium operation by using leading-edge signal processing technologies providing maximum counting rate up to ∼5 × 10(9) counts/s. Because a maximum total neutron emission rate over 1 × 10(16) n/s is predicted in neutral beam-heated LHD plasmas, fast response and wide dynamic range capabilities of the system are essential. Preliminary tests have demonstrated successful performance as a wide dynamic range monitor along the design.

  4. Wide dynamic range neutron flux monitor having fast time response for the Large Helical Device

    SciTech Connect

    Isobe, M. Takeiri, Y.; Ogawa, K.; Miyake, H.; Hayashi, H.; Kobuchi, T.; Nakano, Y.; Watanabe, K.; Uritani, A.; Misawa, T.; Nishitani, T.; Tomitaka, M.; Kumagai, T.; Mashiyama, Y.; Ito, D.; Kono, S.; Yamauchi, M.

    2014-11-15

    A fast time response, wide dynamic range neutron flux monitor has been developed toward the LHD deuterium operation by using leading-edge signal processing technologies providing maximum counting rate up to ∼5 × 10{sup 9} counts/s. Because a maximum total neutron emission rate over 1 × 10{sup 16} n/s is predicted in neutral beam-heated LHD plasmas, fast response and wide dynamic range capabilities of the system are essential. Preliminary tests have demonstrated successful performance as a wide dynamic range monitor along the design.

  5. Wide dynamic range neutron flux monitor having fast time response for the Large Helical Devicea)

    NASA Astrophysics Data System (ADS)

    Isobe, M.; Ogawa, K.; Miyake, H.; Hayashi, H.; Kobuchi, T.; Nakano, Y.; Watanabe, K.; Uritani, A.; Misawa, T.; Nishitani, T.; Tomitaka, M.; Kumagai, T.; Mashiyama, Y.; Ito, D.; Kono, S.; Yamauchi, M.; Takeiri, Y.

    2014-11-01

    A fast time response, wide dynamic range neutron flux monitor has been developed toward the LHD deuterium operation by using leading-edge signal processing technologies providing maximum counting rate up to ˜5 × 109 counts/s. Because a maximum total neutron emission rate over 1 × 1016 n/s is predicted in neutral beam-heated LHD plasmas, fast response and wide dynamic range capabilities of the system are essential. Preliminary tests have demonstrated successful performance as a wide dynamic range monitor along the design.

  6. 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

  7. Mathematical modeling of the intracellular protein dynamics: the importance of active transport along microtubules.

    PubMed

    Szymańska, Zuzanna; Parisot, Martin; Lachowicz, Mirosław

    2014-12-21

    In this paper we propose a mathematical model of protein and mRNA transport inside a cell. The spatio-temporal model takes into account the active transport along microtubules in the cytoplasm as well as diffusion and is able to reproduce the oscillatory changes in protein concentration observed in many experimental data. In the model the protein and the mRNA interact with each other that allows us to classify the model as a simple gene regulatory network. The proposed model is generic and may be adapted to specific signaling pathways. On the basis of numerical simulations, we formulate a new hypothesis that the oscillatory dynamics is allowed by the mRNA active transport along microtubules from the nucleus to distant locations.

  8. 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.

  9. 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.

  10. 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.

  11. Dynamics of a plant RNA virus intracellular accumulation: stamping machine vs. geometric replication.

    PubMed

    Martínez, Fernando; Sardanyés, Josep; Elena, Santiago F; Daròs, José-Antonio

    2011-07-01

    The tremendous evolutionary potential of RNA viruses allows them to thrive despite host defense mechanisms and endows them with properties such as emergence, host switching, and virulence. The frequency of mutant viruses after an infectious process results from the interplay between the error rate of the viral replicase, from purifying mechanisms acting after transcription on aberrant RNAs, and from the amplification dynamics of virus RNA positive (+) and negative (-) strands. Two extreme scenarios describing viral RNA amplification are the geometric growth, in which each RNA strand serves as template for the synthesis of complementary strands with the same efficiency, and the stamping machine, where a strand is reiteratively used as template to synthesize multiple copies of the complementary. The resulting mutation frequencies are completely different, being geometric growth largely more mutagenic than stamping machine. In this work we evaluate the contribution of geometric growth and stamping machine to the overall genome amplification of the plant (+)-strand RNA virus turnip mosaic virus (TuMV). By means of transfection experiments of Nicotiana benthamiana protoplasts with a TuMV cDNA infectious clone and by using strand-specific quantitative real-time PCR, we determined the amplification dynamics of viral (+) and (-) RNA during a single-cell infectious process. A mathematical model describing the amplification of each viral strand was fitted to the data. Analyses of the model parameters showed that TuMV (+) and (-) RNA amplification occurs through a mixed strategy with ∼93% of genomes produced via stamping machine and only ∼7% resulting from geometric growth. PMID:21515574

  12. 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

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

    PubMed

    Goode, Angela E; 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; Porter, Alexandra E

    2015-11-01

    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 MWNTs, 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 h 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 h. 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

  14. 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.

  15. 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).

  16. Intracellular dialysis disrupts Zn2+ dynamics and enables selective detection of Zn2+ influx in brain slice preparations.

    PubMed

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

    2013-06-01

    We examined the impact of intracellular dialysis on fluorescence detection of neuronal intracellular Zn(2+) accumulation. Comparison between two dialysis conditions (standard; 20 min, brief; 2 min) by standard whole-cell clamp revealed a high vulnerability of intracellular Zn(2+) 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 Zn(2+) pools was 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 Zn(2+) 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 Zn(2+) (ZnT3-KO). In contrast, under brief dialysis conditions, intracellular Zn(2+) transients were very similar in WT and ZnT3-KO preparations. This suggests that both intracellular release and transmembrane flux can contribute to intracellular Zn(2+) accumulation after synaptic stimulation. These results demonstrate significant confounds and potential use of intracellular dialysis to investigate intracellular Zn(2+) accumulation mechanisms. PMID:23517525

  17. Spatial Heat Maps from Fast Information Matching of Fast and Slow Degrees of Freedom: Application to Molecular Dynamics Simulations.

    PubMed

    Kovacs, Julio A; Wriggers, Willy

    2016-08-25

    We introduce a fast information matching (FIM) method for transforming time domain data into spatial images through handshaking between fast and slow degrees of freedom. The analytics takes advantage of the detailed time series available from biomolecular computer simulations, and it yields spatial heat maps that can be visualized on 3D molecular structures or in the form of interaction networks. The speed of our efficient mutual information solver is on the order of a basic Pearson cross-correlation calculation. We demonstrate that the FIM method is superior to linear cross-correlation for the detection of nonlinear dependence in challenging situations where measures for the global dynamics (the "activity") diverge. The analytics is applied to the detection of hinge-bending hot spots and to the prediction of pairwise contacts between residues that are relevant for the global activity exhibited by the molecular dynamics (MD) trajectories. Application examples from various MD laboratories include the millisecond bovine pancreatic trypsin inhibitor (BPTI) trajectory using canonical MD, a Gaussian accelerated MD folding trajectory of chignolin, and the heat-induced unfolding of engrailed homeodomain (EnHD). The FIM implementation will be freely disseminated with our open-source package, TimeScapes.

  18. Fast molecular tracking maps nanoscale dynamics of plasma membrane lipids

    PubMed Central

    Sahl, Steffen J.; Leutenegger, Marcel; Hilbert, Michael; Hell, Stefan W.; Eggeling, Christian

    2010-01-01

    We describe an optical method capable of tracking a single fluorescent molecule with a flexible choice of high spatial accuracy (∼10–20 nm standard deviation or ∼20–40 nm full-width-at-half-maximum) and temporal resolution (< 1 ms). The fluorescence signal during individual passages of fluorescent molecules through a spot of excitation light allows the sequential localization and thus spatio-temporal tracking of the molecule if its fluorescence is collected on at least three separate point detectors arranged in close proximity. We show two-dimensional trajectories of individual, small organic dye labeled lipids diffusing in the plasma membrane of living cells and directly observe transient events of trapping on < 20 nm spatial scales. The trapping is cholesterol-assisted and much more pronounced for a sphingo- than for a phosphoglycero-lipid, with average trapping times of ∼15 ms and < 4 ms, respectively. The results support previous STED nanoscopy measurements and suggest that, at least for nontreated cells, the transient interaction of a single lipid is confined to macromolecular dimensions. Our experimental approach demonstrates that fast molecular movements can be tracked with minimal invasion, which can reveal new important details of cellular nano-organization. PMID:20351247

  19. 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.

  20. 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

  1. Fast and Efficient Dynamic WDM Semiconductor Optical Amplifier Model

    NASA Astrophysics Data System (ADS)

    Mathlouthi, Walid; Lemieux, Pascal; Salsi, Massimiliano; Vannucci, Armando; Bononi, Alberto; Rusch, Leslie A.

    2006-11-01

    A novel state-variable model for semiconductor optical amplifiers (SOAs) that is amenable to block diagram implementation of wavelength division multiplexed (WDM) signals and fast execution times is presented. The novel model is called the reservoir model, in analogy with similar block-oriented models for Raman and erbium-doped fiber amplifiers (EDFAs). A procedure is proposed to extract the needed reservoir model parameters from the parameters of a detailed and accurate space-resolved SOA model due to Connelly, which was extended to cope with the time-resolved gain transient analysis. Several variations of the reservoir model are considered with increasing complexity, which allow the accurate inclusion of scattering losses and gain saturation induced by amplified spontaneous emission. It is shown that at comparable accuracy, the reservoir model can be 20 times faster than the Connelly model in single-channel operation; much more significant time savings are expected for WDM operation. The model neglects intraband SOA phenomena and is thus limited to modulation rates per channel not exceeding 10 Gb/s. The SOA reservoir model provides a unique tool with reasonably short computation times for a reliable analysis of gain transients in WDM optical networks with complex topologies.

  2. Fast Auroral Snapshot performance using a multi-body dynamic simulation

    NASA Technical Reports Server (NTRS)

    Zimbelman, Darrell; Walker, Mary

    1993-01-01

    This paper examines the complex dynamic interaction between two 2.6 m long stacer booms, four 30 m long flexible wire booms and the attitude control system of the Fast Auroral SnapshoT (FAST) spacecraft. The FAST vehicle will nominally operate as a negative orbit spinner, positioned in a 83 deg inclination, 350 x 4200 km orbit. For this study, a three-axis, non-linear, seven body dynamic simulation is developed using the TREETOPS software package. The significance of this approach is the ability to model each component of the FAST spacecraft as an individual member and connect them together in order to better understand the dynamic coupling between structures and the control system. Both the wire and stacer booms are modeled as separate bodies attached to a rigid central body. The wire booms are oriented perpendicular to the spin axis at right angles relative to each other, whereas the stacer booms are aligned with the spin axis. The analysis consists of a comparison between the simulated in-plane and out-of-plane boom motions with theoretically derived frequencies, and an examination of the dynamic coupling between the control system and boom oscillations. Results show that boom oscillations of up to 0.36 deg are acceptable in order to meet the performance requirements. The dynamic motion is well behaved when the precession coil is operating, however, activation of the spin coil produces an erratic trend in the spin rate which approaches the spin rate requirement.

  3. 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

  4. 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.

  5. 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. PMID:26074953

  6. Dynamics of pre-ionized fast capillary discharge

    NASA Astrophysics Data System (ADS)

    Hübner, J.; Vrba, P.; Straus, J.; Jancarek, A.; Nevrkla, M.

    2014-05-01

    The goal of this work is to determine the best conditions for pre-ionization of the nitrogen filled capillary plasma column applying an external exponentially damped or high-frequency alternating current. As we supposed, optimal pre-ionization conditions are achieved when the plasma is quiescent, motionless and isothermal, near the local thermodynamical equilibrium. At the time of optimal conditions for the pre-ionization plasma column, the main pulse is applied. This approach enables us to estimate the influence of such prepared plasma on the value of emitted energy during the main current pulse. For modeling of plasma during the pre-pulse and main pulse, the magneto-hydro-dynamics (MHD) NPINCH code [1] and the radiative-MHD Z* code [2] were used. The computer results are used for further improvement of x-ray-ultraviolet-capillary sources designed in IPP ASCR and CTU FNSPE laboratories in Prague.

  7. 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.

  8. Fast infrared spectroscopy of protein dynamics: advancing sensitivity and selectivity.

    PubMed

    Koziol, Klemens L; Johnson, Philip J M; Stucki-Buchli, Brigitte; Waldauer, Steven A; Hamm, Peter

    2015-10-01

    2D-IR spectroscopy has matured to a powerful technique to study the structure and dynamics of peptides, but its extension to larger proteins is still in its infancy, the major limitations being sensitivity and selectivity. Site-selective information requires measuring single vibrational probes at sub-millimolar concentrations where most proteins are still stable, which is a severe challenge for conventional (FT)IR spectroscopy. Besides its ultrafast time-resolution, a so far largely underappreciated potential of 2D-IR spectroscopy lies in its sensitivity gain. The present paper sets the goals and outlines strategies how to use that sensitivity gain together with properly designed vibrational labels to make IR spectroscopy a versatile tool to study a wide class of proteins.

  9. 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

  10. 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

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

    PubMed

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

    2015-07-01

    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. (13)C-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 (3)H-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

  12. 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

  13. 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.

  14. FAST TRACK COMMUNICATION: Local Hawking temperature for dynamical black holes

    NASA Astrophysics Data System (ADS)

    Hayward, S. A.; Di Criscienzo, R.; Nadalini, M.; Vanzo, L.; Zerbini, S.

    2009-03-01

    A local Hawking temperature is derived for any future outer trapping horizon in spherical symmetry, using a Hamilton Jacobi variant of the Parikh Wilczek tunneling method. It is given by a dynamical surface gravity as defined geometrically. The operational meaning of the temperature is that Kodama observers just outside the horizon measure an invariantly redshifted temperature, diverging at the horizon itself. In static, asymptotically flat cases, the Hawking temperature as usually defined by the Killing vector agrees in standard cases, but generally differs by a relative redshift factor between the horizon and infinity, this being the temperature measured by static observers at infinity. Likewise, the geometrical surface gravity reduces to the Newtonian surface gravity in the Newtonian limit, while the Killing definition instead reflects measurements at infinity. This may resolve a long-standing puzzle concerning the Hawking temperature for the extremal limit of the charged stringy black hole, namely that it is the local temperature which vanishes. In general, this confirms the quasi-stationary picture of black-hole evaporation in early stages. However, the geometrical surface gravity is generally not the surface gravity of a static black hole with the same parameters.

  15. 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

    2009-09-01

    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.

  16. 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.

  17. Dynamical tunneling versus fast diffusion for a non-convex Hamiltonian

    NASA Astrophysics Data System (ADS)

    Pittman, S. M.; Tannenbaum, E.; Heller, E. J.

    2016-08-01

    This paper attempts to resolve the issue of the nature of the 0.01-0.1 cm-1 peak splittings observed in high-resolution IR spectra of polyatomic molecules. One hypothesis is that these splittings are caused by dynamical tunneling, a quantum-mechanical phenomenon whereby energy flows between two disconnected regions of phase-space across dynamical barriers. However, a competing classical mechanism for energy flow is Arnol'd diffusion, which connects different regions of phase-space by a resonance network known as the Arnol'd web. The speed of diffusion is bounded by the Nekhoroshev theorem, which guarantees stability on exponentially long time scales if the Hamiltonian is steep. Here we consider a non-convex Hamiltonian that contains the characteristics of a molecular Hamiltonian, but does not satisfy the Nekhoroshev theorem. The diffusion along the Arnol'd web is expected to be fast for a non-convex Hamiltonian. While fast diffusion is an unlikely competitor for longtime energy flow in molecules, we show how dynamical tunneling dominates compared to fast diffusion in the nearly integrable regime for a non-convex Hamiltonian, as well as present a new kind of dynamical tunneling.

  18. Coordinated Action of Fast and Slow Reserves for Optimal Sequential and Dynamic Emergency Reserve Activation

    NASA Astrophysics Data System (ADS)

    Salkuti, Surender Reddy; Bijwe, P. R.; Abhyankar, A. R.

    2016-04-01

    This paper proposes an optimal dynamic reserve activation plan after the occurrence of an emergency situation (generator/transmission line outage, load increase or both). An optimal plan is developed to handle the emergency situation, using coordinated action of fast and slow reserves, for secure operation with minimum overall cost. This paper considers the reserves supplied by generators (spinning reserves) and loads (demand-side reserves). The optimal backing down of costly/fast reserves and bringing up of slow reserves in each sub-interval in an integrated manner is proposed. The simulation studies are performed on IEEE 30, 57 and 300 bus test systems to demonstrate the advantage of proposed integrated/dynamic reserve activation plan over the conventional/sequential approach.

  19. An efficient scheme for sampling fast dynamics at a low average data acquisition rate.

    PubMed

    Philippe, A; Aime, S; Roger, V; Jelinek, R; Prévot, G; Berthier, L; Cipelletti, L

    2016-02-24

    We introduce a temporal scheme for data sampling, based on a variable delay between two successive data acquisitions. The scheme is designed so as to reduce the average data flow rate, while still retaining the information on the data evolution on fast time scales. The practical implementation of the scheme is discussed and demonstrated in light scattering and microscopy experiments that probe the dynamics of colloidal suspensions using CMOS or CCD cameras as detectors.

  20. 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; 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-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

  1. 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

  2. Real-Time Monitoring the Spatiotemporal Dynamics of Intracellular cGMP in Vascular Smooth Muscle Cells

    PubMed Central

    Held, Kara F.; Dostmann, Wolfgang R.

    2016-01-01

    Real-time and noninvasive imaging of intracellular second messengers in mammalian cells, while preserving their in vivo phenotype, requires biosensors of exquisite constitution. Here we provide the methodology for utilizing the single wavelength cGMP-biosensor δ-FlincG in aortic vascular smooth muscle cells. PMID:23709030

  3. Imaging Ultra-fast Molecular Dynamics in Free Electron Laser Field

    NASA Astrophysics Data System (ADS)

    Zhang, Y. Z.; Jiang, Y. H.

    The free electron laser (FEL) provides the coherent, brilliant and ultrashort light pulse in short wavelength (extreme ultraviolet and X-ray) regimes, opening up possibilities to study ultra-fast molecular dynamics in photo-induced chemical reactions with new methodologies. In this chapter, we introduce the time-resolved pump-probe experiments on gas-phase targets with FEL facilities to image the nuclear and electronic motions in molecular reactions, which serve as a benchmark for further FEL applications like coherent diffraction imaging and coherent control of functional dynamics in complex molecular reactions.

  4. Modeling of nonlinear physiological systems with fast and slow dynamics. II. Application to cerebral autoregulation.

    PubMed

    Mitsis, G D; Zhang, R; Levine, B D; Marmarelis, V Z

    2002-04-01

    Dynamic autoregulation of cerebral hemodynamics in healthy humans is studied using the novel methodology of the Laguerre-Volterra network for systems with fast and slow dynamics (Mitsis, G. D., and V. Z. Marmarelis, Ann. Biomed. Eng. 30:272-281, 2002). Since cerebral autoregulation is mediated by various physiological mechanisms with significantly different time constants, it is used to demonstrate the efficacy of the new method. Results are presented in the time and frequency domains and reveal that cerebral autoregulation is a nonlinear and dynamic (frequency-dependent) system with considerable nonstationarities. Quantification of the latter reveals greater variability in specific frequency bands for each subject in the low and middle frequency range (below 0.1 Hz). The nonlinear dynamics are prominent also in the low and middle frequency ranges, where the frequency response of the system exhibits reduced gain. PMID:12086006

  5. Relationship of fast- and slow-timescale neuronal dynamics in human MEG and SEEG.

    PubMed

    Zhigalov, Alexander; Arnulfo, Gabriele; Nobili, Lino; Palva, Satu; Palva, J Matias

    2015-04-01

    A growing body of evidence suggests that the neuronal dynamics are poised at criticality. Neuronal avalanches and long-range temporal correlations (LRTCs) are hallmarks of such critical dynamics in neuronal activity and occur at fast (subsecond) and slow (seconds to hours) timescales, respectively. The critical dynamics at different timescales can be characterized by their power-law scaling exponents. However, insight into the avalanche dynamics and LRTCs in the human brain has been largely obtained with sensor-level MEG and EEG recordings, which yield only limited anatomical insight and results confounded by signal mixing. We investigated here the relationship between the human neuronal dynamics at fast and slow timescales using both source-reconstructed MEG and intracranial stereotactical electroencephalography (SEEG). Both MEG and SEEG revealed avalanche dynamics that were characterized parameter-dependently by power-law or truncated-power-law size distributions. Both methods also revealed robust LRTCs throughout the neocortex with distinct scaling exponents in different functional brain systems and frequency bands. The exponents of power-law regimen neuronal avalanches and LRTCs were strongly correlated across subjects. Qualitatively similar power-law correlations were also observed in surrogate data without spatial correlations but with scaling exponents distinct from those of original data. Furthermore, we found that LRTCs in the autonomous nervous system, as indexed by heart-rate variability, were correlated in a complex manner with cortical neuronal avalanches and LRTCs in MEG but not SEEG. These scalp and intracranial data hence show that power-law scaling behavior is a pervasive but neuroanatomically inhomogeneous property of neuronal dynamics in central and autonomous nervous systems.

  6. Relationship of fast- and slow-timescale neuronal dynamics in human MEG and SEEG.

    PubMed

    Zhigalov, Alexander; Arnulfo, Gabriele; Nobili, Lino; Palva, Satu; Palva, J Matias

    2015-04-01

    A growing body of evidence suggests that the neuronal dynamics are poised at criticality. Neuronal avalanches and long-range temporal correlations (LRTCs) are hallmarks of such critical dynamics in neuronal activity and occur at fast (subsecond) and slow (seconds to hours) timescales, respectively. The critical dynamics at different timescales can be characterized by their power-law scaling exponents. However, insight into the avalanche dynamics and LRTCs in the human brain has been largely obtained with sensor-level MEG and EEG recordings, which yield only limited anatomical insight and results confounded by signal mixing. We investigated here the relationship between the human neuronal dynamics at fast and slow timescales using both source-reconstructed MEG and intracranial stereotactical electroencephalography (SEEG). Both MEG and SEEG revealed avalanche dynamics that were characterized parameter-dependently by power-law or truncated-power-law size distributions. Both methods also revealed robust LRTCs throughout the neocortex with distinct scaling exponents in different functional brain systems and frequency bands. The exponents of power-law regimen neuronal avalanches and LRTCs were strongly correlated across subjects. Qualitatively similar power-law correlations were also observed in surrogate data without spatial correlations but with scaling exponents distinct from those of original data. Furthermore, we found that LRTCs in the autonomous nervous system, as indexed by heart-rate variability, were correlated in a complex manner with cortical neuronal avalanches and LRTCs in MEG but not SEEG. These scalp and intracranial data hence show that power-law scaling behavior is a pervasive but neuroanatomically inhomogeneous property of neuronal dynamics in central and autonomous nervous systems. PMID:25834062

  7. Fast Imaging Technique to Study Drop Impact Dynamics of Non-Newtonian Fluids

    PubMed Central

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

    2014-01-01

    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. PMID:24637404

  8. Dynamic effect of sodium-water reaction in fast flux test facility power addition sodium pipes

    SciTech Connect

    Huang, S.N.; Anderson, M.J.

    1990-03-01

    The Fast Flux Facility (FFTF) is a demonstration and test facility of the sodium-cooled fast breeder reactor. A power addition'' to the facility is being considered to convert some of the dumped, unused heat into electricity generation. Components and piping systems to be added are sodium-water steam generators, sodium loop extensions from existing dump heat exchangers to sodium-water steam generators, and conventional water/steam loops. The sodium loops can be subjected to the dynamic loadings of pressure pulses that are caused by postulated sodium leaks and subsequent sodium-water reaction in the steam generator. The existing FFTF secondary pipes and the new power addition sodium loops were evaluated for exposure to the dynamic effect of the sodium-water reaction. Elastic and simplified inelastic dynamic analyses were used in this feasibility study. The results indicate that both the maximum strain and strain range are within the allowable limits. Several cycles of the sodium-water reaction can be sustained by the sodium pipes that are supported by ordinary pipe supports and seismic restraints. Expensive axial pipe restraints to withstand the sodium-water reaction loads are not needed, because the pressure-pulse-induced alternating bending stresses act as secondary stresses and the pressure pulse dynamic effect is a deformation-controlled quantity and is self-limiting. 14 refs., 7 figs., 3 tabs.

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

    PubMed

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

    2014-01-01

    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.

  10. 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

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

    PubMed

    Curtin, N A; Edman, K A

    1989-06-01

    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.

  12. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

    Nanosecond electrical explosion of fine metal wires in vacuum generates calibrated, radially expanded gas cylinders of metal atoms surrounded by a low-density fast expanding plasma corona. An integrated-phase technique, based on laser interferometry, provides the dynamic dipole polarizability of metal atoms. These data were previously unavailable for tungsten atoms. An extremely high melting temperature and significant premelt electronic emission make these measurements particularly complicated for this refractory metal. Most attempts to vaporize tungsten wire by electrical current pulse result in the disintegration of the sample into macro- and microfragments. However, application of a very fast-rising current, ˜1 kA /ns , can vaporize a thin 10-15 μm-diameter tungsten wire and generate a calibrated gas-plasma cylinder. Adding a dielectric coating to the wire leads to increased energy deposition to the wire core and a reduction of the surrounding plasma corona. Employing the integrated-phase technique on a fast-exploding coated tungsten wire, we find that the dynamic dipole polarizability of tungsten atoms at a wavelength of 532 nm equals 15 ±1.3 Å3 .

