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Sample records for dynamics underlying neurite

  1. Neurite-specific Ca2+ dynamics underlying sound processing in an auditory interneurone.

    PubMed

    Baden, T; Hedwig, B

    2007-01-01

    Concepts on neuronal signal processing and integration at a cellular and subcellular level are driven by recording techniques and model systems available. The cricket CNS with the omega-1-neurone (ON1) provides a model system for auditory pattern recognition and directional processing. Exploiting ON1's planar structure we simultaneously imaged free intracellular Ca(2+) at both input and output neurites and recorded the membrane potential in vivo during acoustic stimulation. In response to a single sound pulse the rate of Ca(2+) rise followed the onset spike rate of ON1, while the final Ca(2+) level depended on the mean spike rate. Ca(2+) rapidly increased in both dendritic and axonal arborizations and only gradually in the axon and the cell body. Ca(2+) levels were particularly high at the spike-generating zone. Through the activation of a Ca(2+)-sensitive K(+) current this may exhibit a specific control over the cell's electrical response properties. In all cellular compartments presentation of species-specific calling song caused distinct oscillations of the Ca(2+) level in the chirp rhythm, but not the faster syllable rhythm. The Ca(2+)-mediated hyperpolarization of ON1 suppressed background spike activity between chirps, acting as a noise filter. During directional auditory processing, the functional interaction of Ca(2+)-mediated inhibition and contralateral synaptic inhibition was demonstrated. Upon stimulation with different sound frequencies, the dendrites, but not the axonal arborizations, demonstrated a tonotopic response profile. This mirrored the dominance of the species-specific carrier frequency and resulted in spatial filtering of high frequency auditory inputs. PMID:17443773

  2. Neurite, a Finite Difference Large Scale Parallel Program for the Simulation of Electrical Signal Propagation in Neurites under Mechanical Loading

    PubMed Central

    García-Grajales, Julián A.; Rucabado, Gabriel; García-Dopico, Antonio; Peña, José-María; Jérusalem, Antoine

    2015-01-01

    With the growing body of research on traumatic brain injury and spinal cord injury, computational neuroscience has recently focused its modeling efforts on neuronal functional deficits following mechanical loading. However, in most of these efforts, cell damage is generally only characterized by purely mechanistic criteria, functions of quantities such as stress, strain or their corresponding rates. The modeling of functional deficits in neurites as a consequence of macroscopic mechanical insults has been rarely explored. In particular, a quantitative mechanically based model of electrophysiological impairment in neuronal cells, Neurite, has only very recently been proposed. In this paper, we present the implementation details of this model: a finite difference parallel program for simulating electrical signal propagation along neurites under mechanical loading. Following the application of a macroscopic strain at a given strain rate produced by a mechanical insult, Neurite is able to simulate the resulting neuronal electrical signal propagation, and thus the corresponding functional deficits. The simulation of the coupled mechanical and electrophysiological behaviors requires computational expensive calculations that increase in complexity as the network of the simulated cells grows. The solvers implemented in Neurite—explicit and implicit—were therefore parallelized using graphics processing units in order to reduce the burden of the simulation costs of large scale scenarios. Cable Theory and Hodgkin-Huxley models were implemented to account for the electrophysiological passive and active regions of a neurite, respectively, whereas a coupled mechanical model accounting for the neurite mechanical behavior within its surrounding medium was adopted as a link between electrophysiology and mechanics. This paper provides the details of the parallel implementation of Neurite, along with three different application examples: a long myelinated axon, a segmented

  3. Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling.

    PubMed

    Fusco, Ludovico; Lefort, Riwal; Smith, Kevin; Benmansour, Fethallah; Gonzalez, German; Barillari, Caterina; Rinn, Bernd; Fleuret, Francois; Fua, Pascal; Pertz, Olivier

    2016-01-01

    Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth. PMID:26728857

  4. Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling

    PubMed Central

    Fusco, Ludovico; Lefort, Riwal; Smith, Kevin; Benmansour, Fethallah; Gonzalez, German; Barillari, Caterina; Rinn, Bernd; Fleuret, Francois; Fua, Pascal

    2016-01-01

    Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth. PMID:26728857

  5. New potent accelerator of neurite outgrowth from Lawsonia inermis flower under non-fasting condition.

    PubMed

    Oda, Yoshimi; Nakashima, Souichi; Nakamura, Seikou; Yano, Mamiko; Akiyama, Masanori; Imai, Kayo; Kimura, Tomohito; Nakata, Akiko; Tani, Miyuki; Matsuda, Hisashi

    2016-07-01

    The methanolic extract of Lawsonia inermis L. (henna) showed accelerative effects on nerve growth factor-induced neurite outgrowth in PC12 cells under non-fasting conditions. To elucidate the active constituents responsible for the neuronal differentiation, we conducted a search of the constituents and examined their accelerative effects on neurite outgrowth in PC12 cells. We isolated a new acetophenone glycoside, inermioside A, which exerted a significant accelerative effect on neurite outgrowth. We also confirmed the activities of nine known compounds, including quercetin and lalioside. In addition, we found that quercetin, one of the active constituents, increased Vav3 mRNA expression. PMID:26936787

  6. Uridine from Pleurotus giganteus and Its Neurite Outgrowth Stimulatory Effects with Underlying Mechanism

    PubMed Central

    Phan, Chia-Wei; David, Pamela; Wong, Kah-Hui; Naidu, Murali; Sabaratnam, Vikineswary

    2015-01-01

    Neurodegenerative diseases are linked to neuronal cell death and impairment of neurite outgrowth. An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated. The chemical constituents of P. giganteus (linoleic acid, oleic acid, cinnamic acid, caffeic acid, p-coumaric acid, succinic acid, benzoic acid, and uridine) were tested for neurite outgrowth activity. Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1±0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells. Uridine which was present in P. giganteus (1.80±0.03 g/100g mushroom extract) increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Further, phosphorylation of the mammalian target of rapamycin (mTOR) was also increased. MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells. This study demonstrated that P. giganteus may enhance neurite outgrowth and one of the key bioactive molecules responsible for neurite outgrowth is uridine. PMID:26565787

  7. Uridine from Pleurotus giganteus and Its Neurite Outgrowth Stimulatory Effects with Underlying Mechanism.

    PubMed

    Phan, Chia-Wei; David, Pamela; Wong, Kah-Hui; Naidu, Murali; Sabaratnam, Vikineswary

    2015-01-01

    Neurodegenerative diseases are linked to neuronal cell death and impairment of neurite outgrowth. An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated. The chemical constituents of P. giganteus (linoleic acid, oleic acid, cinnamic acid, caffeic acid, p-coumaric acid, succinic acid, benzoic acid, and uridine) were tested for neurite outgrowth activity. Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1 ± 0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells. Uridine which was present in P. giganteus (1.80 ± 0.03 g/100g mushroom extract) increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Further, phosphorylation of the mammalian target of rapamycin (mTOR) was also increased. MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells. This study demonstrated that P. giganteus may enhance neurite outgrowth and one of the key bioactive molecules responsible for neurite outgrowth is uridine. PMID:26565787

  8. Dynamic peripheral traction forces balance stable neurite tension in regenerating Aplysia bag cell neurons

    PubMed Central

    Hyland, Callen; Mertz, Aaron F.; Forscher, Paul; Dufresne, Eric

    2014-01-01

    Growth cones of elongating neurites exert force against the external environment, but little is known about the role of force in outgrowth or its relationship to the mechanical organization of neurons. We used traction force microscopy to examine patterns of force in growth cones of regenerating Aplysia bag cell neurons. We find that traction is highest in the peripheral actin-rich domain and internal stress reaches a plateau near the transition between peripheral and central microtubule-rich domains. Integrating stress over the area of the growth cone reveals that total scalar force increases with area but net tension on the neurite does not. Tensions fall within a limited range while a substantial fraction of the total force can be balanced locally within the growth cone. Although traction continuously redistributes during extension and retraction of the peripheral domain, tension is stable over time, suggesting that tension is a tightly regulated property of the neurite independent of growth cone dynamics. We observe that redistribution of traction in the peripheral domain can reorient the end of the neurite shaft. This suggests a role for off-axis force in growth cone turning and neuronal guidance. PMID:24825441

  9. Dynamic peripheral traction forces balance stable neurite tension in regenerating Aplysia bag cell neurons.

    PubMed

    Hyland, Callen; Mertz, Aaron F; Forscher, Paul; Dufresne, Eric

    2014-01-01

    Growth cones of elongating neurites exert force against the external environment, but little is known about the role of force in outgrowth or its relationship to the mechanical organization of neurons. We used traction force microscopy to examine patterns of force in growth cones of regenerating Aplysia bag cell neurons. We find that traction is highest in the peripheral actin-rich domain and internal stress reaches a plateau near the transition between peripheral and central microtubule-rich domains. Integrating stress over the area of the growth cone reveals that total scalar force increases with area but net tension on the neurite does not. Tensions fall within a limited range while a substantial fraction of the total force can be balanced locally within the growth cone. Although traction continuously redistributes during extension and retraction of the peripheral domain, tension is stable over time, suggesting that tension is a tightly regulated property of the neurite independent of growth cone dynamics. We observe that redistribution of traction in the peripheral domain can reorient the end of the neurite shaft. This suggests a role for off-axis force in growth cone turning and neuronal guidance. PMID:24825441

  10. NeuronGrowth, a software for automatic quantification of neurite and filopodial dynamics from time-lapse sequences of digital images.