  14. Adaptive Movement Compensation for In Vivo Imaging of Fast Cellular Dynamics within a Moving Tissue

    PubMed Central

    Dufour, Hugues; De Koninck, Paul; De Koninck, Yves; Côté, Daniel

    2011-01-01

    In vivo non-linear optical microscopy has been essential to advance our knowledge of how intact biological systems work. It has been particularly enabling to decipher fast spatiotemporal cellular dynamics in neural networks. The power of the technique stems from its optical sectioning capability that in turn also limits its application to essentially immobile tissue. Only tissue not affected by movement or in which movement can be physically constrained can be imaged fast enough to conduct functional studies at high temporal resolution. Here, we show dynamic two-photon Ca2+ imaging in the spinal cord of a living rat at millisecond time scale, free of motion artifacts using an optical stabilization system. We describe a fast, non-contact adaptive movement compensation approach, applicable to rough and weakly reflective surfaces, allowing real-time functional imaging from intrinsically moving tissue in live animals. The strategy involves enslaving the position of the microscope objective to that of the tissue surface in real-time through optical monitoring and a closed feedback loop. The performance of the system allows for efficient image locking even in conditions of random or irregular movements. PMID:21629702

  15. Fast Quantum Molecular Dynamics Simulations of Simple Organic Liquids under Shock Compression

    NASA Astrophysics Data System (ADS)

    Cawkwell, Marc; Niklasson, Anders; Manner, Virginia; McGrane, Shawn; Dattelbaum, Dana

    2013-06-01

    The responses of liquid formic acid, acrylonitrile, and nitromethane to shock compression have been studied using quantum-based molecular dynamics simulations with the self-consistent tight-binding code LATTE. Microcanonical Born-Oppenheimer trajectories with precise energy conservation were computed without relying on an iterative self-consistent field optimization of the electronic degrees of freedom at each time step via the Fast Quantum Mechanical Molecular Dynamics formalism. The input shock pressures required to initiate chemistry in our simulations agree very well with recent laser- and flyer-plate-driven shock compression experiments. On-the-fly analysis of the electronic structure of the liquids over hundreds of picoseconds after dynamic compression revealed that their reactivity is strongly correlated with the temperature and pressure dependence of their HOMO-LUMO gap.

  16. Global solution for a kinetic chemotaxis model with internal dynamics and its fast adaptation limit

    NASA Astrophysics Data System (ADS)

    Liao, Jie

    2015-12-01

    A nonlinear kinetic chemotaxis model with internal dynamics incorporating signal transduction and adaptation is considered. This paper is concerned with: (i) the global solution for this model, and, (ii) its fast adaptation limit to Othmer-Dunbar-Alt type model. This limit gives some insight to the molecular origin of the chemotaxis behaviour. First, by using the Schauder fixed point theorem, the global existence of weak solution is proved based on detailed a priori estimates, under quite general assumptions. However, the Schauder theorem does not provide uniqueness, so additional analysis is required to be developed for uniqueness. Next, the fast adaptation limit of this model is derived by extracting a weak convergence subsequence in measure space. For this limit, the first difficulty is to show the concentration effect on the internal state. Another difficulty is the strong compactness argument on the chemical potential, which is essential for passing the nonlinear kinetic equation to the weak limit.

  17. 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.

  18. 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. PMID:25461588

  19. Numerical continuation of canard orbits in slow-fast dynamical systems

    NASA Astrophysics Data System (ADS)

    Desroches, M.; Krauskopf, B.; Osinga, H. M.

    2010-03-01

    A trajectory of a system with two clearly separated time scales generally consists of fast segments (or jumps) followed by slow segments where the trajectory follows an attracting part of a slow manifold. The switch back to fast dynamics typically occurs when the trajectory passes a fold with respect to a fast direction. A special role is played by trajectories known as canard orbits, which do not jump at a fold but, instead, follow a repelling slow manifold for some time. We concentrate here on the case of a slow-fast system with two slow and one fast variable, where canard orbits arise geometrically as intersection curves of two-dimensional attracting and repelling slow manifolds. Canard orbits are intimately related to the dynamics near special points known as folded singularities, which in turn have been shown to explain small-amplitude oscillations that can be found as part of so-called mixed-mode oscillations. In this paper we present a numerical method to detect and then follow branches of canard orbits in a system parameter. More specifically, we define well-posed two-point boundary value problems (BVPs) that represent orbit segments on the slow manifolds, and we continue their solution families with the package AUTO. In this way, we are able to deal effectively with the numerical challenge of strong attraction to and strong repulsion from the slow manifolds. Canard orbits are detected as the transverse intersection points of the curves along which attracting and repelling slow manifolds intersect a suitable section (near a folded node). These intersection points correspond to a unique pair of orbits segments, one on the attracting and one on the repelling slow manifold. After concatenation of the respective pairs of orbit segments, all detected canard orbits are represented as solutions of a single BVP, which allows us to continue them in system parameters. We demonstrate with two examples—the self-coupled FitzHugh-Nagumo system and a three

  20. Fast Chebyshev-polynomial method for simulating the time evolution of linear dynamical systems.

    PubMed

    Loh, Y L; Taraskin, S N; Elliott, S R

    2001-05-01

    We present a fast method for simulating the time evolution of any linear dynamical system possessing eigenmodes. This method does not require an explicit calculation of the eigenvectors and eigenfrequencies, and is based on a Chebyshev polynomial expansion of the formal operator matrix solution in the eigenfrequency domain. It does not suffer from the limitations of ordinary time-integration methods, and can be made accurate to almost machine precision. Among its possible applications are harmonic classical mechanical systems, quantum diffusion, and stochastic transport theory. An example of its use is given for the problem of vibrational wave-packet propagation in a disordered lattice. PMID:11415044

  1. 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.

  2. Dynamics of dust-free cavities behind fast projectiles in a dusty plasma under microgravity conditions

    SciTech Connect

    Caliebe, D.; Arp, O.; Piel, A.

    2011-07-15

    The penetration of a dusty plasma by fast charged projectiles is studied under microgravity conditions. The mass and charge of the projectiles are larger than those of the target particles. A projectile generates a dust-free cavity in its wake, whose shape strongly depends on the projectile velocity. The faster the projectile the more elongated becomes the cavity while its cross-section decreases. The opening time of the cavity is found independent of the projectile velocity. For supersonic projectiles, the dynamics of the cavity can be decomposed into an initial impulse and a subsequent elastic response that can be modeled by a damped harmonic oscillator.

  3. Fast dynamics and relaxation of colloidal drops during the drying process using multispeckle diffusing wave spectroscopy.

    PubMed

    Lee, Jeong Yong; Hwang, Ji Won; Jung, Hyun Wook; Kim, Sung Hyun; Lee, Seong Jae; Yoon, Kisun; Weitz, David A

    2013-01-22

    The fast dynamics generated by the Brownian motion of particles in colloidal drops, and the related relaxation during drying, which play key roles in suspension systems, were investigated incorporating multispeckle diffusing wave spectroscopy (MSDWS). MSDWS equipment was implemented to analyze the relaxation properties of suspensions under a nonergodic and nonstationary drying process, which cannot be elucidated by conventional light scattering methods, such as dynamic light scattering and diffusing wave spectroscopy. Rapid particle movement can be identified by the characteristic relaxation time, which is closely related to the Brownian motion due to thermal fluctuations of the particles. In the compacting stage of the drying process, the characteristic relaxation time increased gradually with the drying time because the particles in the colloidal drop were constrained by themselves. Moreover, variations of the initial concentration and particle size considerably affected the complete drying time and characteristic relaxation time, producing a shorter relaxation time for a low concentrated suspension with small particles. PMID:23281633

  4. Earthquake signatures from fast slip and dynamic fracture propagation: state of the art

    NASA Astrophysics Data System (ADS)

    Griffith, W. A.; Rowe, C. D.

    2014-12-01

    Earthquakes are dynamic slip events that propagate along fault surfaces, radiating seismic waves. The majority of energy released is expended in heating and breaking of rocks along the fault. The fracture damage is linked to transient stress conditions at the rupture tip which only exist during dynamic slip, while the frictional heating depends on high velocity slip behind the rupture tip to generate heat energy faster than it can be dissipated, causing transient local temperature rise. One might think that extensive damage and alteration would result, creating an unambiguous geological fingerprint, but in fact, there are few unequivocal indicators for past seismic slip. In 1999, the rare fault rock pseudotachylyte (melt formed when frictional heating exceeds the solidus) was the only accepted evidence (Cowan, 1999). Recently, more indicators of fossilized earthquakes have been proposed. We define "evidence of past earthquakes" as evidence of either fast fault slip (at rates that only occur during earthquakes) or evidence of the propagation of dynamic rupture. We first summarize advances made in identifying evidence in the rock record of fast slip. Much of the work during the past 15 years has focused on integrating carefully controlled laboratory friction experiments, and constraints from numerical modeling, with field observations in an attempt to re-create structures observed in fault rocks and then relate these to the specific boundary conditions required to form them in the laboratory. This approach has yielded a number of advances in identifying textures and geochemical signatures diagnostic of fast slip via temperature rises which may not reach the bulk melting temperature of the fault rocks. Next, we focus on damage near the tip of shear ruptures propagating at velocities characteristic of earthquakes, an approach which has received less attention in the geological literature than fast slip but is equally diagnostic. Finally, we try to frame some of the

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

    PubMed

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

    2012-08-01

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

  6. 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.

  7. Fast dynamics of cortical functional and effective connectivity during word reading.

    PubMed

    Bedo, Nicolas; Ribary, Urs; Ward, Lawrence M

    2014-01-01

    We describe for the first time the fast dynamics of functional and effective (causal) connectivity during word reading. Independent component analysis of high-density EEG recorded during a word reading task recovered multiple sources of electrical brain activity previously identified by fMRI and PET. Results confirmed the ventral occipito-temporal cortex (vOT) as a central hub for word reading, showing a progression of theta-band (3-7 Hz) and gamma-band (30-50 Hz) phase synchronization and directed theta-band and gamma-band information flow with both early visual areas and high-level language-processing areas. These results highlight the interplay between local and long-distance neural dynamics involved at each stage of the reading process. Moreover, these measures of functional and causal connectivity dynamics may be used as a benchmark for comparison with clinical populations (e.g. individuals with developmental dyslexia), such that disturbances in connectivity dynamics may provide insight as to underlying neurological problems with language processing, and their potential remediation.

  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. A dynamic prescribed vortex wake model for the FAST/AeroDyn wind energy conversion simulation code

    NASA Astrophysics Data System (ADS)

    Currin, Hugh D.

    2007-12-01

    A Dynamic Prescribed Vortex Wake model for analysis of horizontal axis wind turbines has been developed. This model extends the HAWTDAWG steady state prescribed wake code to dynamic flows. This extension assumes wake vortices follow prescription functions valid at the time each vortex is generated. This allows modeling of dynamic wake effects known to exist. This assumption is supported through analysis and comparison to UAE Phase VI test data. The new Dynamic Prescribed Vortex Wake model is built into AeroDyn as a third aerodynamic model and uses the FAST structural dynamic model. It implements the wind models and dynamic stall model in AeroDyn. FAST structural degrees of freedom are implemented. Comparisons are made to UAE Phase VI wind tunnel data, and to the other two AeroDyn models, Blade Element Momentum and Generalized Dynamic Wake. Both steady, to verify the base model, and dynamic, to validate the extension to dynamic flow, conditions are considered. Both axial and yawed flow are analyzed. Dynamic UAE test data analyzed include rapid pitch, Sequence Q, and yaw release, Sequence E. The Dynamic Prescribed Wake model compares favorably to test data and to other AeroDyn models. Small rapid dynamic response is noted in each model and the test data. The new Dynamic Prescribed Vortex Wake model shows promise. Release of the code for experimental use and further validation is recommended.

  10. 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.

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

    DOE PAGES

    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 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. 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.

  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. Platelet Activating Factor Enhances Synaptic Vesicle Exocytosis Via PKC, Elevated Intracellular Calcium, and Modulation of Synapsin 1 Dynamics and Phosphorylation

    PubMed Central

    Hammond, Jennetta W.; Lu, Shao-Ming; Gelbard, Harris A.

    2016-01-01

    Platelet activating factor (PAF) is an inflammatory phospholipid signaling molecule implicated in synaptic plasticity, learning and memory and neurotoxicity during neuroinflammation. However, little is known about the intracellular mechanisms mediating PAF’s physiological or pathological effects on synaptic facilitation. We show here that PAF receptors are localized at the synapse. Using fluorescent reporters of presynaptic activity we show that a non-hydrolysable analog of PAF (cPAF) enhances synaptic vesicle release from individual presynaptic boutons by increasing the size or release of the readily releasable pool and the exocytosis rate of the total recycling pool. cPAF also activates previously silent boutons resulting in vesicle release from a larger number of terminals. The underlying mechanism involves elevated calcium within presynaptic boutons and protein kinase C activation. Furthermore, cPAF increases synapsin I phosphorylation at sites 1 and 3, and increases dispersion of synapsin I from the presynaptic compartment during stimulation, freeing synaptic vesicles for subsequent release. These findings provide a conceptual framework for how PAF, regardless of its cellular origin, can modulate synapses during normal and pathologic synaptic activity. PMID:26778968

  15. 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. PMID:27475398

  16. 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.

  17. Differences in intracellular calcium dynamics cause differences in α-granule secretion and phosphatidylserine expression in platelets adhering on glass and TiO2.

    PubMed

    Gupta, Swati; Donati, Alessia; Reviakine, Ilya

    2016-06-01

    In this study, the activation of purified human platelets due to their adhesion on glass and TiO2 in the absence of extracellular calcium was investigated. Differences in α-granule secretion between platelets adhering on the two surfaces were detected by examining the expression and secretion of the α-granule markers P-selectin (CD62P) and β-thromboglobulin. Similarly, differences in the expression of phosphatidylserine (PS), and in the activation of the major integrin GPIIb/IIIa, on the surfaces of the adhering platelets, were also observed. While all of these activation markers were expressed in platelets adhering on glass, the surface markers were not expressed in platelets adhering on TiO2, and β-thromboglobulin secretion levels were substantially reduced. Differences in marker expression and secretion correlated with differences in the intracellular calcium dynamics. Calcium ionophore treatment triggered α-granule secretion and PS expression in TiO2-adhering platelets but had no effect on the activation of GPIIb/IIIa. These results demonstrate specificity in the way surfaces of artificial materials activate platelets, link differences in the intracellular calcium dynamics observed in the platelets adhering on the two surfaces to the differences in some of the platelet responses (α-granule secretion and PS expression), but also highlight the involvement of synergistic, calcium-independent pathways in platelet activation. The ability to control activation in surface-adhering platelets makes this an attractive model system for studying platelet signaling pathways and for tissue engineering applications. PMID:27124595

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Fast and reliable decisions for a dynamic song parameter in field crickets.

    PubMed

    Trobe, Daniela; Schuster, Richard; Römer, Heiner

    2011-01-01

    We investigated the choice of female crickets for a dynamic song parameter (chirp rate) on a walking compensator, and the underlying neuronal basis for the choice in the form of discharge differences in the pair of AN1-neurons driving the phonotactic steering behaviour. Our analysis reveals that decisions about chirp rate in a choice situation are made fast and reliably by female crickets. They steered towards the higher chirp rate after a delay of only 2.2-6 s, depending on the rate difference between the song alternatives. In this time period, the female experienced only one to two additional chirps in the song model with the higher rate. There was a strong correlation between the accumulated AN1 discharge difference and the amount of steering towards the side with the stronger response. PMID:20878165

  6. Fast and reliable decisions for a dynamic song parameter in field crickets

    PubMed Central

    Trobe, Daniela; Schuster, Richard; Römer, Heiner

    2014-01-01

    We investigated the choice of female crickets for a dynamic song parameter (chirp rate) on a walking compensator, and the underlying neuronal basis for the choice in the form of discharge differences in the pair of AN1-neurons driving the phonotactic steering behaviour. Our analysis reveals that decisions about chirp rate in a choice situation are made fast and reliably by female crickets. They steered towards the higher chirp rate after a delay of only 2.2–6 s, depending on the rate difference between the song alternatives. In this time period, the female experienced only one to two additional chirps in the song model with the higher rate. There was a strong correlation between the accumulated AN1 discharge difference and the amount of steering towards the side with the stronger response. PMID:20878165

  7. Fast and reliable decisions for a dynamic song parameter in field crickets.

    PubMed

    Trobe, Daniela; Schuster, Richard; Römer, Heiner

    2011-01-01

    We investigated the choice of female crickets for a dynamic song parameter (chirp rate) on a walking compensator, and the underlying neuronal basis for the choice in the form of discharge differences in the pair of AN1-neurons driving the phonotactic steering behaviour. Our analysis reveals that decisions about chirp rate in a choice situation are made fast and reliably by female crickets. They steered towards the higher chirp rate after a delay of only 2.2-6 s, depending on the rate difference between the song alternatives. In this time period, the female experienced only one to two additional chirps in the song model with the higher rate. There was a strong correlation between the accumulated AN1 discharge difference and the amount of steering towards the side with the stronger response.

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

    PubMed

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

    2016-04-01

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

  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. Impact of Fast Sodium Channel Inactivation on Spike Threshold Dynamics and Synaptic Integration

    PubMed Central

    Platkiewicz, Jonathan; Brette, Romain

    2011-01-01

    Neurons spike when their membrane potential exceeds a threshold value. In central neurons, the spike threshold is not constant but depends on the stimulation. Thus, input-output properties of neurons depend both on the effect of presynaptic spikes on the membrane potential and on the dynamics of the spike threshold. Among the possible mechanisms that may modulate the threshold, one strong candidate is Na channel inactivation, because it specifically impacts spike initiation without affecting the membrane potential. We collected voltage-clamp data from the literature and we found, based on a theoretical criterion, that the properties of Na inactivation could indeed cause substantial threshold variability by itself. By analyzing simple neuron models with fast Na inactivation (one channel subtype), we found that the spike threshold is correlated with the mean membrane potential and negatively correlated with the preceding depolarization slope, consistent with experiments. We then analyzed the impact of threshold dynamics on synaptic integration. The difference between the postsynaptic potential (PSP) and the dynamic threshold in response to a presynaptic spike defines an effective PSP. When the neuron is sufficiently depolarized, this effective PSP is briefer than the PSP. This mechanism regulates the temporal window of synaptic integration in an adaptive way. Finally, we discuss the role of other potential mechanisms. Distal spike initiation, channel noise and Na activation dynamics cannot account for the observed negative slope-threshold relationship, while adaptive conductances (e.g. K+) and Na inactivation can. We conclude that Na inactivation is a metabolically efficient mechanism to control the temporal resolution of synaptic integration. PMID:21573200

  11. Fast Quantum Molecular Dynamics Simulations of Shock-induced Chemistry in Organic Liquids

    NASA Astrophysics Data System (ADS)

    Cawkwell, Marc

    2014-03-01

    The responses of liquid formic acid and phenylacetylene to shock compression have been investigated via quantum-based molecular dynamics simulations with the self-consistent tight-binding code LATTE. Microcanonical Born-Oppenheimer trajectories with precise conservation of the total energy were computed without relying on an iterative self-consistent field optimization of the electronic degrees of freedom at each time step via the Fast Quantum Mechanical Molecular Dynamics formalism [A. M. N. Niklasson and M. J. Cawkwell, Phys. Rev. B, 86, 174308 (2012)]. The conservation of the total energy in our trajectories was pivotal for the capture of adiabatic shock heating as well as temperature changes arising from endo- or exothermic chemistry. Our self-consistent tight-binding parameterizations yielded very good predictions for the gas-phase geometries of formic acid and phenylacetylene molecules and the principal Hugoniots of the liquids. In accord with recent flyer-plate impact experiments, our simulations revealed i) that formic acid reacts at relatively low impact pressures but with no change in volume between products and reactants, and ii) a two-step polymerization process for phenylacetylene. Furthermore, the evolution of the HOMO-LUMO gap tracked on-the-fly during our simulations could be correlated with changes transient absorption measured during laser-driven shock compression experiments on these liquids.

  12. 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.

  13. Dynamic fast terminal sliding mode control of a shape memory alloy actuated system

    NASA Astrophysics Data System (ADS)

    Marathe, Meeshawn S.; Srinivasan, S. M.

    2016-04-01

    In this paper we address the chattering phenomenon which is a common drawback associated with the normal Sliding Mode Control (SMC) law for a basic shape memory alloy (SMA) actuated system. A new method has been proposed to counter this effect by combining the concepts of Fast Terminal SMC and Dynamic controller. A phenomenological model is developed for the SMA which incorporates a piecewise linear hysteresis behavior. This model is used for both open loop as well as closed loop simulations for a linear motion control system. Based on this model, a dynamic terminal sliding mode control law is derived and applied to the system. A normal SMC law with saturation function which is known to reduce chattering is compared with the proposed control law for its effectiveness to curb the issue of chattering versus its ability to faithfully track a desired trajectory. Numerical Simulations indicate that the proposed law is able to reduce the chattering effect sufficiently and at par with the control technique involving saturation function.

  14. Single-cell and population level viral infection dynamics revealed by phageFISH, a method to visualize intracellular and free viruses.

    PubMed

    Allers, Elke; Moraru, Cristina; Duhaime, Melissa B; Beneze, Erica; Solonenko, Natalie; Barrero-Canosa, Jimena; Amann, Rudolf; Sullivan, Matthew B

    2013-08-01

    Microbes drive the biogeochemical cycles that fuel planet Earth, and their viruses (phages) alter microbial population structure, genome repertoire, and metabolic capacity. However, our ability to understand and quantify phage-host interactions is technique-limited. Here, we introduce phageFISH - a markedly improved geneFISH protocol that increases gene detection efficiency from 40% to > 92% and is optimized for detection and visualization of intra- and extracellular phage DNA. The application of phageFISH to characterize infection dynamics in a marine podovirus-gammaproteobacterial host model system corroborated classical metrics (qPCR, plaque assay, FVIC, DAPI) and outperformed most of them to reveal new biology. PhageFISH detected both replicating and encapsidated (intracellular and extracellular) phage DNA, while simultaneously identifying and quantifying host cells during all stages of infection. Additionally, phageFISH allowed per-cell relative measurements of phage DNA, enabling single-cell documentation of infection status (e.g. early vs late stage infections). Further, it discriminated between two waves of infection, which no other measurement could due to population-averaged signals. Together, these findings richly characterize the infection dynamics of a novel model phage-host system, and debut phageFISH as a much-needed tool for studying phage-host interactions in the laboratory, with great promise for environmental surveys and lineage-specific population ecology of free phages. PMID:23489642

  15. 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

  16. Fast analysis of molecular dynamics trajectories with graphics processing units—Radial distribution function histogramming

    NASA Astrophysics Data System (ADS)

    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.

  17. 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

  18. 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.

  19. 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. PMID:26567653

  20. 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.

  1. Dynamic visual acuity and coincidence-anticipation timing by experienced and inexperienced women players of fast pitch softball.

    PubMed

    Millslagle, D G

    2000-04-01

    This study examined the relationship between dynamic visual acuity and coincidence-anticipation timing in 16 inexperienced and 16 experienced women's fast pitch softball players. Pearson-product correlations indicated a low relationship between dynamic visual acuity and coincidence-anticipation timing. The correlations for dynamic visual acuity and coincidence anticipation between experienced and inexperienced dynamic visual acuity were not significant. A significant difference was found between the mean dynamic visual acuity of the two groups, i.e., experienced players had better dynamic visual acuity than inexperienced players. Analysis of variance of constant errors, variable errors, and absolute errors of coincidence anticipation indicated no significant differences between groups or across the three accuracy scores. The interaction between experience and accuracy was not significant.

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

    PubMed

    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 1mm spatial resolution but low imaging speed (10min 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. PMID:27498337

  3. 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.

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

    PubMed

    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(3)-10(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. PMID:25770527

  5. 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.

  6. Fast photonic information processing using semiconductor lasers with delayed optical feedback: role of phase dynamics.

    PubMed

    Nguimdo, Romain Modeste; Verschaffelt, Guy; Danckaert, Jan; Van der Sande, Guy

    2014-04-01

    Semiconductor lasers subject to delayed optical feedback have recently shown great potential in solving computationally hard tasks. By optically implementing a neuro-inspired computational scheme, called reservoir computing, based on the transient response to optical data injection, high processing speeds have been demonstrated. While previous efforts have focused on signal bandwidths limited by the semiconductor laser's relaxation oscillation frequency, we demonstrate numerically that the much faster phase response makes significantly higher processing speeds attainable. Moreover, this also leads to shorter external cavity lengths facilitating future on-chip implementations. We numerically benchmark our system on a chaotic time-series prediction task considering two different feedback configurations. The results show that a prediction error below 4% can be obtained when the data is processed at 0.25 GSamples/s. In addition, our insight into the phase dynamics of optical injection in a semiconductor laser also provides a clear understanding of the system performance at different pump current levels, even below solitary laser threshold. Considering spontaneous emission noise and noise in the readout layer, we obtain good prediction performance at fast processing speeds for realistic values of the noise strength.

  7. Development of Multi-GeV Electron Radiography for Measurements of Fast, Dynamic Systems

    NASA Astrophysics Data System (ADS)

    Merrill, Frank; Danly, Christopher; Fabritius, Joseph; Mariam, Fesseha; Poulson, Daniel; Simpson, Raspberry; Walstrom, Peter; Wilde, Carl

    2015-06-01

    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 will 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. A radiography system to make these measurements is being designed for measurements at the SLAC accelerator facility. We will present the plans for these measurements along with an estimate from simulations of the performance characteristics of a future capability.

  8. 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.

  9. 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

  10. Dynamics of fast pattern formation in porous silicon by laser interference

    SciTech Connect

    Peláez, Ramón J.; Kuhn, Timo; Afonso, Carmen N.; Vega, Fidel

    2014-10-20

    Patterns are fabricated on 290 nm thick nanostructured porous silicon layers by phase-mask laser interference using single pulses of an excimer laser (193 nm, 20 ns pulse duration). The dynamics of pattern formation is studied by measuring in real time the intensity of the diffraction orders 0 and 1 at 633 nm. The results show that a transient pattern is formed upon melting at intensity maxima sites within a time <30 ns leading to a permanent pattern in a time <100 ns upon solidification at these sites. This fast process is compared to the longer one (>1 μs) upon melting induced by homogeneous beam exposure and related to the different scenario for releasing the heat from hot regions. The diffraction efficiency of the pattern is finally controlled by a combination of laser fluence and initial thickness of the nanostructured porous silicon layer and the present results open perspectives on heat release management upon laser exposure as well as have potential for alternative routes for switching applications.