    PubMed

    Fanti, Zian; Martinez-Perez, M Elena; De-Miguel, Francisco F

    2011-10-01

    We developed NeuronGrowth, a software for the automatic quantification of extension and retraction of neurites and filopodia, from time-lapse sequences of two-dimensional digital micrographs. NeuronGrowth requires a semiautomatic characterization of individual neurites in a reference frame, which is then used for automatic tracking and measurement of every neurite over the whole image sequence. Modules for sequence alignment, background subtraction, flat field correction, light normalization, and cropping have been integrated to improve the quality of the analysis. Moreover, NeuronGrowth incorporates a deconvolution filter that corrects the shadow-cast effect of differential interference contrast (DIC) images. NeuronGrowth was tested by analyzing the formation of outgrowth patterns by individual leech neurons cultured under two different conditions. Phase contrast images were obtained from neurons plated on CNS homogenates and DIC images were obtained from similar neurons plated on ganglion capsules as substrates. Filopodia were measured from fluorescent growth-cones of chick dorsal root ganglion cells. Quantitative data of neurite extension and retraction obtained by three different users applying NeuronGrowth and two other manually operated software packages were similar. However, NeuronGrowth required less user participation and had a better time performance when compared with the other software packages. NeuronGrowth may be used in general to quantify the dynamics of tubular structures such as blood vessels. NeuronGrowth is a free plug-in for the free software ImageJ and can be downloaded along with a user manual, a troubleshooting section and other information required for its use from http://www.ifc.unam.mx or http://www.ifc.unam.mx/ffm/index.html. PMID:21913334

  11. Silver nanoparticles at sublethal concentrations disrupt cytoskeleton and neurite dynamics in cultured adult neural stem cells.

    PubMed

    Cooper, Robert J; Spitzer, Nadja

    2015-05-01

    Silver nanoparticles (AgNPs) have potent antimicrobial properties at concentrations far below those that cause cytotoxic and genotoxic effects in eukaryotic cells. This property has resulted in the widespread use of AgNPs in consumer products, leading to environmental exposures at sub-lethal levels through ingestion and inhalation. Although the toxicity of AgNPs has been well characterized, effects of environmentally relevant exposures have not been extensively investigated in spite of studies that suggest accumulation of silver in tissues, including brain. To assess the sublethal effects of AgNPs on neural cell function, we used cultured SVZ-NSCs, a model of neurogenesis and neural cells. Throughout life, neural stem cells (NSCs) in the subventricular zone (SVZ) of the lateral ventricles proliferate and migrate via the rostral migratory stream to the olfactory bulb. Once there, they complete differentiation into neurons and glia and integrate into existing circuits. This process of neurogenesis is tightly regulated, and is considered a part of healthy brain function. We found that 1.0 μg/mL AgNP exposure in cultured differentiating NSCs induced the formation of f-actin inclusions, indicating a disruption of actin function. These inclusions did not co-localize with AgNPs, and therefore do not represent sequestered nanoparticles. Further, AgNP exposure led to a reduction in neurite extension and branching in live cells, cytoskeleton-mediated processes vital to neurogenesis. We conclude that AgNPs at sublethal concentrations disrupt actin dynamics in SVZ-NSCs, and that an associated disruption in neurogenesis may contribute to documented deficits in brain function following AgNP exposure. PMID:25952507

  12. Mathematical Relationships between Neuron Morphology and Neurite Growth Dynamics in Drosophila melanogaster Larva Class IV Sensory Neurons

    NASA Astrophysics Data System (ADS)

    Ganguly, Sujoy; Liang, Xin; Grace, Michael; Lee, Daniel; Howard, Jonathon

    The morphology of neurons is diverse and reflects the diversity of neuronal functions, yet the principles that govern neuronal morphogenesis are unclear. In an effort to better understand neuronal morphogenesis we will be focusing on the development of the dendrites of class IV sensory neuron in Drosophila melanogaster. In particular we attempt to determine how the the total length, and the number of branches of dendrites are mathematically related to the dynamics of neurite growth and branching. By imaging class IV neurons during early embryogenesis we are able to measure the change in neurite length l (t) as a function of time v (t) = dl / dt . We found that the distribution of v (t) is well characterized by a hyperbolic secant distribution, and that the addition of new branches per unit time is well described by a Poisson process. Combining these measurements with the assumption that branching occurs with equal probability anywhere along the dendrite we were able to construct a mathematical model that provides reasonable agreement with the observed number of branches, and total length of the dendrites of the class IV sensory neuron.

  13. PAK-PIX interactions regulate adhesion dynamics and membrane protrusion to control neurite outgrowth.

    PubMed

    Santiago-Medina, Miguel; Gregus, Kelly A; Gomez, Timothy M

    2013-03-01

    The roles of P21-activated kinase (PAK) in the regulation of axon outgrowth downstream of extracellular matrix (ECM) proteins are poorly understood. Here we show that PAK1-3 and PIX are expressed in the developing spinal cord and differentially localize to point contacts and filopodial tips within motile growth cones. Using a specific interfering peptide called PAK18, we found that axon outgrowth is robustly stimulated on laminin by partial inhibition of PAK-PIX interactions and PAK function, whereas complete inhibition of PAK function stalls axon outgrowth. Furthermore, modest inhibition of PAK-PIX stimulates the assembly and turnover of growth cone point contacts, whereas strong inhibition over-stabilizes adhesions. Point mutations within PAK confirm the importance of PIX binding. Together our data suggest that regulation of PAK-PIX interactions in growth cones controls neurite outgrowth by influencing the activity of several important mediators of actin filament polymerization and retrograde flow, as well as integrin-dependent adhesion to laminin. PMID:23321640

  14. Triggering of high-speed neurite outgrowth using an optical microheater

    PubMed Central

    Oyama, Kotaro; Zeeb, Vadim; Kawamura, Yuki; Arai, Tomomi; Gotoh, Mizuho; Itoh, Hideki; Itabashi, Takeshi; Suzuki, Madoka; Ishiwata, Shin’ichi

    2015-01-01

    Optical microheating is a powerful non-invasive method for manipulating biological functions such as gene expression, muscle contraction, and cell excitation. Here, we demonstrate its potential usage for regulating neurite outgrowth. We found that optical microheating with a water-absorbable 1,455-nm laser beam triggers directional and explosive neurite outgrowth and branching in rat hippocampal neurons. The focused laser beam under a microscope rapidly increases the local temperature from 36 °C to 41 °C (stabilized within 2 s), resulting in the elongation of neurites by more than 10 μm within 1 min. This high-speed, persistent elongation of neurites was suppressed by inhibitors of both microtubule and actin polymerization, indicating that the thermosensitive dynamics of these cytoskeletons play crucial roles in this heat-induced neurite outgrowth. Furthermore, we showed that microheating induced the regrowth of injured neurites and the interconnection of neurites. These results demonstrate the efficacy of optical microheating methods for the construction of arbitrary neural networks. PMID:26568288

  15. The cytoskeleton and neurite initiation

    PubMed Central

    Flynn, Kevin C

    2013-01-01

    Neurons begin their life as simple spheres, but can ultimately assume an elaborate morphology with numerous, highly arborized dendrites, and long axons. This is achieved via an astounding developmental progression which is dependent upon regulated assembly and dynamics of the cellular cytoskeleton. As neurites emerge out of the soma, neurons break their spherical symmetry and begin to acquire the morphological features that define their structure and function. Neurons regulate their cytoskeleton to achieve changes in cell shape, velocity, and direction as they migrate, extend neurites, and polarize. Of particular importance, the organization and dynamics of actin and microtubules directs the migration and morphogenesis of neurons. This review focuses on the regulation of intrinsic properties of the actin and microtubule cytoskeletons and how specific cytoskeletal structures and dynamics are associated with the earliest phase of neuronal morphogenesis—neuritogenesis. PMID:24002528

  16. Dendrite and Axon Specific Geometrical Transformation in Neurite Development

    PubMed Central

    Mironov, Vasily I.; Semyanov, Alexey V.; Kazantsev, Victor B.

    2016-01-01

    We propose a model of neurite growth to explain the differences in dendrite and axon specific neurite development. The model implements basic molecular kinetics, e.g., building protein synthesis and transport to the growth cone, and includes explicit dependence of the building kinetics on the geometry of the neurite. The basic assumption was that the radius of the neurite decreases with length. We found that the neurite dynamics crucially depended on the relationship between the rate of active transport and the rate of morphological changes. If these rates were in the balance, then the neurite displayed axon specific development with a constant elongation speed. For dendrite specific growth, the maximal length was rapidly saturated by degradation of building protein structures or limited by proximal part expansion reaching the characteristic cell size. PMID:26858635

  17. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    SciTech Connect

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R.

    2011-11-15

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  18. Analysis of slow-onset neurite formation in NG108-15 cells: implications for a unified model of neurite elongation.

    PubMed

    Smalheiser, N R

    1989-01-01

    When undifferentiated NG108-15 cells are plated onto polylysine coated Petri dishes in serum-free medium, they form neurites within 1-4 h if plated in the presence of laminin or 5'-deoxy-5'-methylthioadenosine (rapid-onset neurites). In the absence of such agents, serum-deprived NG108-15 cells extend axon-like neurites onto polylysine over several days; here we characterize the dynamic behavior of this slow-onset outgrowth pattern in detail. Individual cells plated on laminin expressed a gradual multipolar-to-unipolar transition due to rapid-onset neurites becoming remodelled into the appearance of slow-onset neurites. This phenomenon reflected the selective stabilization of certain rapid-onset neurites, along with the restriction of motility to their distal tips. Based upon the properties and interactions of both rapid- and slow-onset neurites in NG108-15 cells, a unified model for neurite formation is presented. PMID:2917412

  19. Neurite development in PC12 cells cultured on nanopillars and nanopores with sizes comparable with filopodia

    PubMed Central

    Haq, Furqan; Anandan, Venkatramani; Keith, Charles; Zhang, Guigen

    2007-01-01

    We investigated the effect of nanoscale topography on neurite development in pheochromocytoma (PC12 cells) by culturing the cells on substrates having nanoscale pillars and pores with sizes comparable with filipodia. We found that cells on nanopillars and nanopores developed fewer and shorter neurites than cells on smooth substrates, and that cells on nanopores developed more and longer neurites than cells on nanopillars. These results suggest that PC12 cells were spatially aware of the difference in the nanoscale structures of the underlying substrates and responded differently in their neurite extension. This finding points to the possibility of using nanoscale topographic features to control neurite development in neurons. PMID:17722518

  20. Polyester with Pendent Acetylcholine-Mimicking Functionalities Promotes Neurite Growth.

    PubMed

    Wang, Shaofei; Jeffries, Eric; Gao, Jin; Sun, Lijie; You, Zhengwei; Wang, Yadong

    2016-04-20

    Successful regeneration of nerves can benefit from biomaterials that provide a supportive biochemical and mechanical environment while also degrading with controlled inflammation and minimal scar formation. Herein, we report a neuroactive polymer functionalized by covalent attachment of the neurotransmitter acetylcholine (Ach). The polymer was readily synthesized in two steps from poly(sebacoyl diglyceride) (PSeD), which previously demonstrated biocompatibility and biodegradation in vivo. Distinct from prior acetylcholine-biomimetic polymers, PSeD-Ach contains both quaternary ammonium and free acetyl moieties, closely resembling native acetylcholine structure. The polymer structure was confirmed via (1)H nuclear magnetic resonance and Fourier-transform infrared spectroscopy. Hydrophilicity, charge, and thermal properties of PSeD-Ach were determined by tensiometer, zetasizer, differential scanning calorimetry, and thermal gravimetric analysis, respectively. PC12 cells exhibited the greatest proliferation and neurite outgrowth on PSeD-Ach and laminin substrates, with no significant difference between these groups. PSeD-Ach yielded much longer neurite outgrowth than the control polymer containing ammonium but no the acetyl group, confirming the importance of the entire acetylcholine-like moiety. Furthermore, PSeD-Ach supports adhesion of primary rat dorsal root ganglions and subsequent neurite sprouting and extension. The sprouting rate is comparable to the best conditions from previous report. Our findings are significant in that they were obtained with acetylcholine-like functionalities in 100% repeating units, a condition shown to yield significant toxicity in prior publications. Moreover, PSeD-Ach exhibited favorable mechanical and degradation properties for nerve tissue engineering application. Humidified PSeD-Ach had an elastic modulus of 76.9 kPa, close to native neural tissue, and could well recover from cyclic dynamic compression. PSeD-Ach showed a gradual in

  1. Rho-associated protein kinase modulates neurite extension by regulating microtubule remodeling and vinculin distribution

    PubMed Central

    Chen, Ke’en; Zhang, Wenbin; Chen, Jing; Li, Sumei; Guo, Guoqing

    2013-01-01

    Rho-associated protein kinase is an essential regulator of cytoskeletal dynamics during the process of neurite extension. However, whether Rho kinase regulates microtubule remodeling or the distribution of adhesive proteins to mediate neurite outgrowth remains unclear. By specifically modulating Rho kinase activity with pharmacological agents, we studied the morpho-dynamics of neurite outgrowth. We found that lysophosphatidic acid, an activator of Rho kinase, inhibited neurite outgrowth, which could be reversed by Y-27632, an inhibitor of Rho kinase. Meanwhile, reorganization of microtubules was noticed during these processes, as indicated by their significant changes in the soma and growth cone. In addition, exposure to lysophosphatidic acid led to a decreased membrane distribution of vinculin, a focal adhesion protein in neurons, whereas Y-27632 recruited vinculin to the membrane. Taken together, our data suggest that Rho kinase regulates rat hippocampal neurite growth and microtubule formation via a mechanism associated with the redistribution of vinculin. PMID:25206623

  2. Interleukin-1 beta and neurotrophin-3 synergistically promote neurite growth in vitro.

    PubMed

    Boato, Francesco; Hechler, Daniel; Rosenberger, Karen; Lüdecke, Doreen; Peters, Eva M; Nitsch, Robert; Hendrix, Sven

    2011-01-01

    Pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) are considered to exert detrimental effects during brain trauma and in neurodegenerative disorders. Consistently, it has been demonstrated that IL-1β suppresses neurotrophin-mediated neuronal cell survival rendering neurons vulnerable to degeneration. Since neurotrophins are also well known to strongly influence axonal plasticity, we investigated here whether IL-1β has a similar negative impact on neurite growth. We analyzed neurite density and length of organotypic brain and spinal cord slice cultures under the influence of the neurotrophins NGF, BDNF, NT-3 and NT-4. In brain slices, only NT-3 significantly promoted neurite density and length. Surprisingly, a similar increase of neurite growth was induced by IL-1β. Additionally, both factors increased the number of brain slices displaying maximal neurite growth. Furthermore, the co-administration of IL-1β and NT-3 significantly increased the number of brain slices displaying maximal neurite growth compared to single treatments. These data indicate that these two factors synergistically stimulate two distinct aspects of neurite outgrowth, namely neurite density and neurite length from acute organotypic brain slices. PMID:22200088

  3. Interleukin-1 beta and neurotrophin-3 synergistically promote neurite growth in vitro

    PubMed Central

    2011-01-01

    Pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) are considered to exert detrimental effects during brain trauma and in neurodegenerative disorders. Consistently, it has been demonstrated that IL-1β suppresses neurotrophin-mediated neuronal cell survival rendering neurons vulnerable to degeneration. Since neurotrophins are also well known to strongly influence axonal plasticity, we investigated here whether IL-1β has a similar negative impact on neurite growth. We analyzed neurite density and length of organotypic brain and spinal cord slice cultures under the influence of the neurotrophins NGF, BDNF, NT-3 and NT-4. In brain slices, only NT-3 significantly promoted neurite density and length. Surprisingly, a similar increase of neurite growth was induced by IL-1β. Additionally, both factors increased the number of brain slices displaying maximal neurite growth. Furthermore, the co-administration of IL-1β and NT-3 significantly increased the number of brain slices displaying maximal neurite growth compared to single treatments. These data indicate that these two factors synergistically stimulate two distinct aspects of neurite outgrowth, namely neurite density and neurite length from acute organotypic brain slices. PMID:22200088