  11. Dynamics of action potential firing in electrically connected striatal fast-spiking interneurons

    PubMed Central

    Russo, Giovanni; Nieus, Thierry R.; Maggi, Silvia; Taverna, Stefano

    2013-01-01

    Fast-spiking interneurons (FSIs) play a central role in organizing the output of striatal neural circuits, yet functional interactions between these cells are still largely unknown. Here we investigated the interplay of action potential (AP) firing between electrically connected pairs of identified FSIs in mouse striatal slices. In addition to a loose coordination of firing activity mediated by membrane potential coupling, gap junctions (GJ) induced a frequency-dependent inhibition of spike discharge in coupled cells. At relatively low firing rates (2–20 Hz), some APs were tightly synchronized whereas others were inhibited. However, burst firing at intermediate frequencies (25–60 Hz) mostly induced spike inhibition, while at frequencies >50–60 Hz FSI pairs tended to synchronize. Spike silencing occurred even in the absence of GABAergic synapses or persisted after a complete block of GABAA receptors. Pharmacological suppression of presynaptic spike afterhyperpolarization (AHP) caused postsynaptic spikelets to become more prone to trigger spikes at near-threshold potentials, leading to a mostly synchronous firing activity. The complex pattern of functional coordination mediated by GJ endows FSIs with peculiar dynamic properties that may be critical in controlling striatal-dependent behavior. PMID:24294191

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

    SciTech Connect

    Chou, W.; Tajima, C.T.; Matsumoto, R. |; Shibata, K.

    1998-01-01

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

  13. Activation of the recombinant human alpha 7 nicotinic acetylcholine receptor significantly raises intracellular free calcium.

    PubMed

    Delbono, O; Gopalakrishnan, M; Renganathan, M; Monteggia, L M; Messi, M L; Sullivan, J P

    1997-01-01

    The alpha 7 nicotinic acetylcholine receptor (nAChR) subtype, unlike other neuronal nicotinic receptors, exhibits a relatively high permeability to Ca++ ions. Although Ca++ entry through this receptor subtype has been implicated in various Ca(++)-dependent processes in the central nervous system, little is known about how this receptor modulates mammalian intracellular Ca++ dynamics. Intracellular Ca++ responses evoked by activation of the human alpha 7 nAChRs stably expressed in HEK-293 (human embryonic kidney) cells were studied. Inward current and intracellular Ca++ transients were recorded simultaneously in response to a fast drug application system. Current recordings under whole-cell voltage-clamp and fast ratiometric intracellular Ca++ imaging acquisition were synchronized to drug pulses. The mean peak [Ca++]i observed with 100 microM (-)-nicotine was 356 +/- 48 nM (n = 8). The magnitude of the intracellular Ca++ elevation corresponds to a 20% fractional current carried by Ca++ ions. The EC50 of the intracellular Ca++ responses for (-)-nicotine, (+/-)-epibatidine, 1,1 dimethyl-4-phenyl-piperazinium and acetylcholine were 51, 3.5, 75 and 108 microM, respectively. These EC50 values strongly correlate with those recorded for the cationic inward current through alpha 7 nAChR. alpha-Bungarotoxin, methyllcaconitine or extracellular Ca++ chelation ablated (-)-nicotine-evoked increase in intracellular Ca++ concentration. This study provides evidence that cation influx through the human alpha 7 nAChR is sufficient to mediate a significant, transient, rise in intracellular Ca++ concentration.

  14. 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.

  15. 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.

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

    PubMed

    Maslennikov, Oleg V; Nekorkin, Vladimir I

    2016-07-01

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

  17. Dynamic arrays for fast, efficient, data manipulation during image analysis: a new software tool for exploratory data analysis.

    PubMed

    Breen, E J; Joss, G H; Williams, K L

    1992-03-01

    Memory reallocation is used to construct a run-time data structure for fast/efficient storage of information during collection and analysis. The data structure presented uses dynamic memory but does not require the use of pointers to link nodes of information together. It allows for simple and efficient access to data via array indexing rather than through the use of lists or tree structures and it provides flexibility for competing storage requirements that are determined dynamically. The data structure is developed in the C programming language and a suite of ANSI standard C subroutines that make up a run-time data structure management system is provided.

  18. Stat3 isoforms, alpha and beta, demonstrate distinct intracellular dynamics with prolonged nuclear retention of Stat3beta mapping to its unique C-terminal end.

    PubMed

    Huang, Ying; Qiu, Jihui; Dong, Shuo; Redell, Michele S; Poli, Valeria; Mancini, Michael A; Tweardy, David J

    2007-11-30

    Two isoforms of Stat3 (signal transducer and activator of transcription 3) are expressed in cells, alpha (p92) and beta (p83), both derived from a single gene by alternative mRNA splicing. The 55-residue C-terminal transactivation domain of Stat3alpha is deleted in Stat3beta and replaced by seven unique C-terminal residues (CT7) whose function remains uncertain. We subcloned the open reading frames of Stat3alpha and Stat3beta into the C terminus of green fluorescent protein (GFP). Fluorescent microscopic analysis of HEK293T cells transiently transfected with GFP-Stat3alpha or GFP-Stat3beta revealed similar kinetics and cytokine concentration dependence of nuclear accumulation; these findings were confirmed by high throughput microscope analysis of murine embryonic fibroblasts that lacked endogenous Stat3 but stably expressed either GFP-Stat3alpha or GFP-Stat3beta. However, although time to half-maximal cytoplasmic reaccumulation after cytokine withdrawal was 15 min for GFP-Stat3alpha, it was >180 min for GFP-Stat3beta. Furthermore, although the intranuclear mobility of GFP-Stat3alpha was rapid and increased with cytokine stimulation, the intranuclear mobility of GFP-Stat3beta in unstimulated cells was slower than that of GFP-Stat3alpha in unstimulated cells and was slowed further following cytokine stimulation. Deletion of the unique CT7 domain from Stat3beta eliminated prolonged nuclear retention but did not alter its intranuclear mobility. Thus, Stat3alpha and Stat3beta have distinct intracellular dynamics, with Stat3beta exhibiting prolonged nuclear retention and reduced intranuclear mobility especially following ligand stimulation. Prolonged nuclear retention, but not reduced intranuclear mobility, mapped to the CT7 domain of Stat3beta.

  19. First measurements of D{sub α} spectrum produced by anisotropic fast ions in the gas dynamic trap

    SciTech Connect

    Lizunov, A.; Anikeev, A.

    2014-11-15

    Angled injection of eight deuterium beams in gas dynamic trap (GDT) plasmas builds up the population of fast ions with the distribution function, which conserves a high degree of initial anisotropy in space, energy, and pitch angle. Unlike the Maxwellian distribution case, the fast ion plasma component in GDT cannot be exhaustively characterized by the temperature and density. The instrumentation complex to study of fast ions is comprised of motional Stark effect diagnostic, analyzers of charge exchange atoms, and others. The set of numerical codes using for equilibrium modeling is also an important tool of analysis. In the recent campaign of summer 2014, we recorded first signals from the new fast ion D-alpha diagnostic on GDT. This paper presents the diagnostic description and results of pilot measurements. The diagnostic has four lines of sight, distributed across the radius of an axially symmetric plasma column in GDT. In the present setup, a line-integrated optical signal is measured in each channel. In the transverse direction, the spatial resolution is 18 mm. Collected light comes to the grating spectrometer with the low-noise detector based on a charge-coupled device matrix. In the regime of four spectra stacked vertically on the sensor, the effective spectral resolution of measurements is approximately 0.015 nm. Exposure timing is provided by the fast optical ferroelectric crystal shutter, allowing frames of duration down to 70 μs. This number represents the time resolution of measurements. A large dynamic range of the camera permits for a measurement of relatively small light signals produced by fast ions on top of the bright background emission from the bulk plasma. The fast ion emission has a non-Gaussian spectrum featuring the characteristic width of approximately 4 nm, which can be separated from relatively narrow Gaussian lines of D-alpha and H-alpha coming from the plasma periphery, and diagnostic beam emission. The signal to noise ratio varies

  20. 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.

    2014-01-01

    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.

  1. 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.

  2. 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.; Goupee, A. J.

    2014-01-01

    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

  3. Cooperative dynamics in coupled systems of fast and slow phase oscillators.

    PubMed

    Sakaguchi, Hidetsugu; Okita, Takayuki

    2016-02-01

    We propose a coupled system of fast and slow phase oscillators. We observe two-step transitions to quasiperiodic motions by direct numerical simulations of this coupled oscillator system. A low-dimensional equation for order parameters is derived using the Ott-Antonsen ansatz. The applicability of the ansatz is checked by the comparison of numerical results of the coupled oscillator system and the reduced low-dimensional equation. We investigate further several interesting phenomena in which mutual interactions between the fast and slow oscillators play an essential role. Fast oscillations appear intermittently as a result of excitatory interactions with slow oscillators in a certain parameter range. Slow oscillators experience an oscillator-death phenomenon owing to their interaction with fast oscillators. This oscillator death is explained as a result of saddle-node bifurcation in a simple phase equation obtained using the temporal average of the fast oscillations. Finally, we show macroscopic synchronization of the order 1:m between the slow and fast oscillators.

  4. Fast dynamic response of the fermentative metabolism of Escherichia coli to aerobic and anaerobic glucose pulses.

    PubMed

    Lara, Alvaro R; Taymaz-Nikerel, Hilal; Mashego, Mlawule R; van Gulik, Walter M; Heijnen, Joseph J; Ramírez, Octavio T; van Winden, Wouter A

    2009-12-15

    The response of Escherichia coli cells to transient exposure (step increase) in substrate concentration and anaerobiosis leading to mixed-acid fermentation metabolism was studied in a two-compartment bioreactor system consisting of a stirred tank reactor (STR) connected to a mini-plug-flow reactor (PFR: BioScope, 3.5 mL volume). Such a system can mimic the situation often encountered in large-scale, fed-batch bioreactors. The STR represented the zones of a large-scale bioreactor that are far from the point of substrate addition and that can be considered as glucose limited, whereas the PFR simulated the region close to the point of substrate addition, where glucose concentration is much higher than in the rest of the bioreactor. In addition, oxygen-poor and glucose-rich regions can occur in large-scale bioreactors. The response of E. coli to these large-scale conditions was simulated by continuously pumping E. coli cells from a well stirred, glucose limited, aerated chemostat (D = 0.1 h(-1)) into the mini-PFR. A glucose pulse was added at the entrance of the PFR. In the PFR, a total of 11 samples were taken in a time frame of 92 s. In one case aerobicity in the PFR was maintained in order to evaluate the effects of glucose overflow independently of oxygen limitation. Accumulation of acetate and formate was detected after E. coli cells had been exposed for only 2 s to the glucose-rich (aerobic) region in the PFR. In the other case, the glucose pulse was also combined with anaerobiosis in the PFR. Glucose overflow combined with anaerobiosis caused the accumulation of formate, acetate, lactate, ethanol, and succinate, which were also detected as soon as 2 s after of exposure of E. coli cells to the glucose and O(2) gradients. This approach (STR-mini-PFR) is useful for a better understanding of the fast dynamic phenomena occurring in large-scale bioreactors and for the design of modified strains with an improved behavior under large-scale conditions. PMID:19685524

  5. Fast dynamic response of the fermentative metabolism of Escherichia coli to aerobic and anaerobic glucose pulses.

    PubMed

    Lara, Alvaro R; Taymaz-Nikerel, Hilal; Mashego, Mlawule R; van Gulik, Walter M; Heijnen, Joseph J; Ramírez, Octavio T; van Winden, Wouter A

    2009-12-15

    The response of Escherichia coli cells to transient exposure (step increase) in substrate concentration and anaerobiosis leading to mixed-acid fermentation metabolism was studied in a two-compartment bioreactor system consisting of a stirred tank reactor (STR) connected to a mini-plug-flow reactor (PFR: BioScope, 3.5 mL volume). Such a system can mimic the situation often encountered in large-scale, fed-batch bioreactors. The STR represented the zones of a large-scale bioreactor that are far from the point of substrate addition and that can be considered as glucose limited, whereas the PFR simulated the region close to the point of substrate addition, where glucose concentration is much higher than in the rest of the bioreactor. In addition, oxygen-poor and glucose-rich regions can occur in large-scale bioreactors. The response of E. coli to these large-scale conditions was simulated by continuously pumping E. coli cells from a well stirred, glucose limited, aerated chemostat (D = 0.1 h(-1)) into the mini-PFR. A glucose pulse was added at the entrance of the PFR. In the PFR, a total of 11 samples were taken in a time frame of 92 s. In one case aerobicity in the PFR was maintained in order to evaluate the effects of glucose overflow independently of oxygen limitation. Accumulation of acetate and formate was detected after E. coli cells had been exposed for only 2 s to the glucose-rich (aerobic) region in the PFR. In the other case, the glucose pulse was also combined with anaerobiosis in the PFR. Glucose overflow combined with anaerobiosis caused the accumulation of formate, acetate, lactate, ethanol, and succinate, which were also detected as soon as 2 s after of exposure of E. coli cells to the glucose and O(2) gradients. This approach (STR-mini-PFR) is useful for a better understanding of the fast dynamic phenomena occurring in large-scale bioreactors and for the design of modified strains with an improved behavior under large-scale conditions.

  6. Monitoring the Oxygen Dynamics of Brain Tissue In Vivo by Fast Acousto-Optic Scanning Microscopy: A Proposed Instrument.

    PubMed

    Zhou, Zhenqiao; Chen, Dayu; Huang, Zhiqiang; Wang, Shaofang; Zeng, Shaoqun

    2016-01-01

    The function of the brain neural circuit is highly dependent on oxygen supply. Imaging the precise oxygen distribution and dynamics are critical for understanding the relationship between neuronal activity and oxygen dynamics of the nearby capillaries. Here, we develop fast acousto-optic scanning two-photon microscopy. Combined with oxygen probes, such as PtP-C343, we can monitor oxygen dynamics at the submicron level by this real-time microscopy. In this fast acousto-optic scanning microscopy, an acousto-optic deflector (AOD), an inertia-less scanner, is used to scan the femtosecond laser. A cylindrical lens is used to compensate the 'cylindrical lens effect' of AOD and a prism is used to compensate the chromatic dispersion of AOD. An electro-optical modulator (EOM) and a sCMOS camera are gated to measure the phosphorescence lifetime. With a 40× water objective lens, this set-up can image a 100 μm × 100 μm field of view at a speed of 20 frames per second and a 25 μm × 8 μm field of view at a speed of 500 frames per second. This real-time two-photon microscopy is expected to be a good tool for observing and recording the precise rapid oxygen dynamics in the cerebral cortex, which will facilitate studies of oxygen metabolism in neurosciences. PMID:27526168

  7. A new dynamic mode for fast imaging in atomic force microscopes

    NASA Astrophysics Data System (ADS)

    Mohan, Gayathri

    Video-rate imaging and property sensing with nanoscale precision is a subject of immense interest to scientists because it facilitates a deep understanding of processes and sample properties at a molecular level. This dissertation addresses the challenges of high-bandwidth imaging and real-time estimation of sample properties in an atomic force microscope (AFM). Atomic force microscopy has enabled high-resolution nanoscale imaging and manipulation of mechanical, biological and chemical properties of samples at atomic scales. However, current atomic force microscopy techniques suffer from limited imaging bandwidths making them impractical for applications requiring high throughput. A dynamic mode of imaging that achieves high imaging speeds while preserving the properties of high resolution and low forcing on the samples is developed. The proposed imaging scheme is particularly significant with the advent of high-speed nanopositioning stages and electronics. The design is accomplished by model-based force regulation that utilizes the fast cantilever de ection signal instead of its slower derivative signals used in existing methods. The control design uses the vertical and dither (shake) piezo-actuators to make the probe de ection signal track an appropriately designed trajectory. The underlying idea is to treat the nonlinear tip-sample interaction forces as an extraneous disturbance and derive an optimal control design for disturbance rejection with emphasis on robustness. The tracking objective guarantees force regulation between the probe-tip and the sample. Hinfinity stacked sensitivity framework is used to impose the control objectives and the optimal controller is derived through multiobjective optimization. The control design achieves disturbance rejection bandwidths of 0.15 -- 0.20 times the first modal frequency of cantilever used for imaging. Consequently, in the presence of appropriate lateral positioning bandwidth, imaging speeds of the order of 15 -- 20

  8. 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.

  9. 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.

  10. Short-term fasting affects luteinizing hormone secretory dynamics but not reproductive function in normal-weight sedentary women.

    PubMed

    Olson, B R; Cartledge, T; Sebring, N; Defensor, R; Nieman, L

    1995-04-01

    Acute food withdrawal reversibly inhibits the hypothalamic-pituitary-gonadal axis in men and in rhesus monkeys, and it produces defects in LH pulsatility in normal-weight women. However, the clinical effect of short-term nutritional deprivation on the reproductive axis of normally cycling women has not been evaluated. Thus we studied the effect of a 3-day fast during the midfollicular phase on menstrual cycle length, gonadotropin secretory patterns, follicular development, and ovulation. After a baseline ovulatory cycle, 12 women within 15% of ideal body weight were randomized to be fed (n = 7) or fasted (n = 10) on cycle days 7 to 9. Five of the women repeated the study and received the alternate diet. Endocrine and metabolic parameters of fasting and reproductive physiology were measured on cycle days 6 to 12. Fasted physiology was demonstrated by characteristic alterations in growth hormone, insulin-like growth factor I, TSH, and T3 levels. During fed cycles, the number of LH pulses remained constant on cycle days 6, 9 and 11, whereas mean LH levels, LH area under the curve, and LH pulse amplitude increased significantly over this time (all P < 0.05). In contrast, fasted cycles were marked by a significant decrease in the number of LH pulses on the last day of the fast (cycle day 9, P < 0.05) and by a lack of increase over time of mean LH values, LH area under the curve, and LH pulse amplitude. Follicle development, as assessed by daily ultrasound examination and estradiol measurements, was similar in all cycles and was followed by ovulation in all women; follicular and luteal phase lengths of fasted and fed cycles were similar. We conclude that the alterations in LH secretory dynamics that occur during a 3-day fast are not sufficient to perturb follicle development and cycle lengths in normal-weight sedentary women. The resilience of the reproductive axis in these healthy women contrasts with the sensitivity of the hypothalamic-pituitary-gonadal axis to acute

  11. 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

  12. 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.

  13. Structural Dynamics of Soluble Chloride Intracellular Channel Protein CLIC1 Examined by Amide Hydrogen-Deuterium Exchange Mass Spectrometry (DXMS)†

    PubMed Central

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

    2009-01-01

    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 destabilising 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 α1. This helix is intrinsically stable and is most likely retained in the membrane conformation. Strand β2, 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. PMID:19650640

  14. 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

  15. Intracellular Bacteria in Protozoa

    NASA Astrophysics Data System (ADS)

    Görtz, Hans-Dieter; Brigge, Theo

    Intracellular bacteria in humans are typically detrimental, and such infections are regarded by the patients as accidental and abnormal. In protozoa it seems obvious that many bacteria have coevolved with their hosts and are well adapted to the intracellular way of life. Manifold interactions between hosts and intracellular bacteria are found, and examples of antibacterial resistance of unknown mechanisms are observed. The wide diversity of intracellular bacteria in protozoa has become particularly obvious since they have begun to be classified by molecular techniques. Some of the bacteria are closely related to pathogens; others are responsible for the production of toxins.

  16. 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.

  17. Lysosome targeting fluorescence probe for imaging intracellular thiols.

    PubMed

    Kand, Dnyaneshwar; Saha, Tanmoy; Lahiri, Mayurika; Talukdar, Pinaki

    2015-08-14

    A BODIPY-based fluorescence turn-on probe, exhibiting high selectivity and sensitivity towards intracellular thiols with excellent lysosomal localization is reported. The probe displayed fast response towards biothiols in aqueous solution. Localization of the probe in lysosome was demonstrated by intracellular colocalization studies with the aid of LysoSensor Green.

  18. Validation of a Fast-Fluid-Dynamics Model for Predicting Distribution of Particles with Low Stokes Number

    SciTech Connect

    Zuo, Wangda; Chen, Qingyan

    2011-06-01

    To design a healthy indoor environment, it is important to study airborne particle distribution indoors. As an intermediate model between multizone models and computational fluid dynamics (CFD), a fast fluid dynamics (FFD) model can be used to provide temporal and spatial information of particle dispersion in real time. This study evaluated the accuracy of the FFD for predicting transportation of particles with low Stokes number in a duct and in a room with mixed convection. The evaluation was to compare the numerical results calculated by the FFD with the corresponding experimental data and the results obtained by the CFD. The comparison showed that the FFD could capture major pattern of particle dispersion, which is missed in models with well-mixed assumptions. Although the FFD was less accurate than the CFD partially due to its simplification in numeric schemes, it was 53 times faster than the CFD.

  19. Comparison of the morphometric dynamics of fast-growing and slow-growing strains of turbot Scophthalmus maximus

    NASA Astrophysics Data System (ADS)

    Wang, Xin'an; Ma, Aijun

    2015-07-01

    The dynamics of changes in body shape of fast-growing and slow-growing strains of turbot Scophthalmus maximus, and of the differences in body shape between the two strains, were evaluated from 3 to 27 months of age. The ratios of total length/body length, body width/body length and total length/body width were used as morphometric indices. The two strains exhibited different temporal trends in total length/body length but similar trends in body width/body length and total length/body width. Generally, body width/body length of the two strains increased with time and total length/body width decreased. Thus, the bodies of both fast-growing and slow-growing strains of turbot changed from a narrow to a more rounded shape. However, the ratio total length/body length was generally lower, body width/body length was mostly higher and total length/body width was consistently lower in the fast-growing strain than in the slow-growing strain. Correlation analysis of the three shape ratios with body weight showed that total length/body length and total length/body width were unsuitable, and that width/body length was suitable, for use as a phenotypic marker for selective breeding of turbot for growth in weight.

  20. 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.

  1. 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.

  2. LASER-driven fast electron dynamics in gaseous media under the influence of large electric fields

    NASA Astrophysics Data System (ADS)

    Batani, D.; Baton, S. D.; Manclossi, M.; Piazza, D.; Koenig, M.; Benuzzi-Mounaix, A.; Popescu, H.; Rousseaux, C.; Borghesi, M.; Cecchetti, C.; Schiavi, A.

    2009-03-01

    We present the results of experiments performed at the LULI laboratory, using the 100 TW laser facility, on the study of the propagation of fast electrons in gas targets. The implemented diagnostics included chirped shadowgraphy and proton imaging. Proton images showed the presence of very large fields in the gas (produced by charge separation). In turn, these imply a strong inhibition of propagation, and a slowing down of the fast electron cloud as it penetrates in the gas. Indeed chirped shadowgraphy images show a reduction in time of the velocity of the electron cloud from the initial value, of the order of a fraction of c, over a time scale of a few picoseconds.

  3. 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.

  4. Fiber-optic system for monitoring fast photoactivation dynamics of optical highlighter fluorescent proteins.

    PubMed

    Pei, Zhiguo; Qin, Lingsong; Zhang, Zhihong; Zeng, Shaoqun; Huang, Zhen-Li

    2011-08-01

    Characterizing the photoactivation performance of optical highlighter fluorescent proteins is crucial to the realization of photoactivation localization microscopy. In contrast to those fluorescence-based approaches that require complex data processing and calibration procedures, here we report a simple and quantitative alternative, which relies on the measurement of small absorption spectra changes over time with a fiber-optic system. Using Dronpa as a representative highlighter protein, we have investigated the capacity of this system in monitoring the fast photoactivation process.

  5. 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.

  6. 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

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

    PubMed

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

    2009-10-01

    A fast Fourier transform (FFT) based wide range millimeter wave diagnostics for spectral characterization of scattered millimeter waves in plasmas has been successfully brought into operation. The scattered millimeter waves are heterodyne downconverted and directly digitized using a fast analog-digital converter and a compact peripheral component interconnect computer. Frequency spectra are obtained by FFT in the time domain of the intermediate frequency signal. The scattered millimeter waves are generated during high power electron cyclotron resonance heating experiments on the TEXTOR tokamak and demonstrate the performance of the diagnostics and, in particular, the usability of direct digitizing and Fourier transformation of millimeter wave signals. The diagnostics is able to acquire 4 GHz wide spectra of signals in the range of 136-140 GHz. The rate of spectra is tunable and has been tested between 200,000 spectra/s with a frequency resolution of 100 MHz and 120 spectra/s with a frequency resolution of 25 kHz. The respective dynamic ranges are 52 and 88 dB. Major benefits of the new diagnostics are a tunable time and frequency resolution due to postdetection, near-real time processing of the acquired data. This diagnostics has a wider application in astrophysics, earth observation, plasma physics, and molecular spectroscopy for the detection and analysis of millimeter wave radiation, providing high-resolution spectra at high temporal resolution and large dynamic range. PMID:19895061

  8. Discrete-state representation of ion permeation coupled to fast gating in a model of ClC chloride channels: comparison to multi-ion continuous space Brownian dynamics simulations.

    PubMed

    Coalson, Rob D; Cheng, Mary Hongying

    2010-01-28

    A discrete-state model of chloride ion motion in a ClC chloride channel is constructed, following a previously developed multi-ion continuous space model of the same system (Cheng, M. H.; Mamonov, A. B.; Dukes, J. W.; Coalson, R. D. J. Phys. Chem. B 2007, 111, 5956) that included a simplistic representation of the fast gate in this channel. The reducibility of the many-body continuous space to the eight discrete-state model considered in the present work is examined in detail by performing three-dimensional Brownian dynamics simulations of each allowed state-to-state transition in order to extract the appropriate rate constant for this process, and then inserting the pairwise rate constants thereby obtained into an appropriate set of kinetic master equations. Experimental properties of interest, including the rate of Cl(-) ion permeation through the open channel and the average rate of closing of the fast gate as a function of bulk Cl(-) ion concentrations in the intracellular and extracellular electrolyte reservoirs are computed. Good agreement is found between the results obtained via the eight discrete-state model versus the multi-ion continuous space model, thereby encouraging continued development of the discrete-state model to include more complex behaviors observed experimentally in these channels.