  4. The influence of ensheathing cells on olfactory receptor cell neurite outgrowth in vitro.

    PubMed

    Kafitz, K W; Greer, C A

    1998-11-30

    We previously reported that laminin substrates increased primary (1 degree) neurite outgrowth from olfactory receptor cells (ORCs) in vitro. To further explore mechanisms underlying the outgrowth of ORC neurites, we have cocultured ORCs with the ensheathing cells (ENSH) from the olfactory nerve. ORCs were plated either: (i) directly on monolayers of ENSH (prepared with minor modifications as reported by Doucette and Devon, or (ii) on coverslips suspended above the ENSH monolayer to investigate diffusible trophic influences of ENSH. In addition, ORCs were cocultured with either olfactory bulb glia (OBG) or hippocampal astrocytes (HG) or grown on either laminin (LN) substrates or poly-L-lysine (PLL) controls. The length of ORC neurites was determined after 48 hr in vitro. Immunocytochemical characterization of the ENSH cultures for p75 nerve growth factor (NGF) receptor and glial fibrillary acidic protein (GFAP) revealed that those cultures contained more than 80% ENSH. In OBG cultures approximately 10% and in HG cultures no cells with ENSH characteristics were found. All cells with ENSH characteristics were also LN-immunoreactive. After 48 hr in culture ORCs had the longest 1 degree neurites when they were cocultured with ENSH. No significant differences in the 1 degree neurite length were found comparing ORCs grown directly on ENSH and ORCs physically separated from ENSH. ORCs cultured on HG and on EHS-LN showed no significant differences in the ORC 1 degree neurite length, but on both substrates the ORC 1 degree neurites were significantly shorter than on ENSH. The length of the ORC secondary neurites did not vary significantly in the different culture conditions. Our results suggest that while LN appears to contribute to ORC neurite extension, additional diffusible factors released from ENSH are likely to be further determinants of neurite outgrowth. Because the OBG and HG cocultures did not influence ORC neurite outgrowth as significantly as did the ENSH, it

  5. HMG-CoA reductase inhibition causes neurite loss by interfering with geranylgeranylpyrophosphate synthesis.

    PubMed

    Schulz, Joachim G; Bösel, Julian; Stoeckel, Magali; Megow, Dirk; Dirnagl, Ulrich; Endres, Matthias

    2004-04-01

    To determine whether neurite outgrowth depends upon the mevalonate pathway, we blocked mevalonate synthesis in nerve growth factor-treated PC12 cells or primary cortical neurones with atorvastatin, a 3-hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and substituted different intermediates of the mevalonate pathway. We show that HMG-CoA reductase inhibition causes a profound reduction of neurite length, neurite loss and ultimatively cell death in undifferentiated and pre-differentiated PC12 cells and also in rat primary cortical neurones. Geranylgeranylpyrophosphate, but not farnesylpyrophosphate, squalene or cholesterol, completely compensated for the lack of mevalonate. Our data indicate that, under HMG-CoA reductase inhibition, geranylgeranylpyrophosphate rather than farnesylpyrophosphate or cholesterol is critical for neurite outgrowth and/or maintenance. Loss of neurites is an early manifestation of various neurodegenerative disorders, and dysfunction of isoprenylation might play a role in their pathogenesis. PMID:15030386

  6. Controlling Neurite Outgrowth with Patterned Substrates

    PubMed Central

    Yang, In Hong; Co, Carlos C.; Ho, Chia-Chi

    2011-01-01

    In vivo, neurons form neurites, one of which develops into the axon while others become dendrites. While this neuritogenesis process is well programmed in vivo, there are limited methods to control the number and location of neurite extension in vitro. Here we report a method to control neuritogenesis by confining neurons in specific regions using cell resistant poly(oligoethyleneglycol methacrylate-co-methacrylic acid (OEGMA-co-MA)) or poly(ethyleneglycol-block-lactic acid) PEG-PLA. Line patterned substrates reduce multiple extension of neurites and stimulate bi-directional neurite budding for PC12 and cortical neurons. PC12 cells on 20 and 30 µm line patterns extended one neurite in each direction along the line pattern while cortical neuron on 20 and 30 µm line patterns extended one or two neurites in each direction along the line pattern. Statistical analysis of neurite lengths revealed that PC12 cells and cortical neurons on line patterns extend longer neurites. The ability to guide formation of neurites on patterned substrates is useful for generating neural networks and promoting neurite elongation. PMID:21484989

  7. Guidance of dorsal root ganglion neurites and Schwann cells by isolated Schwann cell topography on poly(dimethyl siloxane) conduits and films

    NASA Astrophysics Data System (ADS)

    Richardson, J. A.; Rementer, C. W.; Bruder, Jan M.; Hoffman-Kim, D.

    2011-08-01

    Biomimetic replicas of cellular topography have been utilized to direct neurite outgrowth. Here, we cultured postnatal rat dorsal root ganglion (DRG) explants in the presence of Schwann cell (SC) topography to determine the influence of SC topography on neurite outgrowth. Four distinct poly(dimethyl siloxane) conduits were fabricated within which DRG explants were cultured. To determine the contribution of SC topographical features to neurite guidance, the extent of neurite outgrowth into unpatterned conduits, conduits with randomly oriented SC replicas, and conduits with SC replicas parallel or perpendicular to the conduit long axis was measured. Neurite directionality and outgrowth from DRG were also quantified on two-dimensional SC replicas with orientations corresponding to the four conduit conditions. Additionally, live SC migration and neurite extension from DRG on SC replicas were examined as a first step toward quantification of the interactions between live SC and navigating neurites on SC replicas. DRG neurite outgrowth and morphology within conduits and on two-dimensional SC replicas were directed by the underlying SC topographical features. Maximal neurite outgrowth and alignment to the underlying features were observed into parallel conduits and on parallel two-dimensional substrates, whereas the least extent of outgrowth was observed into perpendicular conduits and on perpendicular two-dimensional replica conditions. Additionally, neurites on perpendicular conditions turned to extend along the direction of underlying SC topography. Neurite outgrowth exceeded SC migration in the direction of the underlying anisotropic SC replica after two days in culture. This finding confirms the critical role that SC have in guiding neurite outgrowth and suggests that the mechanism of neurite alignment to SC replicas depends on direct contact with cellular topography. These results suggest that SC topographical replicas may be used to direct and optimize neurite

  8. Intracellular calcium and cyclic nucleotide levels modulate neurite guidance by microtopographical substrate features.

    PubMed

    Li, Shufeng; Tuft, Bradley; Xu, Linjing; Polacco, Marc; Clarke, Joseph C; Guymon, C Allan; Hansen, Marlan R

    2016-08-01

    Micro- and nanoscale surface features have emerged as potential tools to direct neurite growth into close proximity with next generation neural prosthesis electrodes. However, the signaling events underlying the ability of growth cones to respond to topographical features remain largely unknown. Accordingly, this study probes the influence of [Ca(2+) ]i and cyclic nucleotide levels on the ability of neurites from spiral ganglion neurons (SGNs) to precisely track topographical micropatterns. Photopolymerization and photomasking were used to generate micropatterned methacrylate polymer substrates. Dissociated SGN cultures were plated on the micropatterned surfaces. Calcium influx and release from internal stores were manipulated by elevating extracellular K(+) , maintenance in calcium-free media, or bath application of various calcium channel blockers. Cyclic nucleotide activity was increased by application of cpt-cAMP or 8-Br-cGMP. Elevation of [Ca(2+) ]i by treatment of cultures with elevated potassium reduced neurite alignment to physical microfeatures. Maintenance of cultures in Ca(2+) -free medium or treatment with the non-selective voltage-gated calcium channel blocker cadmium or L-type Ca(2+) channel blocker nifedipine did not signficantly alter SGN neurite alignment. By contrast, ryanodine or xestospongin C, which block release of internal calcium stores via ryanodine-sensitive channels or inositol-1,4,5-trisphosphate receptors respectively, each significantly decreased neurite alignment. Cpt-cAMP significantly reduced neurite alignment while 8-Br-cGMP significantly enhanced neurite alignment. Manipulation of [Ca(2+) ]i or cAMP levels significantly disrupts neurite guidance while elevation of cGMP levels increases neurite alignment. The results suggest intracellular signaling pathways similar to those recruited by chemotactic cues are involved in neurite guidance by topographical features. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2037

  9. Magnetotail dynamics under isobaric constraints

    NASA Technical Reports Server (NTRS)

    Birn, Joachim; Schindler, Karl; Janicke, Lutz; Hesse, Michael

    1994-01-01

    Using linear theory and nonlinear MHD simulations, we investigate the resistive and ideal MHD stability of two-dimensional plasma configurations under the isobaric constraint dP/dt = 0, which in ideal MHD is equivalent to conserving the pressure function P = P(A), where A denotes the magnetic flux. This constraint is satisfied for incompressible modes, such as Alfven waves, and for systems undergoing energy losses. The linear stability analysis leads to a Schroedinger equation, which can be investigated by standard quantum mechanics procedures. We present an application to a typical stretched magnetotail configuration. For a one-dimensional sheet equilibrium characteristic properties of tearing instability are rediscovered. However, the maximum growth rate scales with the 1/7 power of the resistivity, which implies much faster growth than for the standard tearing mode (assuming that the resistivity is small). The same basic eigen-mode is found also for weakly two-dimensional equilibria, even in the ideal MHD limit. In this case the growth rate scales with the 1/4 power of the normal magnetic field. The results of the linear stability analysis are confirmed qualitatively by nonlinear dynamic MHD simulations. These results suggest the interesting possibility that substorm onset, or the thinning in the late growth phase, is caused by the release of a thermodynamic constraint without the (immediate) necessity of releasing the ideal MHD constraint. In the nonlinear regime the resistive and ideal developments differ in that the ideal mode does not lead to neutral line formation without the further release of the ideal MHD constraint; instead a thin current sheet forms. The isobaric constraint is critically discussed. Under perhaps more realistic adiabatic conditions the ideal mode appears to be stable but could be driven by external perturbations and thus generate the thin current sheet in the late growth phase, before a nonideal instability sets in.