  9. 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

    2015-09-01

    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.

  10. A sharp thermal transition of fast aromatic ring dynamics in ubiquitin

    PubMed Central

    Kasinath, Vignesh; Fu, Yinan; Sharp, Kim A.

    2015-01-01

    Aromatic amino acid side chains have a rich role within proteins and are often central to their structure and function. Suitable isotopic labelling strategies enable studies of sub-nanosecond aromatic ring dynamics using solution NMR relaxation methods. Surprisingly, we find that the three aromatic side chains in human ubiquitin show a sharp thermal dynamical transition at ~312 K. Hydrostatic pressure has little effect on the low temperature behaviour but decreases somewhat the amplitude of motion in the high temperature regime. Thus below the transition temperature ring motion is largely librational. Above it complete ring rotation that is most consistent with a continuous rotational diffusion not requiring transient creation of a large activated free volume occurs. Molecular dynamics simulations qualitatively corroborate this view and reinforce the notion that the dynamical character of the protein interior has a much more liquid alkane-like properties than previously appreciated. PMID:25476230

  11. 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.

  12. 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.

  13. 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.

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

    PubMed

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

    2012-06-21

    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)] 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. PMID:22779579

  15. Ultra-fast excitation dynamics in low bandgap polymer solar cell

    NASA Astrophysics Data System (ADS)

    Wang, Ying-hui; Zou, Lu; Kang, Zhi-hui; Qian, Cheng; Ma, Yu-guang; Zhang, Han-zhuang

    2013-08-01

    The photovoltaic performance and the photo-physical behaviors based on Poly{2,7'-9,9-dioctylfluorene-alt-5-diethylhexyl-3,6-bis(5-bromothiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4-dione}:PC61BM heterojunction have been studied in detail. The photocurrent and voltage of devices obviously improve after increasing the amount of PC61BM in heterojunction. The transient absorption data exhibit that the dissociation processes of excitons is fast, but that of the charge transfer (CT) state is complicate and owns two paths according to the energy of CT state. In the first situation, the free charge may be directly dissociated from the high energy CT states and its generation rate is too fast to be observed in our detection window. In the low energy CT states, the dissociation process slows down, which is estimated to be 20.8 ps at room temperature. The exciton dissociation in the blend film is so efficient that it could directly take place before exciton-exiton annihilation process at high excitation intensity.

  16. Fast Dynamics and Stabilization of Proteins: Binary Glasses of Trehalose and Glycerol

    PubMed Central

    Cicerone, Marcus T.; Soles, Christopher L.

    2004-01-01

    We present elastic and inelastic incoherent neutron scattering data from a series of trehalose glasses diluted with glycerol. A strong correlation with recently published protein stability data in the same series of glasses illustrates that the dynamics at Q ≥ 0.71 Å−1 and ω > 200 MHz are important to stabilization of horseradish peroxidase and yeast alcohol dehydrogenase in these glasses. To the best of our knowledge, this is the first direct evidence that enzyme stability in a room temperature glass depends upon suppressing these short-length scale, high-frequency dynamics within the glass. We briefly discuss the coupling of protein motions to the local dynamics of the glass. Also, we show that Tg alone is not a good indicator for the protein stability in this series of glasses; the glass that confers the maximum room-temperature stability does not have the highest Tg. PMID:15189880

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

    NASA Astrophysics Data System (ADS)

    Wu, Xia; Wu, Genhua

    2014-08-01

    Geometrical optimization of atomic clusters is performed by a development of adaptive immune optimization algorithm (AIOA) with dynamic lattice searching (DLS) operation (AIOA-DLS method). By a cycle of construction and searching of the dynamic lattice (DL), DLS algorithm rapidly makes the clusters more regular and greatly reduces the potential energy. DLS can thus be used as an operation acting on the new individuals after mutation operation in AIOA to improve the performance of the AIOA. The AIOA-DLS method combines the merit of evolutionary algorithm and idea of dynamic lattice. The performance of the proposed method is investigated in the optimization of Lennard-Jones clusters within 250 atoms and silver clusters described by many-body Gupta potential within 150 atoms. Results reported in the literature are reproduced, and the motif of Ag61 cluster is found to be stacking-fault face-centered cubic, whose energy is lower than that of previously obtained icosahedron.

  18. Simultaneous fast measurement of circuit dynamics at multiple sites across the mammalian brain.

    PubMed

    Kim, Christina K; Yang, Samuel J; Pichamoorthy, Nandini; Young, Noah P; Kauvar, Isaac; Jennings, Joshua H; Lerner, Talia N; Berndt, Andre; Lee, Soo Yeun; Ramakrishnan, Charu; Davidson, Thomas J; Inoue, Masatoshi; Bito, Haruhiko; Deisseroth, Karl

    2016-04-01

    Real-time activity measurements from multiple specific cell populations and projections are likely to be important for understanding the brain as a dynamical system. Here we developed frame-projected independent-fiber photometry (FIP), which we used to record fluorescence activity signals from many brain regions simultaneously in freely behaving mice. We explored the versatility of the FIP microscope by quantifying real-time activity relationships among many brain regions during social behavior, simultaneously recording activity along multiple axonal pathways during sensory experience, performing simultaneous two-color activity recording, and applying optical perturbation tuned to elicit dynamics that match naturally occurring patterns observed during behavior.

  19. 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.

  20. Chronic impact of sulfamethoxazole on acetate utilization kinetics and population dynamics of fast growing microbial culture.

    PubMed

    Kor-Bicakci, G; Pala-Ozkok, I; Rehman, A; Jonas, D; Ubay-Cokgor, E; Orhon, D

    2014-08-01

    The study evaluated the chronic impact of sulfamethoxazole on metabolic activities of fast growing microbial culture. It focused on changes induced on utilization kinetics of acetate and composition of the microbial community. The experiments involved a fill and draw reactor, fed with acetate and continuous sulfamethoxazole dosing of 50 mg/L. The evaluation relied on model evaluation of the oxygen uptake rate profiles, with parallel assessment of microbial community structure by 454-pyrosequencing. Continuous sulfamethoxazole dosing inflicted a retardation effect on acetate utilization in a way commonly interpreted as competitive inhibition, blocked substrate storage and accelerated endogenous respiration. A fraction of acetate was utilized at a much lower rate with partial biodegradation of sulfamethoxazole. Results of pyrosequencing with a replacement mechanism within a richer more diversified microbial culture, through inactivation of vulnerable fractions in favor of species resistant to antibiotic, which made them capable of surviving and competing even with a slower metabolic response.

  1. 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.

  2. 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

  3. 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

  4. Dynamic NMR of low-sensitivity fast-relaxing nuclei: (17)O NMR and DFT study of acetoxysilanes.

    PubMed

    Fusaro, Luca; Mameli, Giulia; Mocci, Francesca; Luhmer, Michel; Cerioni, Giovanni

    2012-02-01

    (17)O NMR is not routinely used for structure characterization, and kinetic studies of fluxional organic compounds are seldom undertaken because poor sensitivity and fast quadrupole relaxation are frequently regarded as intractable issues. This work shows how, nowadays, quantitative (17)O dynamic NMR studies on small organic molecules are feasible without enrichment being needed. It reports on acetoxysilanes, a class of fluxional compounds whose structure and dynamics were to be clarified. Natural abundance (17)O NMR spectra were recorded over a wide range of temperatures using standard instrumentation. The analysis relies on simple linewidth measurements and directly provides the activation parameters. The activation enthalpy is found to decrease with increasing number of acetoxy groups bound to silicon. Density functional theory calculations properly predict this trend and show that a single oxygen atom of the acetoxy group is bound to silicon, excluding chelation as binding mode, and that the dynamic process involves the shift of the silicon atom between the two oxygen atoms of the acetoxy group.

  5. Effects of body mass, meal size, fast length, and temperature on specific dynamic action in the timber rattlesnake (Crotalus horridus).

    PubMed

    Zaidan, Frederic; Beaupre, Steven J

    2003-01-01

    Detailed analysis of animal energy budgets requires information on the cost of digestion (specific dynamic action [SDA]), which can represent a significant proportion of ingested energy (up to 30% in infrequent feeders). We studied the effects of snake mass, temperature (25 degrees and 30 degrees C), fasting time (1 and 5 mo), and prey size (10%-50% of snake mass) on SDA in 26 timber rattlesnakes (Crotalus horridus). We used flow-through respirometry to measure hourly CO(2) production rates (VCO2) for 1 d before and up to 17 d after feeding. Crotalus horridus, like previously studied viperids and boids, show large and ecologically relevant increases in metabolism due to feeding. Depending on treatment and individual, VCO2 increased to 2.8-11.8 times the resting metabolic rate within 12-45 h postfeeding and decreased to baseline within 4.3-15.4 d. Significant effects of snake mass, meal mass, and fast length were detected. Increased temperature decreased the time required to complete the process but had little effect on total energy expended on SDA. Energy expended on SDA increased with increasing fast length, snake mass, and prey mass. Considering all of our data, we found that a simple allometric relationship explained 96.7% of the variation in total CO(2) production during SDA. Calculations suggest that energy devoted to SDA may approach 20% of the total annual energy budget of snakes in nature. Discrepancies between our data and some previous studies draw attention to the fact that the measurement, expression, and analysis of SDA may be sensitive to several methodological and statistical assumptions.

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

    PubMed

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

    2016-01-01

    The paper presents the benefits of using fast adiabatic passage for the study of molecular dynamics in the solid state heteronuclear systems in the laboratory frame. A homemade pulse spectrometer operating at the frequency of 30.2MHz and 28.411MHz for protons and fluorines, respectively, has been enhanced with microcontroller direct digital synthesizer DDS controller [1-4]. This work briefly describes how to construct a low-cost and easy-to-assemble adiabatic extension set for homemade and commercial spectrometers based on recently very popular Arduino shields. The described set was designed for fast adiabatic generation. Timing and synchronization problems are discussed. The cross-relaxation experiments with different initial states of the two spin systems have been performed. Contrary to our previous work [5] where the steady-state NOE experiments were conducted now proton spins (1)H are polarized in the magnetic field B0 while fluorine spins (19)F are perturbed by selective saturation for a short time and then the system is allowed to evolve for a period in the absence of a saturating field. The adiabatic passage application leads to a reversal of magnetization of fluorine spins and increases the amplitude of the signal. PMID:26705906

  7. 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.

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

    PubMed

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

    2016-01-01

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

  9. Fast characterization of functionalized silica materials by silicon-29 surface-enhanced NMR spectroscopy using dynamic nuclear polarization.

    PubMed

    Lelli, Moreno; Gajan, David; Lesage, Anne; Caporini, Marc A; Vitzthum, Veronika; Miéville, Pascal; Héroguel, Florent; Rascón, Fernando; Roussey, Arthur; Thieuleux, Chloé; Boualleg, Malika; Veyre, Laurent; Bodenhausen, Geoffrey; Copéret, Christophe; Emsley, Lyndon

    2011-02-23

    We demonstrate fast characterization of the distribution of surface bonding modes and interactions in a series of functionalized materials via surface-enhanced nuclear magnetic resonance spectroscopy using dynamic nuclear polarization (DNP). Surface-enhanced silicon-29 DNP NMR spectra were obtained by using incipient wetness impregnation of the sample with a solution containing a polarizing radical (TOTAPOL). We identify and compare the bonding topology of functional groups in materials obtained via a sol-gel process and in materials prepared by post-grafting reactions. Furthermore, the remarkable gain in time provided by surface-enhanced silicon-29 DNP NMR spectroscopy (typically on the order of a factor 400) allows the facile acquisition of two-dimensional correlation spectra. PMID:21280606

  10. Asymptotic global fast dynamics and attractor fractal dimension of the TDGL-equations of superconductivity

    NASA Astrophysics Data System (ADS)

    Willie, Robert

    2016-09-01

    In this paper, we study a model system of equations of the time dependent Ginzburg-Landau equations of superconductivity in a Lorentz gauge, in scale of Hilbert spaces E^{α } with initial data in E^{β } satisfying 3α + β ≥ N/2, where N=2,3 is such that the spatial domain of the equations [InlineEquation not available: see fulltext.]. We show in the asymptotic dynamics of the equations, well-posedness of the dynamical system for a global exponential attractor {{U}}subset E^{α } compact in E^{β } if α >β , uniform differentiability of orbits on the attractor in E0\\cong L2, and the existence of an explicit finite bounding estimate on the fractal dimension of the attractor yielding that its Hausdorff dimension is as well finite. Uniform boundedness in (0,∞ )× Ω of solutions in E^{1/2}\\cong H1(Ω ) is in addition investigated.

  11. Fast and noise-resistant ion-trap quantum computation with inherent dynamical decoupling

    NASA Astrophysics Data System (ADS)

    Zheng, Shi-Biao

    2014-02-01

    We propose a scheme for realizing quantum logic gates between any pair of ions confined in a linear trap with a pair of laser beams tuned to the carrier. The striking feature of the scheme is that the carrier excitation accompanying the spin-motion coupling does not affect the gate dynamics. As a consequence, the gate not only is much more insensitive to motional heating but also can operate at a higher speed compared to the previous schemes. The other important advantages are that the gate speed does not need to be inversely proportional to the number of ions in the chain, and the accompanying carrier drive results in dynamical decoupling, making the gate performance robust against dephasing noises. We show that for the same error sources the gate infidelity can be decreased by about ten times compared with previous schemes.

  12. 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. PMID:24093278

  13. Intracellular parcel service: current issues in intracellular membrane trafficking.

    PubMed

    Herrmann, Johannes M; Spang, Anne

    2015-01-01

    Eukaryotic cells contain a multitude of membrane structures that are connected through a highly dynamic and complex exchange of their constituents. The vibrant instability of these structures challenges the classical view of defined, static compartments that are connected by different types of vesicles. Despite this astonishing complexity, proteins and lipids are accurately transported into the different intracellular membrane systems. Over the past few decades many factors have been identified that either mediate or regulate intracellular membrane trafficking. Like in a modern parcel sorting system of a logistics center, the cargo typically passes through several sequential sorting stations until it finally reaches the location that is specified by its individual address label. While each membrane system employs specific sets of factors, the transport processes typically operate on common principles. With the advent of genome- and proteome-wide screens, the availability of mutant collections, exciting new developments in microscope technology and sophisticated methods to study their dynamics, the future promises a broad and comprehensive picture of the processes by which eukaryotic cells sort their proteins.

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

    NASA Astrophysics Data System (ADS)

    Sannino, Francesco

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

  15. 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.

  16. 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

  17. Variations in the Fast Folding Rates of the λ-Repressor: A Hybrid Molecular Dynamics Study

    PubMed Central

    Pogorelov, Taras V.; Luthey-Schulten, Zaida

    2004-01-01

    The ability to predict the effects of mutations on protein folding rates and mechanisms would greatly facilitate folding studies. Using a realistic full atom potential coupled with a G\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}{\\mathrm{{\\bar {o}}}}\\end{equation*}\\end{document}-like potential biased to the native state structure, we have investigated the effects of point mutations on the folding rates of a small single domain protein. The hybrid potential provides a detailed level of description of the folding mechanism that we correlate to features of the folding energy landscapes of fast and slow mutants of an 80-residue-long fragment of the λ-repressor. Our computational reconstruction of the folding events is compared to the recent experimental results of W. Y. Yang and M. Gruebele (see companion article) and T. G. Oas and co-workers on the λ-repressor, and helps to clarify the differences observed in the folding mechanisms of the various mutants. PMID:15240458

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

    SciTech Connect

    Atkinson, P. Eddrief, M.; Etgens, V. H.; Khemliche, H. Debiossac, M.; Mulier, M.; Lalmi, B.; Roncin, P.; Momeni, A.

    2014-07-14

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

  19. Lossless compression of very large volume data with fast dynamic access

    NASA Astrophysics Data System (ADS)

    Zhao, Rongkai; Tao, Tao; Gabriel, Michael; Belford, Geneva

    2002-09-01

    The volumetric data set is important in many scientific and biomedical fields. Since such sets may be extremely large, a compression method is critical to store and transmit them. To achieve a high compression rate, most of the existing volume compression methods are lossy, which is usually unacceptable in biomedical applications. We developed a new context-based non-linear prediction method to preprocess the volume data set in order to effectively lower the prediction entropy. The prediction error is further encoded using Huffman code. Unlike the conventional methods, the volume is divided into cubical blocks to take advantage of the data's spatial locality. Instead of building one Huffman tree for each block, we developed a novel binning algorithm that build a Huffman tree for each group (bin) of blocks. Combining all the effects above, we achieved an excellent compression rate compared to other lossless volume compression methods. In addition, an auxiliary data structure, Scalable Hyperspace File (SHSF) is used to index the huge volume so that we can obtain many other benefits including parallel construction, on-the-fly accessing of compressed data without global decompression, fast previewing, efficient background compressing, and scalability etc.

  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

    2013-12-01

    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. PMID:24514521

  1. 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.

  2. FAST TRACK COMMUNICATION: Relativistic echo dynamics and the stability of a beam of Landau electrons

    NASA Astrophysics Data System (ADS)

    Sadurní, E.; Seligman, T. H.

    2008-03-01

    We extend the concepts of echo dynamics and fidelity decay to relativistic quantum mechanics, specifically in the context of Klein-Gordon and Dirac equations under external electromagnetic fields. In both cases, we define similar expressions for the fidelity amplitude under perturbations of these fields and a covariant version of the echo operator. Transformation properties under the Lorentz group are established. An alternate expression for fidelity is given in the Dirac case in terms of a 4-current. As an application, we study a beam of Landau electrons perturbed by field inhomogeneities.

  3. A fast algorithm for calculating an expected outbreak size on dynamic contagion networks.

    PubMed

    Enright, Jessica; Kao, Rowland R

    2016-09-01

    Calculation of expected outbreak size of a simple contagion on a known contact network is a common and important epidemiological task, and is typically carried out by computationally intensive simulation. We describe an efficient exact method to calculate the expected outbreak size of a contagion on an outbreak-invariant network that is a directed and acyclic, allowing us to model all dynamically changing networks when contagion can only travel forward in time. We describe our algorithm and its use in pseudocode, as well as showing examples of its use on disease relevant, data-derived networks. PMID:27379615

  4. 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

    2013-12-01

    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.

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

    PubMed

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

    2014-10-27

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

  6. 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

  7. 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.

  8. Temperature dependence of fast carbonyl backbone dynamics in chicken villin headpiece subdomain.

    PubMed

    Vugmeyster, Liliya; Ostrovsky, Dmitry

    2011-06-01

    Temperature-dependence of protein dynamics can provide information on details of the free energy landscape by probing the characteristics of the potential responsible for the fluctuations. We have investigated the temperature-dependence of picosecond to nanosecond backbone dynamics at carbonyl carbon sites in chicken villin headpiece subdomain protein using a combination of three NMR relaxation rates: (13)C' longitudinal rate, and two cross-correlated rates involving dipolar and chemical shift anisotropy (CSA) relaxation mechanisms, (13)C'/(13)C'-(13)C(α) CSA/dipolar and (13)C'/(13)C'-(15)N CSA/dipolar. Order parameters have been extracted using the Lipari-Szabo model-free approach assuming a separation of the time scales of internal and molecular motions in the 2-16°C temperature range. There is a gradual deviation from this assumption from lower to higher temperatures, such that above 16°C the separation of the time scales is inconsistent with the experimental data and, thus, the Lipari-Szabo formalism can not be applied. While there are variations among the residues, on the average the order parameters indicate a markedly steeper temperature dependence at backbone carbonyl carbons compared to that probed at amide nitrogens in an earlier study. This strongly advocates for probing sites other than amide nitrogen for accurate characterization of the potential and other thermodynamics characteristics of protein backbone.

  9. AGIPD, a high dynamic range fast detector for the European XFEL

    NASA Astrophysics Data System (ADS)

    Allahgholi, A.; Becker, J.; Bianco, L.; Delfs, A.; Dinapoli, R.; Goettlicher, P.; Graafsma, H.; Greiffenberg, D.; Hirsemann, H.; Jack, S.; Klanner, R.; Klyuev, A.; Krueger, H.; Lange, S.; Marras, A.; Mezza, D.; Mozzanica, A.; Rah, S.; Xia, Q.; Schmitt, B.; Schwandt, J.; Sheviakov, I.; Shi, X.; Smoljanin, S.; Trunk, U.; Zhang, J.; Zimmer, M.

    2015-01-01

    AGIPD—(Adaptive Gain Integrating Pixel Detector) is a hybrid pixel X-ray detector developed by a collaboration between Deutsches Elektronen-Synchrotron (DESY), Paul-Scherrer-Institut (PSI), University of Hamburg and the University of Bonn. The detector is designed to comply with the requirements of the European XFEL. The radiation tolerant Application Specific Integrated Circuit (ASIC) is designed with the following highlights: high dynamic range, spanning from single photon sensitivity up to 104 12.5keV photons, achieved by the use of the dynamic gain switching technique using 3 possible gains of the charge sensitive preamplifier. In order to store the image data, the ASIC incorporates 352 analog memory cells per pixel, allowing also to store 3 voltage levels corresponding to the selected gain. It is operated in random-access mode at 4.5MHz frame rate. The data acquisition is done during the 99.4ms between the bunch trains. The AGIPD has a pixel area of 200× 200 μ m2 and a 500μ m thick silicon sensor is used. The architecture principles were proven in different experiments and the ASIC characterization was done with a series of development prototypes. The mechanical concept was developed in the close contact with the XFEL beamline scientists and is now being manufactured. A first single module system was successfully tested at APS.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

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

    PubMed

    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. 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+H(2)-->H(2)+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.

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

    PubMed

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

    2016-01-01

    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

  19. 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.

  20. 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

  1. Chloride Channels of Intracellular Membranes

    PubMed Central

    Edwards, John C.; Kahl, Christina R.

    2010-01-01

    Proteins implicated as intracellular chloride channels include the intracellular ClC proteins, the bestrophins, the cystic fibrosis transmembrane conductance regulator, the CLICs, and the recently described Golgi pH regulator. This paper examines current hypotheses regarding roles of intracellular chloride channels and reviews the evidence supporting a role in intracellular chloride transport for each of these proteins. PMID:20100480

  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. 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

    2015-01-01

    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. PMID:26437911

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

    PubMed Central

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

    2015-01-01

    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. PMID:26437911

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

    SciTech Connect

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

    2013-10-15

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

  6. Fast dynamical evolution of a hadron resonance gas via Hagedorn states

    NASA Astrophysics Data System (ADS)

    Beitel, M.; Greiner, C.; Stoecker, H.

    2016-08-01

    Hagedorn states are the key to understanding how all hadrons observed in high-energy heavy-ion collisions seem to reach thermal equilibrium so quickly. An assembly of Hagedorn states is formed in elementary hadronic or heavy-ion collisions at hadronization. Microscopic simulations within the transport model UrQMD allow us to study the time evolution of such a pure nonequilibrated Hagedorn state gas to a thermally equilibrated hadron resonance gas by using dynamics, which unlike strings fully respect detailed balance. Propagation, repopulation, rescatterings, and decays of Hagedorn states provide the yields of all hadrons up to a mass of m =2.5 GeV . Ratios of feed-down-corrected hadron multiplicities are compared to corresponding experimental data from the ALICE Collaboration at LHC. The quick thermalization within t =1 -2 fm /c of the emerging hadron resonance gas exposes Hagedorn states as a tool to understand hadronization.

  7. Fast measurement of automotive headlamps based on high dynamic range imaging.

    PubMed

    Wu, Hsien-Huang P; Lee, Yi-Ping; Chang, Shih-Hsin

    2012-10-01

    The headlamp of the automobile is a very important device for the safety of driving in the dark. Therefore, the distribution of the light designed to provide forward and lateral illumination needs to meet the requirements of various regulations. Traditional measurement of the distribution has been based on a point-by-point approach using a goniophotometer. In this paper, an imaging photometer is developed by combining a regular digital camera and a high dynamic range imaging technique to achieve faster and more complete measurement of the entire distribution. The experimental results indicate that errors of the measurements are within 10% of the true values, which is better than the 20% requirements of the industry.

  8. 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

  9. 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.

  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. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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).

  17. 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. PMID:26739104

  18. Intracellular chromium reduction.

    PubMed

    Arslan, P; Beltrame, M; Tomasi, A

    1987-10-22

    Two steps are involved in the uptake of Cr(VI): (1) the diffusion of the anion CrO4(2-) through a facilitated transport system, presumably the non-specific anion carrier and (2) the intracellular reduction of Cr(VI) to Cr(III). The intracellular reduction of Cr(VI), keeping the cytoplasmic concentration of Cr(VI) low, facilitates accumulation of chromate from extracellular medium into the cell. In the present paper, a direct demonstration of intracellular chromium reduction is provided by means of electron paramagnetic (spin) resonance (EPR) spectroscopy. Incubation of metabolically active rat thymocytes with chromate originates a signal which can be attributed to a paramagnetic species of chromium, Cr(V) or Cr(III). The EPR signal is originated by intracellular reduction of chromium since: (1) it is observed only when cells are incubated with chromate, (2) it is present even after extensive washings of the cells in a chromium-free medium; (3) it is abolished when cells are incubated with drugs able to reduce the glutathione pool, i.e., diethylmaleate or phorone; and (4) it is abolished when cells are incubated in the presence of a specific inhibitor of the anion carrier, 4-acetamido-4'-isothiocyanatostilbene-2-2'-disulfonic acid. PMID:2820507

  19. Chloride Regulation: A Dynamic Equilibrium Crucial for Synaptic Inhibition.

    PubMed

    Doyon, Nicolas; Vinay, Laurent; Prescott, Steven A; De Koninck, Yves

    2016-03-16

    Fast synaptic inhibition relies on tight regulation of intracellular Cl(-). Chloride dysregulation is implicated in several neurological and psychiatric disorders. Beyond mere disinhibition, the consequences of Cl(-) dysregulation are multifaceted and best understood in terms of a dynamical system involving complex interactions between multiple processes operating on many spatiotemporal scales. This dynamical perspective helps explain many unintuitive manifestations of Cl(-) dysregulation. Here we discuss how taking into account dynamical regulation of intracellular Cl(-) is important for understanding how synaptic inhibition fails, how to best detect that failure, why Cl(-) regulation is energetically so expensive, and the overall consequences for therapeutics. PMID:26985723

  20. Chloride Regulation: A Dynamic Equilibrium Crucial for Synaptic Inhibition.

    PubMed

    Doyon, Nicolas; Vinay, Laurent; Prescott, Steven A; De Koninck, Yves

    2016-03-16

    Fast synaptic inhibition relies on tight regulation of intracellular Cl(-). Chloride dysregulation is implicated in several neurological and psychiatric disorders. Beyond mere disinhibition, the consequences of Cl(-) dysregulation are multifaceted and best understood in terms of a dynamical system involving complex interactions between multiple processes operating on many spatiotemporal scales. This dynamical perspective helps explain many unintuitive manifestations of Cl(-) dysregulation. Here we discuss how taking into account dynamical regulation of intracellular Cl(-) is important for understanding how synaptic inhibition fails, how to best detect that failure, why Cl(-) regulation is energetically so expensive, and the overall consequences for therapeutics.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

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

    NASA Astrophysics Data System (ADS)

    Harrison, Aaron W.; Ryazanov, Mikhail; Sullivan, Erin N.; Neumark, Daniel M.