  10. Charge-balanced biphasic electrical stimulation inhibits neurite extension of spiral ganglion neurons.

    PubMed

    Shen, Na; Liang, Qiong; Liu, Yuehong; Lai, Bin; Li, Wen; Wang, Zhengmin; Li, Shufeng

    2016-06-15

    Intracochlear application of exogenous or transgenic neurotrophins, such as neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF), could promote the resprouting of spiral ganglion neuron (SGN) neurites in deafened animals. These resprouting neurites might reduce the gap between cochlear implant electrodes and their targeting SGNs, allowing for an improvement of spatial resolution of electrical stimulation. This study is to investigate the impact of electrical stimulation employed in CI on the extension of resprouting SGN neurites. We established an in vitro model including the devices delivering charge-balanced biphasic electrical stimulation, and spiral ganglion (SG) dissociated culture treated with BDNF and NT-3. After electrical stimulation with varying durations and intensities, we quantified neurite lengths and Schwann cell densities in SG cultures. Stimulations that were greater than 50μA or longer than 8h significantly decreased SG neurite length. Schwann cell density under 100μA electrical stimulation for 48h was significantly lower compared to that in non-stimulated group. These electrical stimulation-induced decreases of neurite extension and Schwann cell density were attenuated by various types of voltage-dependent calcium channel (VDCC) blockers, or completely prevented by their combination, cadmium or calcium-free medium. Our study suggested that charge-balanced biphasic electrical stimulation inhibited the extension of resprouting SGN neurites and decreased Schwann cell density in vitro. Calcium influx through multiple types of VDCCs was involved in the electrical stimulation-induced inhibition. PMID:27163199

  11. Neurite Outgrowth on Nanofiber Scaffolds with Different Orders, Structures, and Surface Properties

    PubMed Central

    Xie, Jingwei; MacEwan, Matthew R.; Li, Xiaoran; Sakiyama-Elbert, Shelly E.; Xia, Younan

    2009-01-01

    Electrospun nanofibers can be readily assembled into various types of scaffolds for applications in neural tissue engineering. The objective of this study is to examine and understand the unique patterns of neurite outgrowth from primary dorsal root ganglia (DRG) cultured on scaffolds of electrospun nanofibers having different orders, structures, and surface properties. We found that the neurites extended radially outward from the DRG main body without specific directionality when cultured on a nonwoven mat of randomly oriented nanofibers. In contrast, the neurites preferentially extended along the long axis of fiber when cultured on a parallel array of aligned nanofibers. When seeded at the border between regions of aligned and random nanofibers, the same DRG simultaneously expressed aligned and random neurite fields in response to the underlying nanofibers. When cultured on a double-layered scaffold where the nanofibers in each layer were aligned along a different direction, the neurites were found to be dependent on the fiber density in both layers. This bi-axial pattern clearly demonstrates that neurite outgrowth can be influenced by nanofibers in different layers of a scaffold, rather than the topmost layer only. Taken together, these results will provide valuable information pertaining to the design of nanofiber scaffolds for neuroregenerative applications, as well as the effects of topology on neurite outgrowth, growth cone guidance, and axonal regeneration. PMID:19397333

  12. Semi-automatic quantification of neurite fasciculation in high-density neurite images by the Neurite Directional Distribution Analysis (NDDA)

    PubMed Central

    Hopkins, Amy M; Wheeler, Brandon; Staii, Cristian; Kaplan, David L.; Atherton, Timothy J.

    2014-01-01

    Background Bundling of neurite extensions occur during nerve development and regeneration. Understanding the factors that drive neurite bundling is important for designing biomaterials for nerve regeneration toward the innervation target and preventing nociceptive collateral sprouting. High-density neuron cultures including dorsal root ganglia explants are employed for in vitro screening of biomaterials designed to control directional outgrowth. Although some semiautomated image processing methods exist for quantification of neurite outgrowth, methods to quantify axonal fasciculation in terms of direction of neurite outgrowth are lacking. New Method This work presents a semi-automated program to analyze micrographs of high-density neurites; the program aims to quantify axonal fasciculation by determining the orientational distribution function of the tangent vectors of the neurites and calculating its Fourier series coefficients (‘c’ values). Results We found that neurite directional distribution analysis (NDDA) of fasciculated neurites yielded ‘c’ values of ≥ ~0.25 whereas branched outgrowth led to statistically significant lesser values of <~0.2. The ‘c’ values correlated directly to the width of neurite bundles and indirectly to the number of branching points. Comparison with Existing Methods Information about the directional distribution of outgrowth is lost in simple counting methods or achieved laboriously through manual analysis. The NDDA supplements previous quantitative analyses of axonal bundling using a vector-based approach that captures new information about the directionality of outgrowth. Conclusion The NDDA is a valuable addition to open source image processing tools available to biomedical researchers offering a robust, precise approach to quantification of imaged features important in tissue development, disease, and repair. PMID:24680908

  13. Immobilized laminin concentration gradients on electrospun fiber scaffolds for controlled neurite outgrowth.

    PubMed

    Zander, Nicole E; Beebe, Thomas P

    2014-03-01

    Neuronal process growth is guided by extrinsic environmental cues such as extracellular matrix (ECM) proteins. Recent reports have described that the growth cone extension is superior across gradients of the ECM protein laminin compared to growth across uniformly distributed laminin. In this work, the authors have prepared gradients of laminin on aligned electrospun nanofibers for use as substrates for neuronal growth. The substrates therefore presented both topographical and chemical guidance cues. Step gradients were prepared by the controlled robotic immersion of plasma-treated polycaprolactone fibers reacted with N-hydroxysuccinimide into the protein solution. The gradients were analyzed using x-ray photoelectron spectroscopy and confocal laser scanning microscopy. Gradients with a dynamic range of protein concentrations were successfully generated and neurite outgrowth was evaluated using neuronlike pheochromocytoma cell line 12 (PC12) cells. After 10 days of culture, PC12 neurite lengths varied from 32.7 ± 14.2 μm to 76.3 ± 9.1 μm across the protein concentration gradient. Neurite lengths at the highest concentration end of the gradient were significantly longer than neurite lengths observed for cells cultured on samples with uniform protein coverage. Gradients were prepared both in the fiber direction and transverse to the fiber direction. Neurites preferentially aligned with the fiber direction in both cases indicating that fiber alignment has a more dominant role in controlling neurite orientation, compared to the chemical gradient. PMID:24739010

  14. Self-aligned Schwann cell monolayers demonstrate an inherent ability to direct neurite outgrowth

    NASA Astrophysics Data System (ADS)

    Seggio, A. M.; Narayanaswamy, A.; Roysam, B.; Thompson, D. M.

    2010-08-01

    In vivo nerve guidance channel studies have identified Schwann cell (SC) presence as an integral factor in axonal number and extension in an injury site, and in vitro studies have provided evidence that oriented SCs can direct neurite outgrowth. However, traditional methods used to create oriented SC monolayers (e.g. micropatterns/microtopography) potentially introduce secondary guidance cues to the neurons that are difficult to de-couple. Although SCs expanded on uniform laminin-coated coverslips lack a global orientation, the monolayers contain naturally formed regions of locally oriented cells that can be used to investigate SC-mediated neurite guidance. In this work, novel image analysis techniques have been developed to quantitatively assess local neurite orientation with respect to the underlying regional orientation of the Schwann cell monolayer. Results confirm that, in the absence of any secondary guidance cues, a positive correlation exists between neurite outgrowth and regional orientation of the SC monolayer. Thus, SCs alone possess an inherent ability to direct neurite outgrowth, and expansion of the co-culture-based quantitative method described can be used to further deconstruct specific biomolecular mechanisms of neurite guidance.