    2016-07-01

    The photodissociation dynamics of the methyl perthiyl radical (CH3SS) have been investigated using fast-beam coincidence translational spectroscopy. Methyl perthiyl radicals were produced by photodetachment of the CH3SS- anion followed by photodissociation at 248 nm (5.0 eV) and 193 nm (6.4 eV). Photofragment mass distributions and translational energy distributions were measured at each dissociation wavelength. Experimental results show S atom loss as the dominant (96%) dissociation channel at 248 nm with a near parallel, anisotropic angular distribution and translational energy peaking near the maximal energy available to ground state CH3S and S fragments, indicating that the dissociation occurs along a repulsive excited state. At 193 nm, S atom loss remains the major fragmentation channel, although S2 loss becomes more competitive and constitutes 32% of the fragmentation. The translational energy distributions for both channels are very broad at this wavelength, suggesting the formation of the S2 and S atom products in several excited electronic states.

  8. Micelle dynamic simulation and physicochemical characterization of biorelevant media to reflect gastrointestinal environment in fasted and fed states.

    PubMed

    Xie, XiaoYu; Cardot, Jean-Michel; Garrait, Ghislain; Thery, Vincent; El-Hajji, Mohamed; Beyssac, Eric

    2014-10-01

    The characterization of biorelevant media simulating the upper part of the gastrointestinal tract in the fasted and fed states was investigated by classical determination of physicochemical parameters such as pH, osmolality, surface tension and results were compared to in vivo physiological data. Incorporation of fatty material, in order to better simulate the influence of high fat meal was also performed. Stability and characterization of this medium was studied and compared to classical FeSSIF. Micelle characterization and computer dynamic simulation were performed in order to understand the interaction between lecithin and taurocholate and possible interactions between mixed micelle and drugs. The addition of NaTc, lecithin, and/or fatty materials has no influence on pH and osmolality, whereas the presence of fatty material modifies the surface tension. Values of FaSSIF and FeSSIF are in accordance with in vivo parameters and the presence of micelles can simulate the gastrointestinal environment. Modelization of micelles by computer simulation led to a model of mixed micelles in which structures of NaTc interact either by their hydrophilic or hydrophobic phase to give a bilayer stable model in which the lecithin molecule can insert its long carbon chain. The micelle structure is stable and can enhance dissolution of hydrophobic molecules by hydrophobic interaction with the numerous hydrophobic spaces available in the multilayer hydrophilic/hydrophobic layer.

  9. Modeling radiation belt electron acceleration by ULF fast mode waves, launched by solar wind dynamic pressure fluctuations

    NASA Astrophysics Data System (ADS)

    Degeling, A. W.; Rankin, R.; Zong, Q.-G.

    2014-11-01

    We investigate the magnetospheric MHD and energetic electron response to a Storm Sudden Commencement (SSC) and subsequent magnetopause buffeting, focusing on an interval following an SSC event on 25 November 2001. We find that the electron flux signatures observed by LANL, Cluster, and GOES spacecraft during this event can largely be reproduced using an advective kinetic model for electron phase space density, using externally prescribed electromagnetic field inputs, (herein described as a "test-kinetic model") with electromagnetic field inputs provided by a 2-D linear ideal MHD model for ULF waves. In particular, we find modulations in electron flux phase shifted by 90° from the local azimuthal ULF wave electric field (Eφ) and a net enhancement in electron flux after 1.5 h for energies between 500 keV and 1.5 MeV near geosynchronous orbit. We also demonstrate that electrons in this energy range satisfy the drift resonance condition for the ULF waves produced by the MHD model. This confirms the conclusions reached by Tan et al. (2011), that the energization process in this case is dominated by drift-resonant interactions between electrons and MHD fast mode waves, produced by fluctuations in solar wind dynamic pressure.

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

    PubMed

    Harrison, Aaron W; Ryazanov, Mikhail; Sullivan, Erin N; Neumark, Daniel M

    2016-07-14

    The photodissociation dynamics of the methyl perthiyl radical (CH3SS) have been investigated using fast-beam coincidence translational spectroscopy. Methyl perthiyl radicals were produced by photodetachment of the CH3SS(-) anion followed by photodissociation at 248 nm (5.0 eV) and 193 nm (6.4 eV). Photofragment mass distributions and translational energy distributions were measured at each dissociation wavelength. Experimental results show S atom loss as the dominant (96%) dissociation channel at 248 nm with a near parallel, anisotropic angular distribution and translational energy peaking near the maximal energy available to ground state CH3S and S fragments, indicating that the dissociation occurs along a repulsive excited state. At 193 nm, S atom loss remains the major fragmentation channel, although S2 loss becomes more competitive and constitutes 32% of the fragmentation. The translational energy distributions for both channels are very broad at this wavelength, suggesting the formation of the S2 and S atom products in several excited electronic states.

  12. CO2 induced acute respiratory acidosis and brain tissue intracellular pH: a 31P NMR study in swine.

    PubMed

    Martoft, L; Stødkilde-Jørgensen, H; Forslid, A; Pedersen, H D; Jørgensen, P F

    2003-07-01

    High concentration carbon dioxide (CO(2)) is used to promote pre-slaughter anaesthesia in swine and poultry, as well as short-lasting surgical anaesthesia and euthanasia in laboratory animals. Questions related to animal welfare have been raised, as CO(2) anaesthesia does not set in momentarily. Carbon dioxide promotes anaesthesia by lowering the intracellular pH in the brain cells, but the dynamics of the changes in response to a high concentration of CO(2) is not known. Based on (31)P NMR spectroscopy, we describe CO(2)-induced changes in intracellular pH in the brains of five pigs inhaling 90% CO(2) in ambient air for a period of 60 s, and compare the results to changes in arterial blood pH, P(CO2), O(2) saturation and HCO(3)(-) concentration. The intracellular pH paralleled the arterial pH and P(CO2) during inhalation of CO(2); and it is suggested that the acute reaction to CO(2) inhalation mainly reflects respiratory acidosis, and not metabolic regulation as for example transmembrane fluxes of H(+)/HCO(3)(-). The intracellular pH decreased to approximately 6.7 within the 60 s inhalation period, and the situation was metabolically reversible after the end of CO(2) inhalation. The fast decrease in intracellular pH supports the conclusion that high concentration CO(2) leads to anaesthesia soon after the start of inhalation. PMID:12869287

  13. 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. PMID:25175760

  14. Analysis of Intracellular Glucose at Single Cells Using Electrochemiluminescence Imaging.

    PubMed

    Xu, Jingjing; Huang, Peiyuan; Qin, Yu; Jiang, Dechen; Chen, Hong-Yuan

    2016-05-01

    Here, luminol electrochemiluminescence was first applied to analyze intracellular molecules, such as glucose, at single cells. The individual cells were retained in cell-sized microwells on a gold coated indium tin oxide (ITO) slide, which were treated with luminol, triton X-100, and glucose oxidase simultaneously. The broken cellular membrane in the presence of triton X-100 released intracellular glucose into the microwell and reacted with glucose oxidase to generate hydrogen peroxide, which induced luminol luminescence under positive potential. To achieve fast analysis, the luminescences from 64 individual cells on one ITO slide were imaged in 60 s using a charge-coupled device (CCD). More luminescence was observed at all the microwells after the introduction of triton X-100 and glucose oxidase suggested that intracellular glucose was detected at single cells. The starvation of cells to decrease intracellular glucose produced less luminescence, which confirmed that our luminescence intensity was correlated with the concentration of intracellular glucose. Large deviations in glucose concentration at observed single cells revealed high cellular heterogeneity in intracellular glucose for the first time. This developed electrochemiluminescence assay will be potentially applied for fast analysis of more intracellular molecules in single cells to elucidate cellular heterogeneity. PMID:27094779

  15. 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.

  16. 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.

  17. Use of the Dynamic Gastric Model as a tool for investigating fed and fasted sensitivities of low polymer content hydrophilic matrix formulations.

    PubMed

    Mason, Laura M; Chessa, Simona; Huatan, Hiep; Storey, David E; Gupta, Pranav; Burley, Jonathan; Melia, Colin D

    2016-08-20

    The Dynamic Gastric Model (DGM) is an in-vitro system which aims to closely replicate the complex mixing, dynamic biochemical release and emptying patterns of the human stomach. In this study, the DGM was used to understand how the polymer content of hydrophilic matrices influences drug release in fasted and fed dissolution environments. Matrices containing a soluble model drug (caffeine) and between 10 and 30% HPMC 2208 (METHOCEL(®) K4M CR) were studied in the DGM under simulated fasted and fed conditions. The results were compared with compendial USP I and USP II dissolution tests. The USP I and II tests clearly discriminated between formulations containing different polymer levels, whereas the fasted DGM test bracketed drug release profiles into three groups and was not able to distinguish between some different formulations. DGM tests in the fed state showed that drug release was substantially influenced by the presence of a high fat meal. Under these conditions, there was a delay before initial drug release, and differences between matrices with different polymer contents were no longer clear. Matrices containing the typical amount of HPMC polymer (30% w/w) exhibited similar release rates under fed and fasted DGM conditions, but matrices with lower polymer contents exhibited more rapid drug release in the fasted state. In both the fasted and fed states erosion mechanisms appeared to dominate drug release in the DGM: most likely a consequence of the changing, cylindrical forces exerted during simulated antral cycling. This is in contrast to the USP tests in which diffusion played a significant role in the drug release process. This study is one of the first publications where a series of extended release (ER) formulations have been studied in the DGM. The technique appears to offer a useful tool to explore the potential sensitivity of ER formulations with respect to the gastric environment, especially the presence of food.

  18. Use of the Dynamic Gastric Model as a tool for investigating fed and fasted sensitivities of low polymer content hydrophilic matrix formulations.

    PubMed

    Mason, Laura M; Chessa, Simona; Huatan, Hiep; Storey, David E; Gupta, Pranav; Burley, Jonathan; Melia, Colin D

    2016-08-20

    The Dynamic Gastric Model (DGM) is an in-vitro system which aims to closely replicate the complex mixing, dynamic biochemical release and emptying patterns of the human stomach. In this study, the DGM was used to understand how the polymer content of hydrophilic matrices influences drug release in fasted and fed dissolution environments. Matrices containing a soluble model drug (caffeine) and between 10 and 30% HPMC 2208 (METHOCEL(®) K4M CR) were studied in the DGM under simulated fasted and fed conditions. The results were compared with compendial USP I and USP II dissolution tests. The USP I and II tests clearly discriminated between formulations containing different polymer levels, whereas the fasted DGM test bracketed drug release profiles into three groups and was not able to distinguish between some different formulations. DGM tests in the fed state showed that drug release was substantially influenced by the presence of a high fat meal. Under these conditions, there was a delay before initial drug release, and differences between matrices with different polymer contents were no longer clear. Matrices containing the typical amount of HPMC polymer (30% w/w) exhibited similar release rates under fed and fasted DGM conditions, but matrices with lower polymer contents exhibited more rapid drug release in the fasted state. In both the fasted and fed states erosion mechanisms appeared to dominate drug release in the DGM: most likely a consequence of the changing, cylindrical forces exerted during simulated antral cycling. This is in contrast to the USP tests in which diffusion played a significant role in the drug release process. This study is one of the first publications where a series of extended release (ER) formulations have been studied in the DGM. The technique appears to offer a useful tool to explore the potential sensitivity of ER formulations with respect to the gastric environment, especially the presence of food. PMID:27311354

  19. Compartmental analysis of technetium-99m-teboroxime kinetics employing fast dynamic SPECT at rest and stress

    SciTech Connect

    Chiao, P.C.; Ficaro, E.P.; Dayaniki, F.

    1994-08-01

    The authors have examined the feasibility of compartmental analysis of {sup 99m}Tc-teboroxime kinetics in measuring physiological changes in response to adenosine-induced coronary vasodilation. To evaluate the effect of tracer recirculation on {sup 99m}Tc-teboroxime kinetics in the myocardium, they also compared compartmental analysis with washout analysis (monoexponertial fitting), which does not account for this effect. Eight healthy male volunteers were imaged using fast dynamic SPECT protocols (5 sec per tomographic image) at rest and during adenosine infusion. A two-compartment model was used and compartmental parameters K1 and k2 (characterizing the diffusion of {sup 99m}Tc-teboroxime from the blood to the myocardium and from the myocardium to the blood, respectively) were fitted from myocardial time-activity curves and left ventricular input functions. Both K1 and washout estimates for the whole left ventricular myocardium changed significantly in response to coronary vasodilation. Mean stress-to-rest (S/R) ratios were almost two times higher for K1 (S/R = 2.7 {plus_minus} 1.1) than for washout estimates (S/R = 1.5 {plus_minus} 0.3). Estimation of K1 for all local regions, except the septal wall, is feasible because variations in K1 estimates for all local regions, except the septum during stress, are comparable with those for the global region. The authors conclude that quantitative compartmental analysis of {sup 99m}Tc-teboroxime kinetics provides a sensitive indicator for changes in response to adenosine-induced coronary vasodilation. 39 refs., 7 figs., 1 tab.

  20. 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. 

  1. Dynamics of dusty radiation-pressure-driven shells and clouds: fast outflows from galaxies, star clusters, massive stars, and AGN

    NASA Astrophysics Data System (ADS)

    Thompson, Todd A.; Fabian, Andrew C.; Quataert, Eliot; Murray, Norman

    2015-05-01

    It is typically assumed that radiation-pressure-driven winds are accelerated to an asymptotic velocity of v∞ ≃ vesc, where vesc is the escape velocity from the central source. We note that this is not the case for dusty shells and clouds. Instead, if the shell or cloud is initially optically thick to the UV emission from the source of luminosity L, then there is a significant boost in v∞ that reflects the integral of the momentum absorbed as it is accelerated. For shells reaching a generalized Eddington limit, we show that v∞ ≃ (4RUVL/Mshc)1/2, in both point-mass and isothermal-sphere potentials, where RUV is the radius where the shell becomes optically thin to UV photons, and Msh is the mass of the shell. The asymptotic velocity significantly exceeds vesc for typical parameters, and can explain the ˜1000-2000 km s-1 outflows observed from rapidly star-forming galaxies and active galactic nuclei (AGN) if the surrounding halo has low gas density. Similarly fast outflows from massive stars can be accelerated on ˜few-103 yr time-scales. These results carry over to clouds that subtend only a small fraction of the solid angle from the source of radiation and that expand as a consequence of their internal sound speed. We further consider the dynamics of shells that sweep up a dense circumstellar or circumgalactic medium. We calculate the `momentum ratio' dot{M} v/(L/c) in the shell limit and show that it can only significantly exceed ˜2 if the effective optical depth of the shell to re-radiated far-infrared photons is much larger than unity. We discuss simple prescriptions for the properties of galactic outflows for use in large-scale cosmological simulations. We also briefly discuss applications to the dusty ejection episodes of massive stars, the disruption of giant molecular clouds, and AGN.

  2. 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

  3. Determination of intracellular nitrate.

    PubMed Central

    Romero, J M; Lara, C; Guerrero, M G

    1989-01-01

    A sensitive procedure has been developed for the determination of intracellular nitrate. The method includes: (i) preparation of cell lysates in 2 M-H3PO4 after separation of cells from the outer medium by rapid centrifugation through a layer of silicone oil, and (ii) subsequent nitrate analysis by ion-exchange h.p.l.c. with, as mobile phase, a solution containing 50 mM-H3PO4 and 2% (v/v) tetrahydrofuran, adjusted to pH 1.9 with NaOH. The determination of nitrate is subjected to interference by chloride and sulphate when present in the samples at high concentrations. Nitrite also interferes, but it is easily eliminated by treatment of the samples with sulphamic acid. The method has been successfully applied to the study of nitrate transport in the unicellular cyanobacterium Anacystis nidulans. PMID:2497740

  4. 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

  5. A Fast Multipole Method and a Metropolis Method for Coarse-grained Brownian Dynamics Simulations of a DNA with Hydrodynamic Interactions

    NASA Astrophysics Data System (ADS)

    Fu, Szu-Pei; Young, Yuan-Nan; Jiang, Shidong

    2014-11-01

    The coarse-grained molecular dynamics (MD) or Brownian dynamics (BD) simulation is a particle-based approach that has been applied to a wide range of biological problems that involve interaction with water molecules. The simulations are often numerically expensive for exploring long-time dynamics over meso-scales due to the amount of water molecules needed for capturing the non-local hydrodynamic interactions (HIs). In this paper a fast multipole method for computing the HIs and a metropolis method for molecular dynamics are validated by comparing against both experiments and simulations of a single DNA molecule in linear flow. In addition, it is shown that the Metropolis integration scheme for self-adjoint diffusions can be used to expedite the time it takes to prepare the initial configuration of the macromolecule for the BD simulations. Further numerical tests show that the fast multipole method scales linearly to the total number N of beads for the long-chain molecule when N >~ O (103) while other numerical algorithms scale to O (N2) (at least). Y.-N. Young acknowledges support from NSF under Grant DMS-1222550.

  6. How Does the Ca(2+)-paradox Injury Induce Contracture in the Heart?-A Combined Study of the Intracellular Ca(2+) Dynamics and Cell Structures in Perfused Rat Hearts.

    PubMed

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

    2015-01-01

    The calcium (Ca(2+))-paradox injury of the heart, induced by restoration of extracellular Ca(2+) after its short-term depletion, is known to provoke cardiomyocyte contracture. However, undetermined is how the Ca(2+)-paradox provokes such a distinctive presentation of myocytes in the heart. To address this, we imaged sequential intracellular Ca(2+) dynamics and concomitant structures of the subepicardial ventricular myocytes in fluo3-loaded, Langendorff-perfused rat hearts produced by the Ca(2+) paradox. Under rapid-scanning confocal microscopy, repletion of Ca(2+) following its depletion produced high-frequency Ca(2+) waves in individual myocytes with asynchronous localized contractions, resulting in contracture within 10 min. Such alterations of myocytes were attenuated by 5-mM NiCl2, but not by verapamil, SEA0400, or combination of ryanodine and thapsigargin, indicating a contribution of non-specific transmembrane Ca(2+) influx in the injury. However, saponin-induced membrane permeabilization of Ca(2+) showed no apparent contracture despite the emergence of high-frequency Ca(2+) waves, indicating an essential role of myocyte-myocyte and myocyte-extracellular matrix (ECM) mechanical connections in the Ca(2+) paradox. In immunohistochemistry Ca(2+) depletion produced separation of the intercalated disc that expresses cadherin and dissipation of β-dystroglycan located along the sarcolemma. Taken together, along with the trans-sarcolemmal Ca(2+) influx, disruption of cell-cell and cell-ECM connections is essential for contracture in the Ca(2+)-paradox injury.

  7. Dual responsive nanogels for intracellular doxorubicin delivery.

    PubMed

    Asadi, Hamed; Khoee, Sepideh

    2016-09-10

    Nanosized polymeric delivery systems that encapsulate drug molecules and release them in response to a specific intracellular stimulus are of promising interest for cancer therapy. Here, we demonstrated a simple and fast synthetic protocol of redox-responsive nanogels with high drug encapsulation efficiency and stability. The prepared nanogels displayed narrow size distributions and versatility of surface modification. The polymer precursor of these nanogels is based on a random copolymer that contains oligoethyleneglycol (OEG) and pyridyldisulfide (PDS) units as side-chain functionalities. The nanogels were prepared through a lock-in strategy in aqueous media via self cross-linking of PDS groups. By changing polymer concentration, we could control the size of nanogels in range of 80-115nm. The formed nanogels presented high doxorubicin (DOX) encapsulation efficiency (70% (w/w)) and displayed pH and redox-controlled drug release triggered by conditions mimicking the reducible intracellular environment. The nanogels displayed an excellent cytocompatibility and were effectively endocytosed by A2780CP ovarian cancer cells, which make them promising nanomaterials for the efficient intracellular delivery of anticancer drugs. PMID:27444549

  8. Development and validation of a dynamic vapor sorption-fast gas chromatography-flame ionization detection method for rapid analysis of volatile release from glassy matrices.

    PubMed

    Bohn, Dawn M; Cadwallader, Keith R; Schmidt, Shelly J

    2005-04-20

    Historically, saturated salt solutions in desiccators have been used to investigate the effects of increasing relative humidity and temperature on the volatile retention efficiency of amorphous glasses. Obtaining data using desiccators is a static process that gives the researcher discrete data points with which to draw conclusions. Dynamic vapor sorption (DVS; SMS, London, U.K.) is a humidification system that creates specific relative humidity and temperature environments within a chamber that contains the material being investigated. This study had two specific aims: (1) to develop a DVS-fast GC-FID method that dynamically evaluates the effects of humidification and temperature increases on volatile release from amorphous carbohydrate glasses and (2) to evaluate the validity of the DVS-fast GC-FID method. Artificial cherry Durarome (Firmenich, Plainsboro, NJ) was used as the model system. The DVS-fast GC-FID method proved to be an innovative, accurate, and precise technique that can be used to conduct humidification/temperature-volatile release studies. PMID:15826072

  9. 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

  10. Mechanisms of intracellular ice formation.

    PubMed Central

    Muldrew, K; McGann, L E

    1990-01-01

    The phenomenon of intracellular freezing in cells was investigated by designing experiments with cultured mouse fibroblasts on a cryomicroscope to critically assess the current hypotheses describing the genesis of intracellular ice: (a) intracellular freezing is a result of critical undercooling; (b) the cytoplasm is nucleated through aqueous pores in the plasma membrane; and (c) intracellular freezing is a result of membrane damage caused by electrical transients at the ice interface. The experimental data did not support any of these theories, but was consistent with the hypothesis that the plasma membrane is damaged at a critical gradient in osmotic pressure across the membrane, and intracellular freezing occurs as a result of this damage. An implication of this hypothesis is that mathematical models can be used to design protocols to avoid damaging gradients in osmotic pressure, allowing new approaches to the preservation of cells, tissues, and organs by rapid cooling. PMID:2306499

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

    PubMed Central

    2015-01-01

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

  12. Fast adaptive OFDM-PON over single fiber loopback transmission using dynamic rate adaptation-based algorithm for channel performance improvement

    NASA Astrophysics Data System (ADS)

    Kartiwa, Iwa; Jung, Sang-Min; Hong, Moon-Ki; Han, Sang-Kook

    2014-03-01

    In this paper, we propose a novel fast adaptive approach that was applied to an OFDM-PON 20-km single fiber loopback transmission system to improve channel performance in term of stabilized BER below 2 × 10-3 and higher throughput beyond 10 Gb/s. The upstream transmission is performed through light source-seeded modulation using 1-GHz RSOA at the ONU. Experimental results indicated that the dynamic rate adaptation algorithm based on greedy Levin-Campello could be an effective solution to mitigate channel instability and data rate degradation caused by the Rayleigh back scattering effect and inefficient resource subcarrier allocation.

  13. Post-scram Liquid Metal cooled Fast Breeder Reactor (LMFBR) heat transport system dynamics and steam generator control: Figures

    NASA Astrophysics Data System (ADS)

    Brukx, J. F. L. M.

    1982-06-01

    Dynamic modeling of LMFBR heat transport system is discussed. Uncontrolled transient behavior of individual components and of the integrated heat transport system are considered. For each component, results showing specific dynamic features of the component and/or model capability were generated. Controlled dynamic behavior for alternative steam generator control systems during forced and natural sodium coolant circulation was analyzed. Combined free and forced convection of laminar and turbulent vertical pipe flow of liquid metals was investigated.

  14. 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

  15. Ultra-fast Microwave Synthesis of ZnO Nanowires and their Dynamic Response Toward Hydrogen Gas.

    PubMed

    Qurashi, Ahsanulhaq; Tabet, N; Faiz, M; Yamzaki, Toshinari

    2009-04-25

    Ultra-fast and large-quantity (grams) synthesis of one-dimensional ZnO nanowires has been carried out by a novel microwave-assisted method. High purity Zinc (Zn) metal was used as source material and placed on microwave absorber. The evaporation/oxidation process occurs under exposure to microwave in less than 100 s. Field effect scanning electron microscopy analysis reveals the formation of high aspect-ratio and high density ZnO nanowires with diameter ranging from 70 to 80 nm. Comprehensive structural analysis showed that these ZnO nanowires are single crystal in nature with excellent crystal quality. The gas sensor made of these ZnO nanowires exhibited excellent sensitivity, fast response, and good reproducibility. Furthermore, the method can be extended for the synthesis of other oxide nanowires that will be the building block of future nanoscale devices.