  15. Sonic hedgehog stimulates neurite outgrowth in a mechanical stretch model of reactive-astrogliosis

    PubMed Central

    Berretta, Antonio; Gowing, Emma K.; Jasoni, Christine L.; Clarkson, Andrew N.

    2016-01-01

    Although recovery following a stroke is limited, undamaged neurons under the right conditions can establish new connections and take on-board lost functions. Sonic hedgehog (Shh) signaling is integral for developmental axon growth, but its role after injury has not been fully examined. To investigate the effects of Shh on neuronal sprouting after injury, we used an in vitro model of glial scar, whereby cortical astrocytes were mechanically traumatized to mimic reactive astrogliosis observed after stroke. This mechanical trauma impaired neurite outgrowth from post-natal cortical neurons plated on top of reactive astrocytes. Addition of Shh to the media, however, resulted in a concentration-dependent increase in neurite outgrowth. This response was inhibited by cyclopamine and activated by oxysterol 20(S)-hydroxycholesterol, both of which modulate the activity of the Shh co-receptor Smoothened (Smo), demonstrating that Shh-mediated neurite outgrowth is Smo-dependent. In addition, neurite outgrowth was not associated with an increase in Gli-1 transcription, but could be inhibited by PP2, a selective inhibitor of Src family kinases. These results demonstrate that neurons exposed to the neurite growth inhibitory environment associated with a glial scar can be stimulated by Shh, with signaling occurring through a non-canonical pathway, to overcome this suppression and stimulate neurite outgrowth. PMID:26902390

  16. SOCS3 induces neurite differentiation and promotes neuronal cell survival.

    PubMed

    Mishra, Kanchan Kumar; Gupta, Sakshi; Banerjee, Kakoli

    2016-06-01

    Cytokines and growth factors play an important role in neuronal survival as well as cell death. The family of suppressors of cytokine signalling (SOCS) proteins, which includes SOCS1-7 and cytokine-induced suppressor (CIS), has been shown to act as negative regulators of cytokine-induced signalling. In this report, we highlight the role of SOCS3 in regulating neuronal differentiation and survival. We observed increased SOCS3 expression upon differentiation of PC12 cells as well as neural stem cells. SOCS3 overexpression upregulated differentiation of both neural stem cells and PC12 cells even in the absence of NGF, as evidenced by enhanced neurite outgrowth and upregulation of GAP43, marker associated with neurite outgrowth. siRNA-mediated silencing of SOCS3 confirmed the potential role of SOCS3 in neuritogenesis. We observed that, SOCS3-induced neurite differentiation was mediated via the PI3 kinase pathway. Another interesting observation was that SOCS3 overexpression promoted neuronal cell survival under H2 O2 -mediated stress indicating its fundamental role in cell survival. In conclusion, our results indicate that SOCS3 promotes differentiation and survival of neural cells and could be potentially useful in future therapy for treatment of neurodegenerative disorders. © 2016 IUBMB Life, 68(6):468-476, 2016. PMID:27118613

  17. Olfactory ensheathing cell-neurite alignment enhances neurite outgrowth in scar-like cultures

    PubMed Central

    Khankan, Rana R.; Wanner, Ina B.; Phelps, Patricia E.

    2015-01-01

    The regenerative capacity of the adult CNS neurons after injury is strongly inhibited by the spinal cord lesion site environment that is composed primarily of the reactive astroglial scar and invading meningeal fibroblasts. Olfactory ensheathing cell (OEC) transplantation facilitates neuronal survival and functional recovery after a complete spinal cord transection, yet the mechanisms by which this recovery occurs remain unclear. We used a unique multicellular scar-like culture model to test if OECs promote neurite outgrowth in growth inhibitory areas. Astrocytes were mechanically injured and challenged by meningeal fibroblasts to produce key inhibitory elements of a spinal cord lesion. Neurite outgrowth of postnatal cerebral cortical neurons was assessed on three substrates: quiescent astrocyte control cultures, reactive astrocyte scar-like cultures, and scar-like cultures with OECs. Initial results showed that OECs enhanced total neurite outgrowth of cortical neurons in a scar-like environment by 60%. We then asked if the neurite growth-promoting properties of OECs depended on direct alignment between neuronal and OEC processes. Neurites that aligned with OECs were nearly three times longer when they grew on inhibitory meningeal fibroblast areas and twice as long on reactive astrocyte zones compared to neurites not associated with OECs. Our results show that OECs can independently enhance neurite elongation and that direct OEC-neurite cell contact can provide a permissive substrate that overcomes the inhibitory nature of the reactive astrocyte scar border and the fibroblast-rich spinal cord lesion core. PMID:25863021

  18. Behavior of soil anchors under dynamic loads

    SciTech Connect

    Picornell, M.; Olague, B.

    1997-07-01

    Helical anchors placed in a cohesionless soil in a laboratory setting were tested under static and dynamic loads. The dynamic tests were performed after subjecting the anchors to a seating load. The dynamic load had an intensity that changed in sinusoidal fashion and was superimposed to the static seating loads. Although, the anchors have a static pull-out capacity, when the dynamic loads are applied the anchor experiences additional deformations for each load cycle. The deformations per cycle are initially high but then decrease to a nearly constant rate. Eventually, the constant rate increases suddenly accelerating until failure. This failure can take place even at small fractions of the static pull-out capacity. The rate of deformation per load cycle is found to increase for larger seating loads and for larger dynamic pulsating loads. The results of this study shows that the designer can only adjust loads to decrease the deformation rate to suit the design life of the structure.

  19. Strength of concrete structures under dynamic loading

    NASA Astrophysics Data System (ADS)

    Kumpyak, O. G.; Galyautdinov, Z. R.; Kokorin, D. N.

    2016-01-01

    The use of elastic supports is one the efficient methods of decreasing the dynamic loading. The paper describes the influence of elastic supports on the stress-strain state of steel concrete structures exposed to one-time dynamic loading resulting in failure. Oblique bending beams on elastic supports and their elastic, elastoplastic, and elastoplastic consolidation behavior are considered in this paper. For numerical calculations the developed computer program is used based on the finite element method. Research findings prove high efficiency of elastic supports under dynamic loading conditions. The most effective behavior of elastic supports is demonstrated at the elastoplastic stage. A good agreement is observed between the theoretical and experimental results.

  20. MECHANICS OF CRACK BRIDGING UNDER DYNAMIC LOADS

    SciTech Connect

    N. SRIDHAR; ET AL

    2001-02-01

    A bridging law for fiber reinforced composites under dynamic crack propagation conditions has been derived. Inertial effects in the mechanism of fiber pullout during dynamic propagation of a bridged crack are critically examined for the first time. By reposing simple shear lag models of pullout as problems of dynamic wave propagation, the effect of the frictional coupling between the fibers and the matrix is accounted for in a fairly straightforward way. The solutions yield the time-dependent relationship between the crack opening displacement and the bridging traction. Engineering criteria and the role of material and geometrical parameters for significant inertial effects are identified.

  1. Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients’ neurons

    PubMed Central

    Havlicek, Steven; Kohl, Zacharias; Mishra, Himanshu K.; Prots, Iryna; Eberhardt, Esther; Denguir, Naime; Wend, Holger; Plötz, Sonja; Boyer, Leah; Marchetto, Maria C.N.; Aigner, Stefan; Sticht, Heinrich; Groemer, Teja W.; Hehr, Ute; Lampert, Angelika; Schlötzer-Schrehardt, Ursula; Winkler, Jürgen; Gage, Fred H.; Winner, Beate

    2014-01-01

    The hereditary spastic paraplegias (HSPs) are a heterogeneous group of motorneuron diseases characterized by progressive spasticity and paresis of the lower limbs. Mutations in Spastic Gait 4 (SPG4), encoding spastin, are the most frequent cause of HSP. To understand how mutations in SPG4 affect human neurons, we generated human induced pluripotent stem cells (hiPSCs) from fibroblasts of two patients carrying a c.1684C>T nonsense mutation and from two controls. These SPG4 and control hiPSCs were able to differentiate into neurons and glia at comparable efficiency. All known spastin isoforms were reduced in SPG4 neuronal cells. The complexity of SPG4 neurites was decreased, which was paralleled by an imbalance of axonal transport with less retrograde movement. Prominent neurite swellings with disrupted microtubules were present in SPG4 neurons at an ultrastructural level. While some of these swellings contain acetylated and detyrosinated tubulin, these tubulin modifications were unchanged in total cell lysates of SPG4 neurons. Upregulation of another microtubule-severing protein, p60 katanin, may partially compensate for microtubuli dynamics in SPG4 neurons. Overexpression of the M1 or M87 spastin isoforms restored neurite length, branching, numbers of primary neurites and reduced swellings in SPG4 neuronal cells. We conclude that neurite complexity and maintenance in HSP patient-derived neurons are critically sensitive to spastin gene dosage. Our data show that elevation of single spastin isoform levels is sufficient to restore neurite complexity and reduce neurite swellings in patient cells. Furthermore, our human model offers an ideal platform for pharmacological screenings with the goal to restore physiological spastin levels in SPG4 patients. PMID:24381312