  16. A fast key generation method based on dynamic biometrics to secure wireless body sensor networks for p-health.

    PubMed

    Zhang, G H; Poon, Carmen C Y; Zhang, Y T

    2010-01-01

    Body sensor networks (BSNs) have emerged as a new technology for healthcare applications, but the security of communication in BSNs remains a formidable challenge yet to be resolved. The paper discusses the typical attacks faced by BSNs and proposes a fast biometric based approach to generate keys for ensuing confidentiality and authentication in BSN communications. The approach was tested on 900 segments of electrocardiogram. Each segment was 4 seconds long and used to generate a 128-bit key. The results of the study found that entropy of 96% of the keys were above 0.95 and 99% of the hamming distances calculated from any two keys were above 50 bits. Based on the randomness and distinctiveness of these keys, it is concluded that the fast biometric based approach has great potential to be used to secure communication in BSNs for health applications. PMID:21096428

  17. A fast key generation method based on dynamic biometrics to secure wireless body sensor networks for p-health.

    PubMed

    Zhang, G H; Poon, Carmen C Y; Zhang, Y T

    2010-01-01

    Body sensor networks (BSNs) have emerged as a new technology for healthcare applications, but the security of communication in BSNs remains a formidable challenge yet to be resolved. The paper discusses the typical attacks faced by BSNs and proposes a fast biometric based approach to generate keys for ensuing confidentiality and authentication in BSN communications. The approach was tested on 900 segments of electrocardiogram. Each segment was 4 seconds long and used to generate a 128-bit key. The results of the study found that entropy of 96% of the keys were above 0.95 and 99% of the hamming distances calculated from any two keys were above 50 bits. Based on the randomness and distinctiveness of these keys, it is concluded that the fast biometric based approach has great potential to be used to secure communication in BSNs for health applications.

  18. FAST User Guide

    NASA Technical Reports Server (NTRS)

    Walatka, Pamela P.; Clucas, Jean; McCabe, R. Kevin; Plessel, Todd; Potter, R.; Cooper, D. M. (Technical Monitor)

    1994-01-01

    The Flow Analysis Software Toolkit, FAST, is a software environment for visualizing data. FAST is a collection of separate programs (modules) that run simultaneously and allow the user to examine the results of numerical and experimental simulations. The user can load data files, perform calculations on the data, visualize the results of these calculations, construct scenes of 3D graphical objects, and plot, animate and record the scenes. Computational Fluid Dynamics (CFD) visualization is the primary intended use of FAST, but FAST can also assist in the analysis of other types of data. FAST combines the capabilities of such programs as PLOT3D, RIP, SURF, and GAS into one environment with modules that share data. Sharing data between modules eliminates the drudgery of transferring data between programs. All the modules in the FAST environment have a consistent, highly interactive graphical user interface. Most commands are entered by pointing and'clicking. The modular construction of FAST makes it flexible and extensible. The environment can be custom configured and new modules can be developed and added as needed. The following modules have been developed for FAST: VIEWER, FILE IO, CALCULATOR, SURFER, TOPOLOGY, PLOTTER, TITLER, TRACER, ARCGRAPH, GQ, SURFERU, SHOTET, and ISOLEVU. A utility is also included to make the inclusion of user defined modules in the FAST environment easy. The VIEWER module is the central control for the FAST environment. From VIEWER, the user can-change object attributes, interactively position objects in three-dimensional space, define and save scenes, create animations, spawn new FAST modules, add additional view windows, and save and execute command scripts. The FAST User Guide uses text and FAST MAPS (graphical representations of the entire user interface) to guide the user through the use of FAST. Chapters include: Maps, Overview, Tips, Getting Started Tutorial, a separate chapter for each module, file formats, and system

  19. 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.

  20. Neural dynamics in a model of the thalamocortical system. I. Layers, loops and the emergence of fast synchronous rhythms.

    PubMed

    Lumer, E D; Edelman, G M; Tononi, G

    1997-01-01

    A large-scale computer model was constructed to gain insight into the structural basis for the generation of fast synchronous rhythms (20-60 Hz) in the thalamocortical system. The model consisted of 65,000 spiking neurons organized topographically to represent sectors of a primary and secondary area of mammalian visual cortex, and two associated regions of the dorsal thalamus and the thalamic reticular nucleus. Cortical neurons, both excitatory and inhibitory, were organized in supragranular layers, infraganular layers and layer IV. Reciprocal intra- and interlaminar, interareal, thalamocortical, corticothalamic and thalamoreticular connections were set up based on known anatomical constraints. Simulations of neuronal responses to visual input revealed sporadic epochs of synchronous oscillations involving all levels of the model, similar to the fast rhythms recorded in vivo. By systematically modifying physiological and structural parameters in the model, specific network properties were found to play a major role in the generation of this rhythmic activity. For example, fast synchronous rhythms could be sustained autonomously by lateral and interlaminar interactions within and among local cortical circuits. In addition, these oscillations were propagated to the thalamus and amplified by corticothalamocortical loops, including the thalamic reticular complex. Finally, synchronous oscillations were differentially affected by lesioning forward and backward interareal connections.

  1. 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.

  2. Intracellular structure and nucleocytoplasmic transport.

    PubMed

    Agutter, P S

    1995-01-01

    Intracellular movement of any solute or particle accords with one of two general schemes: either it takes place predominantly in the solution phase or it occurs by dynamic interactions with solid-state structures. If nucleocytoplasmic exchanges of macromolecules and complexes are predominantly solution-phase processes, i.e., if the former ("diffusionist") perspective applies, then the only significant structures in nucleocytoplasmic transport are the pore complexes. However, if such exchanges accord with the latter ("solid-state") perspective, then the roles of the nucleoskeleton and cytoskeleton in nucleocytoplasmic transport are potentially, at least, as important as that of the pore complexes. The role of the nucleoskeleton in mRNA transport is more difficult to evaluate than that of the cytoskeleton because it is less well characterized, and current evidence does not exclude either perspective. However, the balance of evidence favors a solid-state scheme. It is argued that ribosomal subunits are also more likely to migrate by a solid-state rather than a diffusionist mechanism, though the opposite is true of proteins and tRNAs. Moreover, recent data on the effects of viral proteins on intranuclear RNA processing and migration accord with the solid-state perspective. In view of this balance of evidence, three possible solid-state mechanisms for nucleocytoplasmic mRNA transport are described and evaluated. The explanatory advantage of solid-state models is contrasted with the heuristic advantage of diffusion theory, but it is argued that diffusion theory itself, even aided by modern computational techniques and numerical and graphical approaches, cannot account for data describing the movements of materials within the cell. Therefore, the mechanisms envisaged in a diffusionist perspective cannot be confined to diffusion alone, but must include other processes such as bulk fluid flow.

  3. 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...

  4. 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’.

  5. 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’.

  6. Extracellular Matrix Stiffness and Architecture Govern Intracellular Rheology in Cancer

    PubMed Central

    Baker, Erin L.; Bonnecaze, Roger T.; Zaman, Muhammad H.

    2009-01-01

    Abstract Little is known about the complex interplay between the extracellular mechanical environment and the mechanical properties that characterize the dynamic intracellular environment. To elucidate this relationship in cancer, we probe the intracellular environment using particle-tracking microrheology. In three-dimensional (3D) matrices, intracellular effective creep compliance of prostate cancer cells is shown to increase with increasing extracellular matrix (ECM) stiffness, whereas modulating ECM stiffness does not significantly affect the intracellular mechanical state when cells are attached to two-dimensional (2D) matrices. Switching from 2D to 3D matrices induces an order-of-magnitude shift in intracellular effective creep compliance and apparent elastic modulus. However, for a given matrix stiffness, partial blocking of β1 integrins mitigates the shift in intracellular mechanical state that is invoked by switching from a 2D to 3D matrix architecture. This finding suggests that the increased cell-matrix engagement inherent to a 3D matrix architecture may contribute to differences observed in viscoelastic properties between cells attached to 2D matrices and cells embedded within 3D matrices. In total, our observations show that ECM stiffness and architecture can strongly influence the intracellular mechanical state of cancer cells. PMID:19686648

  7. Post-scram Liquid Metal cooled Fast Breeder Reactor (LMFBR) neat transport system dynamics and steam generator control

    NASA Astrophysics Data System (ADS)

    Brukx, J. F. L. M.

    1982-06-01

    Loop type LMFBR heat transport system dynamics after reactor shutdown and during subsequent decay heat removal are considered with emphasis on steam generator dynamics including the development and evaluation of various post-scram steam generator control systems, and natural circulation of the sodium coolant, including the influence of superimposed free convection on forced convection heat transfer and pressure drop. The normal operating and decay heat removal functions of the overall heat transport system are described.

  8. Live cell imaging of intracellular Salmonella enterica.

    PubMed

    Kehl, Alexander; Hensel, Michael

    2015-01-01

    During the intracellular phase of the pathogenic lifestyle, Salmonella enterica massively alters the endosomal system of its host cells. Two hallmarks are the remodeling of phagosomes into the Salmonella-containing vacuole (SCV) as a replicative niche, and the formation of tubular structures, such as Salmonella-induced filaments (SIFs). To study the dynamics and the fate of these Salmonella-specific compartments, live cell imaging (LCI) is a method of choice. In this chapter, we compare currently used microscopy techniques and focus on considerations and requirements specific for LCI. Detailed protocols for LCI of Salmonella infection with either confocal laser scanning microscopy (CLSM) or spinning disk confocal microscopy (SDCM) are provided.

  9. 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.

  10. Visualization of Cortical Dynamics

    NASA Astrophysics Data System (ADS)

    Grinvald, Amiram

    2003-03-01

    Recent progress in studies of cortical dynamics will be reviewed including the combination of real time optical imaging based on voltage sensitive dyes, single and multi- unit recordings, LFP, intracellular recordings and microstimulation. To image the flow of neuronal activity from one cortical site to the next, in real time, we have used optical imaging based on newly designed voltage sensitive dyes and a Fuji 128x 128 fast camera which we modified. A factor of 20-40 fold improvement in the signal to noise ratio was obtained with the new dye during in vivo imaging experiments. This improvements has facilitates the exploration of cortical dynamics without signal averaging in the millisecond time domain. We confirmed that the voltage sensitive dye signal indeed reflects membrane potential changes in populations of neurons by showing that the time course of the intracellular activity recorded intracellularly from a single neuron was highly correlated in many cases with the optical signal from a small patch of cortex recorded nearby. We showed that the firing of single cortical neurons is not a random process but occurs when the on-going pattern of million of neurons is similar to the functional architecture map which correspond to the tuning properties of that neuron. Chronic optical imaging, combined with electrical recordings and microstimulation, over a long period of times of more than a year, was successfully applied also to the study of higher brain functions in the behaving macaque monkey.

  11. 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.

  12. 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.

  13. Golden-Angle Radial Sparse Parallel MRI: Combination of Compressed Sensing, Parallel Imaging, and Golden-Angle Radial Sampling for Fast and Flexible Dynamic Volumetric MRI

    PubMed Central

    Feng, Li; Grimm, Robert; Block, Kai Tobias; Chandarana, Hersh; Kim, Sungheon; Xu, Jian; Axel, Leon; Sodickson, Daniel K.; Otazo, Ricardo

    2013-01-01

    Purpose To develop a fast and flexible free-breathing dynamic volumetric MRI technique, iterative Golden-angle RAdial Sparse Parallel MRI (iGRASP), that combines compressed sensing, parallel imaging, and golden-angle radial sampling. Methods Radial k-space data are acquired continuously using the golden-angle scheme and sorted into time series by grouping an arbitrary number of consecutive spokes into temporal frames. An iterative reconstruction procedure is then performed on the undersampled time series where joint multicoil sparsity is enforced by applying a total-variation constraint along the temporal dimension. Required coil-sensitivity profiles are obtained from the time-averaged data. Results iGRASP achieved higher acceleration capability than either parallel imaging or coil-by-coil compressed sensing alone. It enabled dynamic volumetric imaging with high spatial and temporal resolution for various clinical applications, including free-breathing dynamic contrast-enhanced imaging in the abdomen of both adult and pediatric patients, and in the breast and neck of adult patients. Conclusion The high performance and flexibility provided by iGRASP can improve clinical studies that require robustness to motion and simultaneous high spatial and temporal resolution. PMID:24142845

  14. A POSSIBLE DETECTION OF A FAST-MODE EXTREME ULTRAVIOLET WAVE ASSOCIATED WITH A MINI CORONAL MASS EJECTION OBSERVED BY THE SOLAR DYNAMICS OBSERVATORY

    SciTech Connect

    Zheng Ruisheng; Jiang Yunchun; Hong Junchao; Yang Jiayan; Bi Yi; Yang Liheng; Yang Dan

    2011-10-01

    'Extreme ultraviolet (EUV) waves' are large-scale wavelike transients often associated with coronal mass ejections (CMEs). In this Letter, we present a possible detection of a fast-mode EUV wave associated with a mini-CME observed by the Solar Dynamics Observatory. On 2010 December 1, a small-scale EUV wave erupted near the disk center associated with a mini-CME, which showed all the low corona manifestations of a typical CME. The CME was triggered by the eruption of a mini-filament, with a typical length of about 30''. Although the eruption was tiny, the wave had the appearance of an almost semicircular front and propagated at a uniform velocity of 220-250 km s{sup -1} with very little angular dependence. The CME lateral expansion was asymmetric with an inclination toward north, and the southern footprints of the CME loops hardly shifted. The lateral expansion resulted in deep long-duration dimmings, showing the CME extent. Comparing the onset and the initial speed of the CME, the wave was likely triggered by the rapid expansion of the CME loops. Our analysis confirms that the small-scale EUV wave is a true wave, interpreted as a fast-mode wave.

  15. Characterization of pressure dynamics in an axisymmetric separating/reattaching flow using fast-responding pressure-sensitive paint

    NASA Astrophysics Data System (ADS)

    Bitter, Martin; Hara, Tatsuya; Hain, Rainer; Yorita, Daisuke; Asai, Keisuke; Kähler, Christian J.

    2012-12-01

    This collaborative work discusses the results of time-resolved pressure-sensitive paint measurements performed on a model of a generic spacecraft under sub- and transonic test conditions. It is shown that optical pressure measurements using an active layer from platinum-porphyrin complexes (PtTFPP) in combination with a polymer-ceramic base layer are able to measure dynamic flow phenomena in the trisonic wind tunnel facility up to sampling rates of 2 kHz. Low amplitude fluctuations in the order of 0.1 kPa were determined by means of this measurement technique. The buffet dynamics, as well as the spatial extent of the recirculation area in the near-wake, compare well with numerical predictions and PIV measurements. Furthermore, characteristic coherent pressure modes on the base were resolved, which were predicted by large-eddy simulations.

  16. An effective shortcut to adiabatic passage for fast quantum state transfer in a cavity quantum electronic dynamics system

    NASA Astrophysics Data System (ADS)

    Lu, Mei; Xia, Yan; Shen, Li-Tuo; Song, Jie

    2014-10-01

    We propose an alternative scheme for constructing a shortcut to implement the quantum state transfer between two three-level atoms founded on the invariant-based inverse engineering in a cavity quantum electronic dynamics (QED) system. Quantum information can be quickly transferred between atoms by taking advantage of the cavity field as a medium. Through our design of the time-dependent laser pulse and atom-cavity coupling, we send atoms through the cavity within a short time interval, which involves the two processes of the invariant dynamics between each atom and the cavity field simultaneously. We redesign a reasonable Gaussian-type wave form in the atom-cavity coupling for a realistic experimental operation. Numerical simulation shows that the target state can be quickly populated with a high fidelity which is robust against both the parameter fluctuations and the dissipation.

  17. Backbone dynamics of the human CC chemokine eotaxin: fast motions, slow motions, and implications for receptor binding.

    PubMed Central

    Crump, M. P.; Spyracopoulos, L.; Lavigne, P.; Kim, K. S.; Clark-lewis, I.; Sykes, B. D.

    1999-01-01

    Eotaxin is a member of the chemokine family of about 40 proteins that induce cell migration. Eotaxin binds the CC chemokine receptor CCR3 that is highly expressed by eosinophils, and it is considered important in the pathology of chronic respiratory disorders such as asthma. The high resolution structure of eotaxin is known. The 74 amino acid protein has two disulfide bridges and shows a typical chemokine fold comprised of a core of three antiparallel beta-strands and an overlying alpha-helix. In this paper, we report the backbone dynamics of eotaxin determined through 15N-T1, T2, and [1H]-15N nuclear Overhauser effect heteronuclear multidimensional NMR experiments. This is the first extensive study of the dynamics of a chemokine derived from 600, 500, and 300 MHz NMR field strengths. From the T1, T2, and NOE relaxation data, parameters that describe the internal motions of eotaxin were derived using the Lipari-Szabo model free analysis. The most ordered regions of the protein correspond to the known secondary structure elements. However, surrounding the core, the regions known to be functionally important in chemokines show a range of motions on varying timescales. These include extensive subnanosecond to picosecond motions in the N-terminus, C-terminus, and the N-loop succeeding the disulfides. Analysis of rotational diffusion anisotropy of eotaxin and chemical exchange terms at multiple fields also allowed the confident identification of slow conformational exchange through the "30s" loop, disulfides, and adjacent residues. In addition, we show that these motions may be attenuated in the dimeric form of a synthetic eotaxin. The structure and dynamical basis for eotaxin receptor binding is discussed in light of the dynamics data. PMID:10548050

  18. Fast dynamic 3D MR spectroscopic imaging with compressed sensing and multiband excitation pulses for hyperpolarized 13C studies.

    PubMed

    Larson, Peder E Z; Hu, Simon; Lustig, Michael; Kerr, Adam B; Nelson, Sarah J; Kurhanewicz, John; Pauly, John M; Vigneron, Daniel B

    2011-03-01

    Hyperpolarized 13C MR spectroscopic imaging can detect not only the uptake of the pre-polarized molecule but also its metabolic products in vivo, thus providing a powerful new method to study cellular metabolism. Imaging the dynamic perfusion and conversion of these metabolites provides additional tissue information but requires methods for efficient hyperpolarization usage and rapid acquisitions. In this work, we have developed a time-resolved 3D MR spectroscopic imaging method for acquiring hyperpolarized 13C data by combining compressed sensing methods for acceleration and multiband excitation pulses to efficiently use the magnetization. This method achieved a 2 sec temporal resolution with full volumetric coverage of a mouse, and metabolites were observed for up to 60 sec following injection of hyperpolarized [1-(13)C]-pyruvate. The compressed sensing acquisition used random phase encode gradient blips to create a novel random undersampling pattern tailored to dynamic MR spectroscopic imaging with sampling incoherency in four (time, frequency, and two spatial) dimensions. The reconstruction was also tailored to dynamic MR spectroscopic imaging by applying a temporal wavelet sparsifying transform to exploit the inherent temporal sparsity. Customized multiband excitation pulses were designed with a lower flip angle for the [1-(13)C]-pyruvate substrate given its higher concentration than its metabolic products ([1-(13)C]-lactate and [1-(13)C]-alanine), thus using less hyperpolarization per excitation. This approach has enabled the monitoring of perfusion and uptake of the pyruvate, and the conversion dynamics to lactate and alanine throughout a volume with high spatial and temporal resolution. PMID:20939089

  19. Fast Dynamic 3D MRSI with Compressed Sensing and Multiband Excitation Pulses for Hyperpolarized 13C Studies

    PubMed Central

    Larson, Peder E. Z.; Hu, Simon; Lustig, Michael; Kerr, Adam B.; Nelson, Sarah J.; Kurhanewicz, John; Pauly, John M.; Vigneron, Daniel B.

    2010-01-01

    Hyperpolarized 13C MRSI can detect not only the uptake of the pre-polarized molecule but also its metabolic products in vivo, thus providing a powerful new method to study cellular metabolism. Imaging the dynamic perfusion and conversion of these metabolites provides additional tissue information but requires methods for efficient hyperpolarization usage and rapid acquisitions. In this work, we have developed a time-resolved 3D MRSI method for acquiring hyperpolarized 13C data by combining compressed sensing methods for acceleration and multiband excitation pulses to efficiently use the magnetization. This method achieved a 2 sec temporal resolution with full volumetric coverage of a mouse, and metabolites were observed for up to 60 sec following injection of hyperpolarized [1-13C]-pyruvate. The compressed sensing acquisition used random phase encode gradient blips to create a novel random undersampling pattern tailored to dynamic MRSI with sampling incoherency in four (time, frequency and two spatial) dimensions. The reconstruction was also tailored to dynamic MRSI by applying a temporal wavelet sparsifying transform in order to exploit the inherent temporal sparsity. Customized multiband excitation pulses were designed with a lower flip angle for the [1-13C]-pyruvate substrate given its higher concentration than its metabolic products ([1-13C]-lactate and [1-13C]-alanine), thus using less hyperpolarization per excitation. This approach has enabled the monitoring of perfusion and uptake of the pyruvate, and the conversion dynamics to lactate and alanine throughout a volume with high spatial and temporal resolution. PMID:20939089

  20. 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.

  1. GRIN lens rod based probe for endoscopic spectral domain optical coherence tomography with fast dynamic focus tracking

    NASA Astrophysics Data System (ADS)

    Xie, Tuqiang; Guo, Shuguang; Chen, Zhongping; Mukai, David; Brenner, Matthew

    2006-04-01

    In this manuscript, a GRIN (gradient index) lens rod based probe for endoscopic spectral domain optical coherence tomography (OCT) with dynamic focus tracking is presented. Current endoscopic OCT systems have a fixed focal plane or working distance. In contrast, the focus of this endoscopic OCT probe can dynamically be adjusted at a high speed (500 mm/s) without changing reference arm length to obtain high quality OCT images for contact or non-contact tissue applications, or for areas of difficult access for probes. The dynamic focusing range of the probe can be from 0 to 7.5 mm without moving the probe itself. The imaging depth is 2.8 mm and the lateral scanning range is up to 2.7 mm or 4.5 mm (determined by the diameter of different GRIN lens rods). Three dimensional imaging can be performed using this system over an area of tissue corresponding to the GRIN lens surface. The experimental results demonstrate that this GRIN lens rod based OCT system can perform a high quality non-contact in vivo imaging. This rigid OCT probe is solid and can be adapted to safely access internal organs, to perform front or side view imaging with an imaging speed of 8 frames per second, with all moving parts proximal to the GRIN lens, and has great potential for use in extremely compact OCT endoscopes for in vivo imaging in both biological research and clinical applications.

  2. Miro1 Regulates Activity-Driven Positioning of Mitochondria within Astrocytic Processes Apposed to Synapses to Regulate Intracellular Calcium Signaling.

    PubMed

    Stephen, Terri-Leigh; Higgs, Nathalie F; Sheehan, David F; Al Awabdh, Sana; López-Doménech, Guillermo; Arancibia-Carcamo, I Lorena; Kittler, Josef T

    2015-12-01

    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 Ca(2+). Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the Ca(2+)-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 Ca(2+) in astrocytic processes. Thus, the regulation of intracellular Ca(2+) signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte Ca(2+) wave propagation, gliotransmission, and ultimately neuronal function. PMID:26631479

  3. 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

  4. 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

  5. Integrative Physiology of Fasting.

    PubMed

    Secor, Stephen M; Carey, Hannah V

    2016-04-01

    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. PMID:27065168

  6. 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 . PMID:27231982

  7. 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

  8. Simultaneous measurement of ciliary beating and intracellular calcium.

    PubMed Central

    Korngreen, A; Priel, Z

    1994-01-01

    A novel system for measuring, simultaneously, ciliary beating and intracellular free calcium is presented. The advantages and dynamic nature of the system are demonstrated by measuring the effects of the calcium ionophore lonomycin and of extracellular ATP on ciliated rabbit trachea. The results are discussed with regard to the ciliary and calcium stimulation. PMID:7919010

  9. Encoding of movement dynamics by Purkinje cell simple spike activity during fast arm movements under resistive and assistive force fields.

    PubMed

    Yamamoto, Kenji; Kawato, Mitsuo; Kotosaka, Shinya; Kitazawa, Shigeru

    2007-02-01

    It is controversial whether simple-spike activity of cerebellar Purkinje cells during arm movements encodes movement kinematics like velocity or dynamics like muscle activities. To examine this issue, we trained monkeys to flex or extend the elbow by 45 degrees in 400 ms under resistive and assistive force fields but without altering kinematics. During the task movements after training, simple-spike discharges were recorded in the intermediate part of the cerebellum in lobules V-VI, and electromyographic activity was recorded from arm muscles. Velocity profiles (kinematics) in the two force fields were almost identical to each other, whereas not only the electromyographic activities (dynamics) but also simple-spike activities in many Purkinje cells differed distinctly depending on the type of force field. Simple-spike activities encoded much larger mutual information with the type of force field than that with the residual small difference in the height of peak velocity. The difference in simple-spike activities averaged over the recorded Purkinje-cells increased approximately 40 ms before the appearance of the difference in electromyographic activities between the two force fields, suggesting that the difference of simple-spike activities could be the origin of the difference of muscle activities. Simple-spike activity of many Purkinje cells correlated with electromyographic activity with a lead of approximately 80 ms, and these neurons had little overlap with another group of neurons the simple-spike activity of which correlated with velocity profiles. These results show that simple-spike activity of at least a group of Purkinje cells in the intermediate part of cerebellar lobules V-VI encodes movement dynamics.

  10. 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.

  11. 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.

  12. Simple and fast calculation of the second-order gradients for globalized dual heuristic dynamic programming in neural networks.

    PubMed

    Fairbank, Michael; Alonso, Eduardo; Prokhorov, Danil

    2012-10-01

    We derive an algorithm to exactly calculate the mixed second-order derivatives of a neural network's output with respect to its input vector and weight vector. This is necessary for the adaptive dynamic programming (ADP) algorithms globalized dual heuristic programming (GDHP) and value-gradient learning. The algorithm calculates the inner product of this second-order matrix with a given fixed vector in a time that is linear in the number of weights in the neural network. We use a "forward accumulation" of the derivative calculations which produces a much more elegant and easy-to-implement solution than has previously been published for this task. In doing so, the algorithm makes GDHP simple to implement and efficient, bridging the gap between the widely used DHP and GDHP ADP methods.