  2. Applied electric field enhances DRG neurite growth: influence of stimulation media, surface coating and growth supplements

    NASA Astrophysics Data System (ADS)

    Wood, Matthew D.; Willits, Rebecca Kuntz

    2009-08-01

    Electrical therapies have been found to aid repair of nerve injuries and have been shown to increase and direct neurite outgrowth during stimulation. This enhanced neural growth existed even after the electric field (EF) or stimulation was removed, but the factors that may influence the enhanced growth, such as stimulation media or surface coating, have not been fully investigated. This study characterized neurite outgrowth and branching under various conditions: EF magnitude and application time, ECM surface coating, medium during EF application and growth supplements. A uniform, low-magnitude EF (24 or 44 V m-1) was applied to dissociated chick embryo dorsal root ganglia seeded on collagen or laminin-coated surfaces. During the growth period, cells were either exposed to NGF or N2, and during stimulation cells were exposed to either unsupplemented media (Ca2+) or PBS (no Ca2+). Parallel controls for each experiment included cells exposed to the chamber with no stimulation and cells remaining outside the chamber. After brief electrical stimulation (10 min), neurite length significantly increased 24 h after application for all conditions studied. Of particular interest, increased stimulation time (10-100 min) further enhanced neurite length on laminin but not on collagen surfaces. Neurite branching was not affected by stimulation on any surface, and no preferential growth of neurites was noted after stimulation. Overall, the results of this report suggest that short-duration electric stimulation is sufficient to enhance neurite length under a variety of conditions. While further data are needed to fully elucidate a mechanism for this increased growth, these data suggest that one focus of those investigations should be the interaction between the growth cone and the substrata.

  3. Applied electric field enhances DRG neurite growth: influence of stimulation media, surface coating and growth supplements.

    PubMed

    Wood, Matthew D; Willits, Rebecca Kuntz

    2009-08-01

    Electrical therapies have been found to aid repair of nerve injuries and have been shown to increase and direct neurite outgrowth during stimulation. This enhanced neural growth existed even after the electric field (EF) or stimulation was removed, but the factors that may influence the enhanced growth, such as stimulation media or surface coating, have not been fully investigated. This study characterized neurite outgrowth and branching under various conditions: EF magnitude and application time, ECM surface coating, medium during EF application and growth supplements. A uniform, low-magnitude EF (24 or 44 V m(-1)) was applied to dissociated chick embryo dorsal root ganglia seeded on collagen or laminin-coated surfaces. During the growth period, cells were either exposed to NGF or N2, and during stimulation cells were exposed to either unsupplemented media (Ca(2+)) or PBS (no Ca(2+)). Parallel controls for each experiment included cells exposed to the chamber with no stimulation and cells remaining outside the chamber. After brief electrical stimulation (10 min), neurite length significantly increased 24 h after application for all conditions studied. Of particular interest, increased stimulation time (10-100 min) further enhanced neurite length on laminin but not on collagen surfaces. Neurite branching was not affected by stimulation on any surface, and no preferential growth of neurites was noted after stimulation. Overall, the results of this report suggest that short-duration electric stimulation is sufficient to enhance neurite length under a variety of conditions. While further data are needed to fully elucidate a mechanism for this increased growth, these data suggest that one focus of those investigations should be the interaction between the growth cone and the substrata. PMID:19494423

  4. Pure neuritic leprosy: Current status and relevance.

    PubMed

    Rao, P Narasimha; Suneetha, Sujai

    2016-01-01

    Pure neuritic leprosy has always been an enigma due to its clinical and management ambiguities. Although only the Indian Association of Leprologist's classification recognizes 'pure neuritic leprosy' as a distinct sub group of leprosy, cases nonetheless are reported from various countries of Asia, Africa, South America and Europe, indicating its global relevance. It is important to maintain pure neuritic leprosy as a subgroup as it constitutes a good percentage of leprosy cases reported from India, which contributes to more than half of global leprosy numbers. Unfortunately, a high proportion of these patients present with Grade 2 disability at the time of initial reporting itself due to the early nerve involvement. Although skin lesions are absent by definition, when skin biopsies were performed from the skin along the distribution of the affected nerve, a proportion of patients demonstrated leprosy pathology, revealing sub-clinical skin involvement. In addition on follow-up, skin lesions are noted to develop in up to 20% of pure neuritic leprosy cases, indicating its progression to manifest cutaneous disease. Over the decades, the confirmation of diagnosis of pure neuritic leprosy has been subjective, however, with the arrival and use of high-resolution ultrasonography (HRUS) for nerve imaging, we have a tool not only to objectively measure and record the nerve thickening but also to assess the morphological alterations in the nerve including echo texture, fascicular pattern and vascularity. Management of pure neuritic leprosy requires multidrug therapy along with appropriate dose of systemic corticosteroids, for both acute and silent neuritis. Measures for pain relief, self-care of limbs and physiotherapy are important to prevent as well as manage disabilities in this group of patients. PMID:27088926

  5. Neurite outgrowth enhancement by jiadifenolide: possible targets.

    PubMed

    Shenvi, R A

    2016-04-01

    Covering: 1860-2016A mechanistic link may exist between convulsant plant substances typified by picrotoxinin, and 'neurotrophic' sesquiterpenes like jiadifenolide. Picrotoxinin elicits convulsion by anion blockade of the Cys-loop family of neurotransmitter-gated ion channels. These same receptors mediate neuronal development and neurite outgrowth prior to synapse formation. Due to its structural homology with picrotoxin and anisatin, it is possible that jiadifenolide enhances NGF-stimulated neurite outgrowth by modulation of the Cys-loop family of receptors. PMID:26891462

  6. Differential Intensity-dependent Effects of Magnetic Stimulation on the Longest Neurites and Shorter Dendrites in Neuroscreen-1 Cells

    PubMed Central

    Lin, Ching-Yi; Huang, Whitney J.; Li, Kevin; Swanson, Roy; Cheung, Brian; Lin, Vernon W.; Lee, Yu-Shang

    2015-01-01

    OBJECTIVE Magnetic stimulation (MS) is a potential treatment for neuropsychiatric disorders. This study investigates whether MS-regulated neuronal activity can translate to specific changes in neuronal arborization and thus regulate synaptic activity and function. APPROACH To test our hypotheses, we examined the effects of MS on neurite growth of Neuroscreen-1 (NS-1) cells over pulse frequencies of 1, 5 and 10 Hz at field intensities controlled by machine output (MO). Cells were treated with either 30% or 40% MO and received either maximal or minimal MS-induced current-density. Due to the nature of circular MS coils, the center region of the gridded coverslip (zone 1) received minimal (~5%) electromagnetic current density while the remaining area (zone 2) received maximal (~95%) current density. Plated NS-1 cells were exposed to MS twice per day for 3 days and then evaluated for length and number of neurites and expression of brain-derived neurotrophic factor (BDNF). MAIN RESULTS We show that MS dramatically affects the growth of the longest neurites (axon-like) but does not significantly affect the growth of shorter neurites (dendrite-like). Also, MS-induced changes in the longest neurite growth were most evident in zone 1, but not in zone 2. MS effects were intensity-dependent and were most evident in the bolstering of the longest neurite outgrowth, mainly seen in the 10 Hz MS group. Furthermore, we found that MS-increased BDNF expression and secretion was also frequency-dependent. Taken together, our results show that MS exerts distinct effects when different frequencies and intensities are applied to the neuritic compartments (longest neurite versus shorter dendrite(s)) of NS-1 cells. SIGNIFICANCE These findings support the concept that MS increases BDNF expression and signaling, which sculpts longest neurite arborization and connectivity by which neuronal activity is regulated. Understanding the mechanisms underlying MS is crucial for efficiently incorporating

  7. Differential intensity-dependent effects of magnetic stimulation on the longest neurites and shorter dendrites in neuroscreen-1 cells

    NASA Astrophysics Data System (ADS)

    Lin, Ching-Yi; Huang, Whitney J.; Li, Kevin; Swanson, Roy; Cheung, Brian; Lin, Vernon W.; Lee, Yu-Shang