  13. All-atom molecular dynamics simulations of actin-myosin interactions: a comparative study of cardiac α myosin, β myosin, and fast skeletal muscle myosin.

    PubMed

    Li, Minghui; Zheng, Wenjun

    2013-11-26

    Myosins are a superfamily of actin-binding motor proteins with significant variations in kinetic properties (such as actin binding affinity) between different isoforms. It remains unknown how such kinetic variations arise from the structural and dynamic tuning of the actin-myosin interface at the amino acid residue level. To address this key issue, we have employed molecular modeling and simulations to investigate, with atomistic details, the isoform dependence of actin-myosin interactions in the rigor state. By combining electron microscopy-based docking with homology modeling, we have constructed three all-atom models for human cardiac α and β and rabbit fast skeletal muscle myosin in complex with three actin subunits in the rigor state. Starting from these models, we have performed extensive all-atom molecular dynamics (MD) simulations (total of 100 ns per system) and then used the MD trajectories to calculate actin-myosin binding free energies with contributions from both electrostatic and nonpolar forces. Our binding calculations are in good agreement with the experimental finding of isoform-dependent differences in actin binding affinity between these myosin isoforms. Such differences are traced to changes in actin-myosin electrostatic interactions (i.e., hydrogen bonds and salt bridges) that are highly dynamic and involve several flexible actin-binding loops. By partitioning the actin-myosin binding free energy to individual myosin residues, we have also identified key myosin residues involved in the actin-myosin interactions, some of which were previously validated experimentally or implicated in cardiomyopathy mutations, and the rest make promising targets for future mutational experiments. PMID:24224850

  14. 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

  15. Stochastic models of intracellular calcium signals

    NASA Astrophysics Data System (ADS)

    Rüdiger, Sten

    2014-01-01

    Cellular signaling operates in a noisy environment shaped by low molecular concentrations and cellular heterogeneity. For calcium release through intracellular channels-one of the most important cellular signaling mechanisms-feedback by liberated calcium endows fluctuations with critical functions in signal generation and formation. In this review it is first described, under which general conditions the environment makes stochasticity relevant, and which conditions allow approximating or deterministic equations. This analysis provides a framework, in which one can deduce an efficient hybrid description combining stochastic and deterministic evolution laws. Within the hybrid approach, Markov chains model gating of channels, while the concentrations of calcium and calcium binding molecules (buffers) are described by reaction-diffusion equations. The article further focuses on the spatial representation of subcellular calcium domains related to intracellular calcium channels. It presents analysis for single channels and clusters of channels and reviews the effects of buffers on the calcium release. For clustered channels, we discuss the application and validity of coarse-graining as well as approaches based on continuous gating variables (Fokker-Planck and chemical Langevin equations). Comparison with recent experiments substantiates the stochastic and spatial approach, identifies minimal requirements for a realistic modeling, and facilitates an understanding of collective channel behavior. At the end of the review, implications of stochastic and local modeling for the generation and properties of cell-wide release and the integration of calcium dynamics into cellular signaling models are discussed.

  16. 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

  17. 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

  18. Fast range switching of passively scattered proton beams using a modulation wheel and dynamic beam current modulation.

    PubMed

    Sánchez-Parcerisa, D; Pourbaix, J C; Ainsley, C G; Dolney, D; Carabe, A

    2014-04-01

    In proton radiotherapy, the range of particles in the patient body is determined by the energy of the protons. For most systems, the energy selection time is on the order of a few seconds, which becomes a serious obstacle for continuous dose delivery techniques requiring adaptive range modulation. This work analyses the feasibility of using the range modulation wheel, an element in the beamline used to form the spread-out Bragg peak (SOBP), to produce near-instantaneous changes not only in the modulation, but also in the range of the beam. While delivering proton beams in double scattering mode, the beam current can be synchronized with the range modulation wheel rotation by defining a current modulation pattern. Different current modulation patterns were computed from Monte Carlo simulations of our double scattering nozzle to range shift an SOBP of initial range 15 cm by varying degrees of up to ∼9 cm. These patterns were passed to the treatment control system at our institution and the resulting measured depth-dose distributions were analysed in terms of flatness, distal penumbra and relative irradiation time per unit mid-SOBP dose. Suitable SOBPs were obtained in all cases, with the maximum range shift being limited only by the maximum thickness of the wheel. The distal dose fall-off (80% to 20%) of the shifted peaks was broadened to about 1 cm, from the original 0.5 cm, and the predicted overhead in delivery time showed a linear increase with the amount of the shift. By modulating the beam current in clinical scattered proton beams equipped with a modulation wheel, it is possible to dynamically modify the in-patient range of the SOBP without adding any specific hardware or compensators to the beamline. A compromise between sharper distal dose fall-off and lower delivery time can be achieved and is subject to optimization.

  19. Magnetic tweezers for intracellular applications

    NASA Astrophysics Data System (ADS)

    Hosu, Basarab G.; Jakab, Károly; Bánki, Péter; Tóth, Ferenc I.; Forgacs, Gabor

    2003-09-01

    We have designed and constructed a versatile magnetic tweezer primarily for intracellular investigations. The micromanipulator uses only two coils to simultaneously magnetize to saturation micron-size superparamagnetic particles and generate high magnitude constant field gradients over cellular dimensions. The apparatus resembles a miniaturized Faraday balance, an industrial device used to measure magnetic susceptibility. The device operates in both continuous and pulse modes. Due to its compact size, the tweezers can conveniently be mounted on the stage of an inverted microscope and used for intracellular manipulations. A built-in temperature control unit maintains the sample at physiological temperatures. The operation of the tweezers was tested by moving 1.28 μm diameter magnetic beads inside macrophages with forces near 500 pN.

  20. 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

  1. Live cell imaging of duplex siRNA intracellular trafficking

    PubMed Central

    Hirsch, Markus; Helm, Mark

    2015-01-01

    Intracellular distribution of siRNA after in vitro transfection typically depends on lipopolyplexes, which must release the siRNA into the cytosol. Here, the fate of siRNAs was monitored by FRET-based live cell imaging. Subsequent to in situ observation of uptake and release processes, this approach allowed the observation of a number of hitherto uncharacterized intracellular distribution and degradation processes, commencing with a burst of endosomal releases, followed, in some cases, by fast siRNA influx into the nucleus. The continued observation of intact siRNA against a background of free fluorophores resulting from advanced degradation was possible by a specifically developed imaging algorithm, which identified populations of intact siRNA in pixels based on FRET. This proved to be essential in the end point definition of siRNA distribution, which typically featured partially degraded siRNA pools in perinuclear structures. Our results depict the initial 4 h as a critical time window, characterized by fast initial burst release into the cytosol, which lay the foundations for subsequent intracellular distribution of siRNA. Combination with a subsequent slower, but sustained release from endosomal reservoirs may contribute to the efficiency and duration of RNAi, and explain the success of lipopolyplexes in RNAi experiments in cell culture. PMID:25870407

  2. Intracellular calcium channels in protozoa.

    PubMed

    Docampo, Roberto; Moreno, Silvia N J; Plattner, Helmut

    2014-09-15

    Ca(2+)-signaling pathways and intracellular Ca(2+) channels are present in protozoa. Ancient origin of inositol 1,4,5-trisphosphate receptors (IP3Rs) and other intracellular channels predates the divergence of animals and fungi as evidenced by their presence in the choanoflagellate Monosiga brevicollis, the closest known relative to metazoans. The first protozoan IP3R cloned, from the ciliate Paramecium, displays strong sequence similarity to the rat type 3 IP3R. This ciliate has a large number of IP3- and ryanodine(Ry)-like receptors in six subfamilies suggesting the evolutionary adaptation to local requirements for an expanding diversification of vesicle trafficking. IP3Rs have also been functionally characterized in trypanosomatids, where they are essential for growth, differentiation, and establishment of infection. The presence of the mitochondrial calcium uniporter (MCU) in a number of protozoa indicates that mitochondrial regulation of Ca(2+) signaling is also an early appearance in evolution, and contributed to the discovery of the molecular nature of this channel in mammalian cells. There is only sequence evidence for the occurrence of two-pore channels (TPCs), transient receptor potential Ca(2+) channels (TRPCs) and intracellular mechanosensitive Ca(2+)-channels in Paramecium and in parasitic protozoa.

  3. 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.

  4. Intracellular Calcium Channels in Protozoa

    PubMed Central

    Docampo, Roberto; Moreno, Silvia N.J.; Plattner, Helmut

    2014-01-01

    Ca2+-signaling pathways and intracellular Ca2+ channels are present in protozoa. Ancient origin of inositol 1,4,5-trisphosphate receptors (IP3Rs) and other intracellular channels predates the divergence of animals and fungi as evidenced by their presence in the choanoflagellate Monosiga brevicollis, the closest known relative to metazoans. The first protozoan IP3R cloned, from the ciliate Paramecium, displays strong sequence similarity to the rat type 3 IP3R. This ciliate has a large number of IP3- and ryanodine(Ry)-like receptors in 6 subfamilies suggesting the evolutionary adaptation to local requirements for an expanding diversification of vesicle trafficking. IP3Rs have also been functionally characterized in trypanosomatids, where they are essential for growth, differentiation, and establishment of infection. The presence of the mitochondrial calcium uniporter (MCU) in a number of protozoa indicates that mitochondrial regulation of Ca2+ signaling is also an early appearance in evolution, and contributed to the discovery of the molecular nature of this channel in mammalian cells. There is only sequence evidence for the occurrence of two-pore channels (TPCs), transient receptor potential Ca2+ channels (TRPCs) and intracellular mechanosensitive Ca2+-channels in Paramecium and in parasitic protozoa. PMID:24291099

  5. 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

  6. 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

    Staniforth, Michael; Stavros, Vasilios G

    2013-11-01

    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.

  7. Appropriate sampling for intracellular amino acid analysis in five phylogenetically different yeasts.

    PubMed

    Bolten, Christoph J; Wittmann, Christoph

    2008-11-01

    Methanol quenching and fast filtration, the two most common sampling protocols in microbial metabolome analysis, were validated for intracellular amino acid analysis in phylogenetically different yeast strains comprising Saccharomyces cerevisiae, Kluyveromyces marxianus, Pichia pastoris, Schizosaccharomyces pombe and Zygosaccharomyces bailii. With only few exceptions for selected amino acids, all yeasts exhibited negligible metabolite leakage during quenching with 60% cold buffered methanol. Slightly higher leakage was observed with increasing methanol content in the quenching solution. Fast filtration resulted in identical levels for intracellular amino acids in all strains tested. The results clearly demonstrate the validity of both approaches for leakage-free sampling of amino acids in yeast.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Molecular dynamics simulation of subnanometric tool-workpiece contact on a force sensor-integrated fast tool servo for ultra-precision microcutting

    NASA Astrophysics Data System (ADS)

    Cai, Yindi; Chen, Yuan-Liu; Shimizu, Yuki; Ito, So; Gao, Wei; Zhang, Liangchi

    2016-04-01

    This paper investigates the contact characteristics between a copper workpiece and a diamond tool in a force sensor-integrated fast tool servo (FS-FTS) for single point diamond microcutting and in-process measurement of ultra-precision surface forms of the workpiece. Molecular dynamics (MD) simulations are carried out to identify the subnanometric elastic-plastic transition contact depth, at which the plastic deformation in the workpiece is initiated. This critical depth can be used to optimize the FS-FTS as well as the cutting/measurement process. It is clarified that the vibrations of the copper atoms in the MD model have a great influence on the subnanometric MD simulation results. A multi-relaxation time method is then proposed to reduce the influence of the atom vibrations based on the fact that the dominant vibration component has a certain period determined by the size of the MD model. It is also identified that for a subnanometric contact depth, the position of the tool tip for the contact force to be zero during the retracting operation of the tool does not correspond to the final depth of the permanent contact impression on the workpiece surface. The accuracy for identification of the transition contact depth is then improved by observing the residual defects on the workpiece surface after the tool retracting.

  14. 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.

  15. 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. PMID:26017815

  16. Intracellular targeting with engineered proteins.

    PubMed

    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.

  17. 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

  18. 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

  19. Intracellular trafficking of nucleic acids.

    PubMed

    Zhou, Rui; Geiger, R Christopher; Dean, David A

    2004-11-01

    Until recently, the attention of most researchers has focused on the first and last steps of gene transfer, namely delivery to the cell and transcription, in order to optimise transfection and gene therapy. However, over the past few years, researchers have realised that the intracellular trafficking of plasmids is more than just a "black box" and is actually one of the major barriers to effective gene delivery. After entering the cytoplasm, following direct delivery or endocytosis, plasmids or other vectors must travel relatively long distances through the mesh of cytoskeletal networks before reaching the nuclear envelope. Once at the nuclear envelope, the DNA must either wait until cell division, or be specifically transported through the nuclear pore complex, in order to reach the nucleoplasm where it can be transcribed. This review focuses on recent developments in the understanding of these intracellular trafficking events as they relate to gene delivery. Hopefully, by continuing to unravel the mechanisms by which plasmids and other gene delivery vectors move throughout the cell, and by understanding the cell biology of gene transfer, superior methods of transfection and gene therapy can be developed.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Intracellular Adenosine Triphosphate Delivery Enhanced Skin Wound Healing in Rabbits

    PubMed Central

    Wang, Jianpu; Zhang, Qunwei; Wan, Rong; Mo, Yiqun; Li, Ming; Tseng, Michael T.; Chien, Sufan

    2016-01-01

    Small unilamellar lipid vesicles were used to encapsulate adenosine triphosphate (ATP-vesicles) for intracellular energy delivery. This technique was tested in full-thickness skin wounds in 16 adult rabbits. One ear was rendered ischemic by using a minimally invasive surgery. The other ear served as a normal control. Four circular full-thickness wounds were created on the ventral side of each ear. ATP-vesicles or saline was used and the wounds were covered with Tegaderm (3M, St. Paul, MN). Dressing was changed and digital photos were taken daily until all the wounds were healed. The mean healing times of ATP-vesicles–treated wounds were significantly shorter than that of saline-treated wounds on ischemic and nonischemic ears. Histologic study indicated better-developed granular tissue and reepithelial-ization in the ATP-vesicles–treated wounds. The wounds treated by ATP-vesicles exhibited extremely fast granular tissue growth. More CD31 positive cells were seen in the ATP-vesicles–treated wounds. This preliminary study shows that direct intracellular delivery of ATP can accelerate the healing process of skin wounds on ischemic and nonischemic rabbit ears. The extremely fast granular tissue growth was something never seen or reported in the past. PMID:19158531

  8. 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

  9. Intracellular Shuttle: The Lactate Aerobic Metabolism

    PubMed Central

    Cruz, Rogério Santos de Oliveira; de Aguiar, Rafael Alves; Turnes, Tiago; Penteado Dos Santos, Rafael; Fernandes Mendes de Oliveira, Mariana; Caputo, Fabrizio

    2012-01-01

    Lactate is a highly dynamic metabolite that can be used as a fuel by several cells of the human body, particularly during physical exercise. Traditionally, it has been believed that the first step of lactate oxidation occurs in cytosol; however, this idea was recently challenged. A new hypothesis has been presented based on the fact that lactate-to-pyruvate conversion cannot occur in cytosol, because the LDH enzyme characteristics and cytosolic environment do not allow the reaction in this way. Instead, the Intracellular Lactate Shuttle hypothesis states that lactate first enters in mitochondria and only then is metabolized. In several tissues of the human body this idea is well accepted but is quite resistant in skeletal muscle. In this paper, we will present not only the studies which are protagonists in this discussion, but the potential mechanism by which this oxidation occurs and also a link between lactate and mitochondrial proliferation. This new perspective brings some implications and comes to change our understanding of the interaction between the energy systems, because the product of one serves as a substrate for the other. PMID:22593684

  10. 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. PMID:26431435

  11. Intracellular Ca 2+ nonlinear wave behaviours in a three dimensional ventricular cell model

    NASA Astrophysics Data System (ADS)

    Li, Pan; Holden, Arun V.

    2009-06-01

    Intracellular Ca 2+ activity regulates a wide range of cellular biochemical processes; in muscle cells, it links membrane excitation to contraction. Ca 2+ dynamics includes both synchronous oscillations, and nonlinear wave phenomena, both arising from the superposition of spatially localised stochastic events, such as Ca 2+ sparks. We incorporated individualised cell geometry reconstructed from confocal microscopy with realistic spatial distribution of RyR clusters into the three dimensional ventricular cell model, and reproduced complex spatio-temporal intracellular wave patterns from Ca 2+ sparks. We also introduced a detailed nuclear Ca 2+ handing model to simulate prolonged nuclear Ca 2+ transient, and study the effects of cytosolic-nuclear coupling on intracellular Ca 2+ dynamics. The model provides a computational platform to study intracellular Ca 2+ with the ability to interact with experimental measurements of subcellular structures, and can be modified for other cell types.

  12. 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

  13. 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.

  14. 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

  15. Single-cell intracellular nano-pH probes†

    PubMed Central

    Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

    2016-01-01

    Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular pH of individual cells within a cell population is challenging with existing technologies, and there is a need to engineer new methodologies. In this paper, we discuss the use of nanopipette technology to overcome the limitations of intracellular pH measurements at the single-cell level. We have developed a nano-pH probe through physisorption of chitosan onto hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of 0.09 units. We have performed single-cell intracellular pH measurements using non-cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231 and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time continuous single-cell pH measurement capability of the sensor, showing the cellular pH response to pharmaceutical manipulations. These findings suggest that the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at the single-cell level with high temporal and spatial resolution. PMID:27708772

  16. Single-cell intracellular nano-pH probes†

    PubMed Central

    Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

    2016-01-01

    Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular pH of individual cells within a cell population is challenging with existing technologies, and there is a need to engineer new methodologies. In this paper, we discuss the use of nanopipette technology to overcome the limitations of intracellular pH measurements at the single-cell level. We have developed a nano-pH probe through physisorption of chitosan onto hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of 0.09 units. We have performed single-cell intracellular pH measurements using non-cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231 and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time continuous single-cell pH measurement capability of the sensor, showing the cellular pH response to pharmaceutical manipulations. These findings suggest that the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at the single-cell level with high temporal and spatial resolution.

  17. 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

  18. Hydrophilic fluorescent nanogel thermometer for intracellular thermometry.

    PubMed

    Gota, Chie; Okabe, Kohki; Funatsu, Takashi; Harada, Yoshie; Uchiyama, Seiichi

    2009-03-01

    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.

  19. Intracellular alpha-keto acid quantification by fluorescence-HPLC.

    PubMed

    Fuchs, M; Engel, J; Campos, M; Matejec, R; Henrich, M; Harbach, H; Wolff, M; Weismüller, K; Menges, T; Heidt, M C; Welters, I D; Krüll, M; Hempelmann, G; Mühling, J

    2009-01-01

    Procedures for the analysis of free alpha-keto acids in human fluids (i.e. plasma, cerebrospinal fluid, urine, etc.) as well as for studying the dynamic free alpha-keto acid pools in differentiated tissues and organ cells have been the subject of growing clinical interest in the study of metabolic regulatory and pathophysiological phenomena. Due to the high instability and polarity of the alpha-keto acids being examined, the development of a quantitative and reproducible analysis of metabolically relevant intracellular alpha-keto acids still presents a substantial methodological challenge. The aim of small sample size, rapid, non-damaging and "metabolism-neutral" cell isolation, careful sample preparation and stability, as well as reproducible analytics technology is not often achieved. Only few of the methods described can satisfy the rigorous demands for an ultra-sensitive, comprehensive and rapid intracellular alpha-keto acid analysis.

  20. Complex patterns of mitochondrial dynamics in human pancreatic cells revealed by fluorescent confocal imaging.

    PubMed

    Kuznetsov, Andrey V; Hermann, Martin; Troppmair, Jakob; Margreiter, Raimund; Hengster, Paul

    2010-01-01

    Mitochondrial morphology and intracellular organization are tightly controlled by the processes of mitochondrial fission-fusion. Moreover, mitochondrial movement and redistribution provide a local ATP supply at cellular sites of particular demands. Here we analysed mitochondrial dynamics in isolated primary human pancreatic cells. Using real time confocal microscopy and mitochondria-specific fluorescent probes tetramethylrhodamine methyl ester and MitoTracker Green we documented complex and novel patterns of spatial and temporal organization of mitochondria, mitochondrial morphology and motility. The most commonly observed types of mitochondrial dynamics were (i) fast fission and fusion; (ii) small oscillating movements of the mitochondrial network; (iii) larger movements, including filament extension, retraction, fast (0.1-0.3 mum/sec.) and frequent oscillating (back and forth) branching in the mitochondrial network; (iv) as well as combinations of these actions and (v) long-distance intracellular translocation of single spherical mitochondria or separated mitochondrial filaments with velocity up to 0.5 mum/sec. Moreover, we show here for the first time, a formation of unusual mitochondrial shapes like rings, loops, and astonishingly even knots created from one or more mitochondrial filaments. These data demonstrate the presence of extensive heterogeneity in mitochondrial morphology and dynamics in living cells under primary culture conditions. In summary, this study reports new patterns of morphological changes and dynamic motion of mitochondria in human pancreatic cells, suggesting an important role of integrations of mitochondria with other intracellular structures and systems. PMID:19382913

  1. Intracellular calcium puffs in osteoclasts.

    PubMed

    Radding, W; Jordan, S E; Hester, R B; Blair, H C

    1999-12-15

    We studied intracellular calcium ([Ca(2+)](i)) in acid-secreting bone-attached osteoclasts, which produce a high-calcium acidic extracellular compartment. Acid secretion and [Ca(2+)](i) were followed using H(+)-restricted dyes and fura-2 or fluo-3. Whole cell calcium of acid-secreting osteoclasts was approximately 100 nM, similar to cells on inert substrate that do not secrete acid. However, measurements in restricted areas of the cell showed [Ca(2+)](i) transients to 500-1000 nM consistent with calcium puffs, transient (millisecond) localized calcium elevations reported in other cells. Spot measurements at 50-ms intervals indicated that puffs were typically less than 400 ms. Transients did not propagate in waves across the cell in scanning confocal measurements. Calcium puffs occurred mainly over regions of acid secretion as determined using lysotracker red DND99 and occurred at irregular periods averaging 5-15 s in acid secreting cells, but were rare in lysotracker-negative nonsecretory cells. The calmodulin antagonist trifluoperazine, cell-surface calcium transport inhibitors lanthanum or barium, and the endoplasmic reticulum ATPase inhibitor thapsigargin had variable acute effects on the mean [Ca(2+)](i) and puff frequency. However, none of these agents prevented calcium puff activity, suggesting that the mechanism producing the puffs is independent of these processes. We conclude that [Ca(2+)](i) transients in osteoclasts are increased in acid-secreting osteoclasts, and that the puffs occur mainly near the acid-transporting membrane. Cell membrane acid transport requires calcium, suggesting that calcium puffs function to maintain acid secretion. However, membrane H(+)-ATPase activity was insensitive to calcium in the 100 nM-1 microM range. Thus, any effects of calcium puffs on osteoclastic acid transport must be indirect.

  2. Intracellular periodontal pathogen exploits recycling pathway to exit from infected cells.

    PubMed

    Takeuchi, Hiroki; Takada, Akihiko; Kuboniwa, Masae; Amano, Atsuo

    2016-07-01

    Although human gingival epithelium prevents intrusions by periodontal bacteria, Porphyromonas gingivalis, the most well-known periodontal pathogen, is able to invade gingival epithelial cells and pass through the epithelial barrier into deeper tissues. We previously reported that intracellular P. gingivalis exits from gingival epithelial cells via a recycling pathway. However, the underlying molecular process remains unknown. In the present study, we found that the pathogen localized in early endosomes recruits VAMP2 and Rab4A. VAMP2 was found to be specifically localized in early endosomes, although its localization remained unclear in mammalian cells. A single transmembrane domain of VAMP2 was found to be necessary and sufficient for localizing in early endosomes containing P. gingivalis in gingival epithelial cells. VAMP2 forms a complex with EXOC2/Sec5 and EXOC3/Sec6, whereas Rab4A mediates dissociation of the EXOC complex followed by recruitment of RUFY1/Rabip4, Rab4A effector, and Rab14. Depletion of VAMP2 or Rab4A resulted in accumulation of bacteria in early endosomes and disturbed bacterial exit from infected cells. It is suggested that these novel dynamics allow P. gingivalis to exploit fast recycling pathways promoting further bacterial penetration of gingival tissues.

  3. Characterization of Zebrafish Green Cone Photoresponse Recorded with Pressure-Polished Patch Pipettes, Yielding Efficient Intracellular Dialysis.

    PubMed

    Aquila, Marco; Benedusi, Mascia; Fasoli, Anna; Rispoli, Giorgio

    2015-01-01

    The phototransduction enzymatic cascade in cones is less understood than in rods, and the zebrafish is an ideal model with which to investigate vertebrate and human vision. Therefore, here, for the first time, the zebrafish green cone photoresponse is characterized also to obtain a firm basis for evaluating how it is modulated by exogenous molecules. To this aim, a powerful method was developed to obtain long-lasting recordings with low access resistance, employing pressure-polished patch pipettes. This method also enabled fast, efficient delivery of molecules via a perfusion system coupled with pulled quartz or plastic perfusion tubes, inserted very close to the enlarged pipette tip. Sub-saturating flashes elicited responses in different cells with similar rising phase kinetics but with very different recovery kinetics, suggesting the existence of physiologically distinct cones having different Ca2+ dynamics. Theoretical considerations demonstrate that the different recovery kinetics can be modelled by simulating changes in the Ca2+-buffering capacity of the outer segment. Importantly, the Ca2+-buffer action preserves the fast response rising phase, when the Ca2+-dependent negative feedback is activated by the light-induced decline in intracellular Ca2+. PMID:26513584

  4. Characterization of Zebrafish Green Cone Photoresponse Recorded with Pressure-Polished Patch Pipettes, Yielding Efficient Intracellular Dialysis

    PubMed Central

    Aquila, Marco; Benedusi, Mascia; Fasoli, Anna; Rispoli, Giorgio

    2015-01-01

    The phototransduction enzymatic cascade in cones is less understood than in rods, and the zebrafish is an ideal model with which to investigate vertebrate and human vision. Therefore, here, for the first time, the zebrafish green cone photoresponse is characterized also to obtain a firm basis for evaluating how it is modulated by exogenous molecules. To this aim, a powerful method was developed to obtain long-lasting recordings with low access resistance, employing pressure-polished patch pipettes. This method also enabled fast, efficient delivery of molecules via a perfusion system coupled with pulled quartz or plastic perfusion tubes, inserted very close to the enlarged pipette tip. Sub-saturating flashes elicited responses in different cells with similar rising phase kinetics but with very different recovery kinetics, suggesting the existence of physiologically distinct cones having different Ca2+ dynamics. Theoretical considerations demonstrate that the different recovery kinetics can be modelled by simulating changes in the Ca2+-buffering capacity of the outer segment. Importantly, the Ca2+-buffer action preserves the fast response rising phase, when the Ca2+-dependent negative feedback is activated by the light-induced decline in intracellular Ca2+. PMID:26513584

  5. Stochastic resonance in an intracellular genetic perceptron

    NASA Astrophysics Data System (ADS)

    Bates, Russell; Blyuss, Oleg; Zaikin, Alexey

    2014-03-01

    Intracellular genetic networks are more intelligent than was first assumed due to their ability to learn. One of the manifestations of this intelligence is the ability to learn associations of two stimuli within gene-regulating circuitry: Hebbian-type learning within the cellular life. However, gene expression is an intrinsically noisy process; hence, we investigate the effect of intrinsic and extrinsic noise on this kind of intracellular intelligence. We report a stochastic resonance in an intracellular associative genetic perceptron, a noise-induced phenomenon, which manifests itself in noise-induced increase of response in efficiency after the learning event under the conditions of optimal stochasticity.

  6. Visualization of Intracellular Tyrosinase Activity in vitro

    PubMed Central

    Setty, Subba Rao Gangi

    2016-01-01

    Melanocytes produce the melanin pigments in melanosomes and these organelles protect the skin against harmful ultraviolet rays. Tyrosinase is the key cuproenzyme which initiates the pigment synthesis using its substrate amino acid tyrosine or L-DOPA (L-3, 4-dihydroxyphenylalanine). Moreover, the activity of tyrosinase directly correlates to the cellular pigmentation. Defects in tyrosinase transport to melanosomes or mutations in the enzyme or reduced intracellular copper levels results in loss of tyrosinase activity in melanosomes, commonly observed in albinism. Here, we described a method to detect the intracellular activity of tyrosinase in mouse melanocytes. This protocol will visualize the active tyrosinase present in the intracellular vesicles or organelles including melanosomes. PMID:27231711

  7. Spatial aspects of intracellular information processing.

    PubMed

    Kinkhabwala, Ali; Bastiaens, Philippe I H

    2010-02-01

    The computational properties of intracellular biochemical networks, for which the cell is assumed to be a 'well-mixed' reactor, have already been widely characterized. What has so far not received systematic treatment is the important role of space in many intracellular computations. Spatial network computations can be divided into two broad categories: those required for essential spatial processes (e.g. polarization, chemotaxis, division, and development) and those for which space is simply used as an extra dimension to expand the computational power of the network. Several pertinent recent examples of each category are discussed that illustrate the often conceptually subtle role of space in the processing of intracellular information. PMID:20096560

  8. 1H-13C/1H-15N Heteronuclear Dipolar Recoupling by R-Symmetry Sequences Under Fast Magic Angle Spinning for Dynamics Analysis of Biological and Organic Solids

    PubMed Central

    Hou, Guangjin; Byeon, In-Ja L.; Ahn, Jinwoo; Gronenborn, Angela M.; Polenova, Tatyana

    2011-01-01

    Fast magic angle spinning (MAS) NMR spectroscopy is becoming increasingly important in structural and dynamics studies of biological systems and inorganic materials. Superior spectral resolution due to the efficient averaging of the dipolar couplings can be attained at MAS frequencies of 40 kHz and higher with appropriate decoupling techniques, while proton detection gives rise to significant sensitivity gains, therefore making fast MAS conditions advantageous across the board compared with the conventional slow- and moderate-MAS approaches. At the same time, many of the dipolar recoupling approaches that currently constitute the basis for structural and dynamics studies of solid materials and that are designed for MAS frequencies of 20 kHz and below, fail above 30 kHz. In this report, we present an approach for 1H-13C/1H-15N heteronuclear dipolar recoupling under fast MAS conditions using R-type symmetry sequences, which is suitable even for fully protonated systems. A series of rotor-synchronized R-type symmetry pulse schemes are explored for the determination of structure and dynamics in biological and organic systems. The investigations of the performance of the various RNnv-symmetry sequences at the MAS frequency of 40 kHz experimentally and by numerical simulations on [U-13C,15N]-alanine and [U-13C,15N]-N-acetyl-valine, revealed excellent performance for sequences with high symmetry number ratio (N/2n > 2.5). Further applications of this approach are presented for two proteins, sparsely 13C/uniformly 15N enriched CAP-Gly domain of dynactin and U-13C,15N-Tyr enriched C-terminal domain of HIV-1 CA protein. 2D and 3D R1632-based DIPSHIFT experiments carried out at the MAS frequency of 40 kHz, yielded site-specific 1H-13C/1H-15N heteronuclear dipolar coupling constants for CAP-Gly and CTD CA, reporting on the dynamic behavior of these proteins on time scales of nano- to microseconds. The R-symmetry based dipolar recoupling under fast MAS is expected to find

  9. 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.

  10. Potent Antibacterial Nanoparticles against Biofilm and Intracellular Bacteria

    PubMed Central

    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. PMID:26728712

  11. 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

  12. 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.

  13. ApoHRP-based assay to measure intracellular regulatory heme.

    PubMed

    Atamna, Hani; Brahmbhatt, Marmik; Atamna, Wafa; Shanower, Gregory A; Dhahbi, Joseph M

    2015-02-01

    The majority of the heme-binding proteins possess a "heme-pocket" that stably binds to heme. Usually known as housekeeping heme-proteins, they participate in a variety of metabolic reactions (e.g., catalase). Heme also binds with lower affinity to the "Heme-Regulatory Motifs" (HRM) in specific regulatory proteins. This type of heme binding is known as exchangeable or regulatory heme (RH). Heme binding to HRM proteins regulates their function (e.g., Bach1). Although there are well-established methods for assaying total cellular heme (e.g., heme-proteins plus RH), currently there is no method available for measuring RH independent of the total heme (TH). The current study describes and validates a new method to measure intracellular RH. This method is based on the reconstitution of apo-horseradish peroxidase (apoHRP) with heme to form holoHRP. The resulting holoHRP activity is then measured with a colorimetric substrate. The results show that apoHRP specifically binds RH but not with heme from housekeeping heme-proteins. The RH assay detects intracellular RH. Furthermore, using conditions that create positive (hemin) or negative (N-methyl protoporphyrin IX) controls for heme in normal human fibroblasts (IMR90), the RH assay shows that RH is dynamic and independent of TH. We also demonstrated that short-term exposure to subcytotoxic concentrations of lead (Pb), mercury (Hg), or amyloid-β (Aβ) significantly alters intracellular RH with little effect on TH. In conclusion the RH assay is an effective assay to investigate intracellular RH concentration and demonstrates that RH represents ∼6% of total heme in IMR90 cells. PMID:25525887

  14. ApoHRP-based Assay to Measure Intracellular Regulatory Heme

    PubMed Central

    Atamna, Hani; Brahmbhatt, Marmik; Atamna, Wafa; Shanower, Gregory A.; Dhahbi, Joseph M.

    2015-01-01

    The majority of the heme-binding proteins possess a “heme-pocket” that stably binds with heme. Usually known as housekeeping heme-proteins, they participate in a variety of metabolic reactions (e.g., catalase). Heme also binds with lower affinity to the “Heme-Regulatory Motifs” (HRM) in specific regulatory proteins. This type of heme binding is known as exchangeable or regulatory heme (RH). Heme binding to HRM proteins regulates their function (e.g., Bach1). Although there are well-established methods for assaying total cellular heme (e.g., heme-proteins plus RH), currently there is no method available for measuring RH independently from the total heme (TH). The current study describes and validates a new method to measure intracellular RH. The method is based on the reconstitution of apo-horseradish peroxidase (apoHRP) with heme to form holoHRP. The resulting holoHRP activity is then measured with a colorimetric substrate. The results show that apoHRP specifically binds RH but not with heme from housekeeping heme-proteins. The RH assay detects intracellular RH. Furthermore, using conditions that create positive (hemin) or negative (N-methyl protoporphyrin IX) controls for heme in normal human fibroblasts (IMR90), the RH assay shows that RH is dynamic and independent from TH. We also demonstrated that short-term exposure to subcytotoxic concentrations of lead (Pb), mercury (Hg), or amyloid-β(Aβ) significantly alters intracellular RH with little effect on TH. In conclusion the RH assay is an effective assay to investigate intracellular RH concentration and demonstrates that RH represents ~6% of total heme in IMR90 cells. PMID:25525887

  15. 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

  16. Nanoscale Label-free Bioprobes to Detect Intracellular Proteins in Single Living Cells

    PubMed Central

    Hong, Wooyoung; Liang, Feng; Schaak, Diane; Loncar, Marko; Quan, Qimin

    2014-01-01

    Fluorescent labeling techniques have been widely used in live cell studies; however, the labeling processes can be laborious and challenging for use in non-transfectable cells, and labels can interfere with protein functions. While label-free biosensors have been realized by nanofabrication, a method to track intracellular protein dynamics in real-time, in situ and in living cells has not been found. Here we present the first demonstration of label-free detection of intracellular p53 protein dynamics through a nanoscale surface plasmon-polariton fiber-tip-probe (FTP). PMID:25154394

  17. Nanoscale Label-free Bioprobes to Detect Intracellular Proteins in Single Living Cells

    NASA Astrophysics Data System (ADS)

    Hong, Wooyoung; Liang, Feng; Schaak, Diane; Loncar, Marko; Quan, Qimin

    2014-08-01

    Fluorescent labeling techniques have been widely used in live cell studies; however, the labeling processes can be laborious and challenging for use in non-transfectable cells, and labels can interfere with protein functions. While label-free biosensors have been realized by nanofabrication, a method to track intracellular protein dynamics in real-time, in situ and in living cells has not been found. Here we present the first demonstration of label-free detection of intracellular p53 protein dynamics through a nanoscale surface plasmon-polariton fiber-tip-probe (FTP).

  18. Intracellular Microrheology of Motile Amoeba proteus

    NASA Astrophysics Data System (ADS)

    Rogers, S.; Waigh, T.; Lu, J.

    2008-04-01

    The motility of motile Amoeba proteus was examined using the technique of passive particle tracking microrheology, with the aid of newly-developed particle tracking software, a fast digital camera and an optical microscope. We tracked large numbers of endogeneous particles in the amoebae, which displayed subdiffusive motion at short time scales, corresponding to thermal motion in a viscoelastic medium, and superdiffusive motion at long time scales due to the convection of the cytoplasm. Subdiffusive motion was characterised by a rheological scaling exponent of 3/4 in the cortex, indicative of the semiflexible dynamics of the actin fibres. We observed shear-thinning in the flowing endoplasm, where exponents increased with increasing flow rate; i.e. the endoplasm became more fluid-like. The rheology of the cortex is found to be isotropic, reflecting an isotropic actin gel. A clear difference was seen between cortical and endoplasmic layers in terms of both viscoelasticity and flow velocity, where the profile of the latter is close to a Poiseuille flow for a Newtonian fluid.

  19. Synthetic nanocarriers for intracellular protein delivery.

    PubMed

    Du, Juanjuan; Jin, Jing; Yan, Ming; Lu, Yunfeng

    2012-01-01

    Introducing exogenous proteins intracellularly presents tremendous chances in scientific research and clinical applications. The effectiveness of this method, however, has been limited by lack of efficient ways to achieve intracellular protein delivery and poor stability of the delivered proteins. Over the years, a variety of nanomaterials have been explored as intracellular protein delivery vectors, including liposomes, polymers, gold nanoparticles, mesoporous silica particles, and carbon nanotubes. Nanomaterials stand out in various protein delivery systems due to various advantages, such as efficient intracellular delivery, long circulation time, and passive tumor targeting. Additionally, chemistry behind these nanomaterials provides readily engineered materials, enabling versatile designs of delivery agents. Intracellular delivery mediated by such nanocarriers achieved varying degrees of success. Different problems associated with these nanocarriers, however, still hamper their real-world applications. Developing new delivery methods or vectors remains essential but challenging. This review surveys the current developments in protein delivery based on synthetic nanocarriers, including liposomes, polymers and inorganic nanocarriers; Prospects for future development of protein delivery nanocarriers are also provided.

  20. Localization of Mycobacterium avium-intracellulare within a skin lesion of bacillary angiomatosis in a patient with AIDS.

    PubMed

    Sagerman, P M; Relman, D A; Niroomand, F; Niedt, G W

    1992-09-01

    We report a 39-year-old man who had AIDS and who presented with an unusual cutaneous vascular lesion, which was clinically thought to be Kaposi's sarcoma. Histologically, the lesion was characterized by capillary proliferation and a mixed inflammatory infiltrate that included numerous histiocytes. The lesion was found to contain slender intracellular acid-fast bacilli, as well as plump extracellular Warthin-Starry-positive bacilli. The acid-fast bacilli were confirmed to be Mycobacterium avium-intracellulare by subsequent positive blood cultures for this organism. To further investigate the lesion, polymerase chain reaction DNA amplification and sequencing was performed, and the lesion was found to contain DNA sequences identical to those previously established for the agent of bacillary angiomatosis. The lesion is thought to represent a lesion of bacillary angiomatosis with secondary involvement by M. avium-intracellulare.

  1. 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.

  2. 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.

  3. 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.

  4. Macrophage defense mechanisms against intracellular bacteria

    PubMed Central

    Weiss, Günter; Schaible, Ulrich E

    2015-01-01

    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. PMID:25703560

  5. Endosomal escape: a bottleneck in intracellular delivery.

    PubMed

    Shete, Harshad K; Prabhu, Rashmi H; Patravale, Vandana B

    2014-01-01

    With advances in therapeutic science, apart from drugs, newer bioactive moieties like oligonucleotides, proteins, peptides, enzymes and antibodies are constantly being introduced for the betterment of therapeutic efficacy. These moieties have intracellular components of the cells like cytoplasm and nucleus as one of their pharmacological sites for exhibiting therapeutic activity. Despite their promising efficacy, their intracellular bioavailability has been critically hampered leading to failure in the treatment of numerous diseases and disorders. The endosomal uptake pathway is known to be a rate-limiting barrier for such systems. Bioactive molecules get trapped in the endosomal vesicles and degraded in the lysosomal compartment, necessitating the need for effective strategies that facilitate the endosomal escape and enhance the cytosolic bioavailability of bioactives. Microbes like viruses and bacteria have developed their innate mechanistic tactics to translocate their genome and toxins by efficiently penetrating the host cell membrane. Understanding this mechanism and exploring it further for intracellular delivery has opened new avenues to surmount the endosomal barrier. These strategies include membrane fusion, pore formation and proton sponge effects. On the other hand, progress in designing a novel smart polymeric carrier system that triggers endosomal escape by undergoing modulations in the intracellular milieu has further led to an improvement in intracellular delivery. These comprise pH, enzyme and temperature-induced modulators, synthetic cationic lipids and photo-induced physical disruption. Each of the aforementioned strategies has its own unique mechanism to escape the endosome. This review recapitulates the numerous strategies designed to surmount the bottleneck of endosomal escape and thereby achieve successful intracellular uptake of bioactives. PMID:24730275

  6. 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. PMID:25703560

  7. Multiplexed imaging of intracellular protein networks.

    PubMed

    Grecco, Hernán E; Imtiaz, Sarah; Zamir, Eli

    2016-08-01

    Cellular functions emerge from the collective action of a large number of different proteins. Understanding how these protein networks operate requires monitoring their components in intact cells. Due to intercellular and intracellular molecular variability, it is important to monitor simultaneously multiple components at high spatiotemporal resolution. However, inherent trade-offs narrow the boundaries of achievable multiplexed imaging. Pushing these boundaries is essential for a better understanding of cellular processes. Here the motivations, challenges and approaches for multiplexed imaging of intracellular protein networks are discussed. © 2016 International Society for Advancement of Cytometry. PMID:27183498

  8. Peroxisome is a reservoir of intracellular calcium.

    PubMed

    Raychaudhury, Bikramjit; Gupta, Shreedhara; Banerjee, Shouvik; Datta, Salil C

    2006-07-01

    We have examined fura 2-loaded purified peroxisomes under confocal microscope to prove that this mammalian organelle is a store of intracellular calcium pool. Presence of calcium channel and vanadate sensitive Ca(2+)-ATPase in the purified peroxisomal membrane has been demonstrated. We have further observed that machineries to maintain calcium pool in this mammalian organelle are impaired during infection caused by Leishmania donovani. Results reveal that peroxisomes have a merit to play a significant role in the metabolism of intracellular calcium. PMID:16713100

  9. 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.

  10. FAST: FAST Analysis of Sequences Toolbox

    PubMed Central

    Lawrence, Travis J.; Kauffman, Kyle T.; Amrine, Katherine C. H.; Carper, Dana L.; Lee, Raymond S.; Becich, Peter J.; Canales, Claudia J.; Ardell, David H.

    2015-01-01

    FAST (FAST Analysis of Sequences Toolbox) provides simple, powerful open source command-line tools to filter, transform, annotate and analyze biological sequence data. Modeled after the GNU (GNU's Not Unix) Textutils such as grep, cut, and tr, FAST tools such as fasgrep, fascut, and fastr make it easy to rapidly prototype expressive bioinformatic workflows in a compact and generic command vocabulary. Compact combinatorial encoding of data workflows with FAST commands can simplify the documentation and reproducibility of bioinformatic protocols, supporting better transparency in biological data science. Interface self-consistency and conformity with conventions of GNU, Matlab, Perl, BioPerl, R, and GenBank help make FAST easy and rewarding to learn. FAST automates numerical, taxonomic, and text-based sorting, selection and transformation of sequence records and alignment sites based on content, index ranges, descriptive tags, annotated features, and in-line calculated analytics, including composition and codon usage. Automated content- and feature-based extraction of sites and support for molecular population genetic statistics make FAST useful for molecular evolutionary analysis. FAST is portable, easy to install and secure thanks to the relative maturity of its Perl and BioPerl foundations, with stable releases posted to CPAN. Development as well as a publicly accessible Cookbook and Wiki are available on the FAST GitHub repository at https://github.com/tlawrence3/FAST. The default data exchange format in FAST is Multi-FastA (specifically, a restriction of BioPerl FastA format). Sanger and Illumina 1.8+ FastQ formatted files are also supported. FAST makes it easier for non-programmer biologists to interactively investigate and control biological data at the speed of thought. PMID:26042145

  11. FAST: FAST Analysis of Sequences Toolbox.

    PubMed

    Lawrence, Travis J; Kauffman, Kyle T; Amrine, Katherine C H; Carper, Dana L; Lee, Raymond S; Becich, Peter J; Canales, Claudia J; Ardell, David H

    2015-01-01

    FAST (FAST Analysis of Sequences Toolbox) provides simple, powerful open source command-line tools to filter, transform, annotate and analyze biological sequence data. Modeled after the GNU (GNU's Not Unix) Textutils such as grep, cut, and tr, FAST tools such as fasgrep, fascut, and fastr make it easy to rapidly prototype expressive bioinformatic workflows in a compact and generic command vocabulary. Compact combinatorial encoding of data workflows with FAST commands can simplify the documentation and reproducibility of bioinformatic protocols, supporting better transparency in biological data science. Interface self-consistency and conformity with conventions of GNU, Matlab, Perl, BioPerl, R, and GenBank help make FAST easy and rewarding to learn. FAST automates numerical, taxonomic, and text-based sorting, selection and transformation of sequence records and alignment sites based on content, index ranges, descriptive tags, annotated features, and in-line calculated analytics, including composition and codon usage. Automated content- and feature-based extraction of sites and support for molecular population genetic statistics make FAST useful for molecular evolutionary analysis. FAST is portable, easy to install and secure thanks to the relative maturity of its Perl and BioPerl foundations, with stable releases posted to CPAN. Development as well as a publicly accessible Cookbook and Wiki are available on the FAST GitHub repository at https://github.com/tlawrence3/FAST. The default data exchange format in FAST is Multi-FastA (specifically, a restriction of BioPerl FastA format). Sanger and Illumina 1.8+ FastQ formatted files are also supported. FAST makes it easier for non-programmer biologists to interactively investigate and control biological data at the speed of thought.

  12. How to Read Faster and Better. The Evelyn Wood Reading Dynamics Program. How to Get Everything You Want from Anything You Read as Fast as You Can Think.

    ERIC Educational Resources Information Center

    Agardy, Franklin J.

    Written so that the reader participates almost as if in a game, this book is aimed at achieving five goals: reading faster, understanding better, remembering longer, learning more easily, and thinking more clearly. Chapters discuss the following: (1) reading dynamics; (2) Evelyn Wood; (3) how to increase reading speed; (4) how to increase…

  13. 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

  14. Open LED Illuminator: A Simple and Inexpensive LED Illuminator for Fast Multicolor Particle Tracking in Neurons.

    PubMed

    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.

  15. [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.

  16. Intracellular transduction using cell-penetrating peptides.

    PubMed

    Sawant, Rupa; Torchilin, Vladimir

    2010-04-01

    Cell penetrating peptides (CPPs), TATp, in particular, has been used widely for intracellular delivery of various agents ranging from small molecules to proteins, peptides, range of pharmaceutical nanocarriers and imaging agents. This review highlights the mechanisms of CPP-mediated delivery and summarizes numerous examples illustrating the potential of CPPs in the fields of biology and medicine. PMID:20237640

  17. Histoplasma capsulatum surmounts obstacles to intracellular pathogenesis.

    PubMed

    Garfoot, Andrew L; Rappleye, Chad A

    2016-02-01

    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

  18. Digital Holography of Intracellular Dynamics to Probe Tissue Physiology

    PubMed Central

    Merrill, Daniel; An, Ran; Turek, John; Nolte, David D.

    2015-01-01

    Digital holography provides improved capabilities for imaging through dense tissue. Using a short-coherence source, the digital hologram recorded from backscattered light performs laser ranging that maintains fidelity of information acquired from depths much greater than possible by traditional imaging techniques. Biodynamic Imaging (BDI) is a developing technology for live-tissue imaging of up to a millimeter in depth that uses the hologram intensity fluctuations as label-free image contrast and can study tissue behavior in native microenvironments. In this paper BDI is used investigate the change in adhesion-dependent tissue response in 3D cultures. The results show that increasing density of cellular adhesions slows motion inside tissue and alters the response to cytoskeletal drugs. A clear signature of membrane fluctuations was observed in mid frequencies (0.1 – 1 Hz) that was enhanced by the application of cytochalasin-D that degrades the actin cortex inside the cell membrane. This enhancement feature is only observed in tissues that have formed adhesions, because cell pellets initially do not show this signature, but develop this signature only after incubation enables adhesions to form. PMID:25967027

  19. Digital holography of intracellular dynamics to probe tissue physiology.

    PubMed

    Merrill, Daniel; An, Ran; Turek, John; Nolte, David D

    2015-01-01

    Digital holography provides improved capabilities for imaging through dense tissue. Using a short-coherence source, the digital hologram recorded from backscattered light performs laser ranging that maintains fidelity of information acquired from depths much greater than possible by traditional imaging techniques. Biodynamic imaging (BDI) is a developing technology for live-tissue imaging of up to a millimeter in depth that uses the hologram intensity fluctuations as label-free image contrast and can study tissue behavior in native microenvironments. In this paper BDI is used to investigate the change in adhesion-dependent tissue response in 3D cultures. The results show that increasing density of cellular adhesions slows motion inside tissue and alters the response to cytoskeletal drugs. A clear signature of membrane fluctuations was observed in mid-frequencies (0.1-1 Hz) and was enhanced by the application of cytochalasin-D that degrades the actin cortex inside the cell membrane. This enhancement feature is only observed in tissues that have formed adhesions, because cell pellets initially do not show this signature, but develop this signature only after incubation enables adhesions to form.

  20. Intracellular Dynamics of the Ubiquitin-Proteasome-System.

    PubMed

    Chowdhury, Maisha; Enenkel, Cordula

    2015-01-01

    The ubiquitin-proteasome system is the major degradation pathway for short-lived proteins in eukaryotic cells. Targets of the ubiquitin-proteasome-system are proteins regulating a broad range of cellular processes including cell cycle progression, gene expression, the quality control of proteostasis and the response to geno- and proteotoxic stress. Prior to degradation, the proteasomal substrate is marked with a poly-ubiquitin chain. The key protease of the ubiquitin system is the proteasome. In dividing cells, proteasomes exist as holo-enzymes composed of regulatory and core particles. The regulatory complex confers ubiquitin-recognition and ATP dependence on proteasomal protein degradation. The catalytic sites are located in the proteasome core particle. Proteasome holo-enzymes are predominantly nuclear suggesting a major requirement for proteasomal proteolysis in the nucleus. In cell cycle arrested mammalian or quiescent yeast cells, proteasomes deplete from the nucleus and accumulate in granules at the nuclear envelope (NE) / endoplasmic reticulum (ER) membranes. In prolonged quiescence, proteasome granules drop off the NE / ER membranes and migrate as stable organelles throughout the cytoplasm, as thoroughly investigated in yeast. When quiescence yeast cells are allowed to resume growth, proteasome granules clear and proteasomes are rapidly imported into the nucleus. Here, we summarize our knowledge about the enigmatic structure of proteasome storage granules and the trafficking of proteasomes and their substrates between the cyto- and nucleoplasm. Most of our current knowledge is based on studies in yeast. Their translation to mammalian cells promises to provide keen insight into protein degradation in non-dividing cells which comprise the majority of our body's cells. PMID:26339477