    2015-04-01

    Objective. Magnetic stimulation (MS) is a potential treatment for neuropsychiatric disorders. This study investigates whether MS-regulated neuronal activity can translate to specific changes in neuronal arborization and thus regulate synaptic activity and function. Approach. To test our hypotheses, we examined the effects of MS on neurite growth of neuroscreen-1 (NS-1) cells over the pulse frequencies of 1, 5 and 10 Hz at field intensities controlled via machine output (MO). Cells were treated with either 30% or 40% MO. Due to the nature of circular MS coils, the center region of the gridded coverslip (zone 1) received minimal (∼5%) electromagnetic current density while the remaining area (zone 2) received maximal (∼95%) current density. Plated NS-1 cells were exposed to MS twice per day for three days and then evaluated for length and number of neurites and expression of brain-derived neurotrophic factor (BDNF). Main results. We show that MS dramatically affects the growth of the longest neurites (axon-like) but does not significantly affect the growth of shorter neurites (dendrite-like). Also, MS-induced changes in the longest neurite growth were most evident in zone 1, but not in zone 2. MS effects were intensity-dependent and were most evident in bolstering longest neurite outgrowth, best seen in the 10 Hz MS group. Furthermore, we found that MS-increased BDNF expression and secretion was also frequency-dependent. Taken together, our results show that MS exerts distinct effects when different frequencies and intensities are applied to the neuritic compartments (longest neurite versus shorter dendrite(s)) of NS-1 cells. Significance. These findings support the concept that MS increases BDNF expression and signaling, which sculpts longest neurite arborization and connectivity by which neuronal activity is regulated. Understanding the mechanisms underlying MS is crucial for efficiently incorporating its use into potential therapeutic strategies.

  8. Fabrication of conductive NGF-conjugated polypyrrole-poly(l-lactic acid) fibers and their effect on neurite outgrowth.

    PubMed

    Zeng, Jingwen; Huang, Zhongbing; Yin, Guangfu; Qin, Jiabang; Chen, Xianchun; Gu, Jianwen

    2013-10-01

    In order to fabricate a tissue scaffold with the neurotrophic and electrical activities, conductive nerve growth factor (NGF)-conjugated polypyrrole-poly(l-lactic acid) (PPy-PLLA) composite fibers were prepared by oxidation polymerization and EDC chemistry with poly-l-lysine. PPy nanoparticles (∼70nm diameter) accumulated on PLLA fiber surface to form a rough thick shell (∼200nm thickness). These NGF-conjugated PPy-PLLA fibers could support PC12 neurite outgrowth and extension. Especially, 40% and 74% increase in PC12 neurite outgrowth and extension, respectively, could be obtained under electrical stimulation of 100mV/cm voltages through the composite fibers. A mechanism for the interaction between neurite extension and the NGF-conjugated PPy-PLLA fibers under electro-stimulation was proposed, to explain the synergistic effect of the rough PPy shell, conjugated NGF and electricity on neurite outgrowth and elongation. PMID:23759386

  9. Wave Journal Bearings Under Dynamic Loads

    NASA Technical Reports Server (NTRS)

    Hendricks, Robert C.; Dimofte, Florin

    2002-01-01

    The dynamic behavior of the wave journal bearing was determined by running a three-wave bearing with an eccentrically mounted shaft. A transient analysis was developed and used to predict numerical data for the experimental cases. The three-wave journal bearing ran stably under dynamic loads with orbits well inside the bearing clearance. The orbits were almost circular and nearly free of the influence of, but dynamically dependent on, bearing wave shape. Experimental observations for both the absolute bearing-housing-center orbits and the relative bearing-housing-center-to-shaft-center orbits agreed well with the predictions. Moreover, the subsynchronous whirl motion generated by the fluid film was found experimentally and predicted theoretically for certain speeds.

  10. Noise facilitates transcriptional control under dynamic inputs.

    PubMed

    Kellogg, Ryan A; Tay, Savaş

    2015-01-29

    Cells must respond sensitively to time-varying inputs in complex signaling environments. To understand how signaling networks process dynamic inputs into gene expression outputs and the role of noise in cellular information processing, we studied the immune pathway NF-κB under periodic cytokine inputs using microfluidic single-cell measurements and stochastic modeling. We find that NF-κB dynamics in fibroblasts synchronize with oscillating TNF signal and become entrained, leading to significantly increased NF-κB oscillation amplitude and mRNA output compared to non-entrained response. Simulations show that intrinsic biochemical noise in individual cells improves NF-κB oscillation and entrainment, whereas cell-to-cell variability in NF-κB natural frequency creates population robustness, together enabling entrainment over a wider range of dynamic inputs. This wide range is confirmed by experiments where entrained cells were measured under all input periods. These results indicate that synergy between oscillation and noise allows cells to achieve efficient gene expression in dynamically changing signaling environments. PMID:25635454

  11. Nanostructured Polyaniline Coating on ITO Glass Promotes the Neurite Outgrowth of PC 12 Cells by Electrical Stimulation.

    PubMed

    Wang, Liping; Huang, Qianwei; Wang, Jin-Ye

    2015-11-10

    A conducting polymer polyaniline (PANI) with nanostructure was synthesized on indium tin oxide (ITO) glass. The effect of electrical stimulation on the proliferation and the length of neurites of PC 12 cells was investigated. The dynamic protein adsorption on PANI and ITO surfaces in a cell culture medium was also compared with and without electrical stimulation. The adsorbed proteins were characterized using SDS-PAGE. A PANI coating on ITO surface was shown with 30-50 nm spherical nanostructure. The number of PC 12 cells was significantly greater on the PANI/ITO surface than on ITO and plate surfaces after cell seeding for 24 and 36 h. This result confirmed that the PANI coating is nontoxic to PC 12 cells. The electrical stimulation for 1, 2, and 4 h significantly enhanced the cell numbers for both PANI and ITO conducting surfaces. Moreover, the application of electrical stimulation also improved the neurite outgrowth of PC 12 cells, and the number of PC 12 cells with longer neurite lengths increased obviously under electrical stimulation for the PANI surface. From the mechanism, the adsorption of DMEM proteins was found to be enhanced by electrical stimulation for both PANI/ITO and ITO surfaces. A new band 2 (around 37 kDa) was observed from the collected adsorbed proteins when PC 12 cells were cultured on these surfaces, and culturing PC 12 cells also seemed to increase the amount of band 1 (around 90 kDa). When immersing PANI/ITO and ITO surfaces in a DMEM medium without a cell culture, the number of band 3 (around 70 kDa) and band 4 (around 45 kDa) proteins decreased compared to that of PC 12 cell cultured surfaces. These results are valuable for the design and improvement of the material performance for neural regeneration. PMID:25992643

  12. Dynamic Strength Ceramic Nanocomposites Under Pulse Loading

    NASA Astrophysics Data System (ADS)

    Skripnyak, Evgeniya G.; Skripnyak, Vladimir V.; Vaganova, Irina K.; Skripnyak, Vladimir A.

    2015-06-01

    Multi-scale computer simulation approach has been applied to research of strength of nanocomposites under dynamic loading. The influence of mesoscopic substructures on the dynamic strength of ceramic and hybrid nanocomposites, which can be formed using additive manufacturing were numerically investigated. At weak shock wave loadings the shear strength and the spall strength of ceramic and hybrid nanocomposites depends not only phase concentration and porosity, but size parameters of skeleton substructures. The influence of skeleton parameter on the shear strength and the spall strength of ceramic nanocomposites with the same concentration of phases decreases with increasing amplitude of the shock pulse of microsecond duration above the double amplitude of the Hugoniot elastic limit of nanocomposites. This research carried out in 2014 -2015 was supported by grant from The Tomsk State University Academic D.I. Mendeleev Fund Program and also Ministry of Sciences and Education of Russian Federation (State task 2014/223, project 1943, Agreement 14.132.

  13. Hericium erinaceus (Bull.: Fr) Pers. cultivated under tropical conditions: isolation of hericenones and demonstration of NGF-mediated neurite outgrowth in PC12 cells via MEK/ERK and PI3K-Akt signaling pathways.

    PubMed

    Phan, Chia-Wei; Lee, Guan-Serm; Hong, Sok-Lai; Wong, Yuin-Teng; Brkljača, Robert; Urban, Sylvia; Abd Malek, Sri Nurestri; Sabaratnam, Vikineswary

    2014-12-01

    Hericium erinaceus (Bull.: Fr.) Pers. is an edible and medicinal mushroom used traditionally to improve memory. In this study, we investigated the neuritogenic effects of hericenones isolated from H. erinaceus and the mechanisms of action involved. H. erinaceus was cultivated and the secondary metabolites were elucidated by high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR). The secondary metabolites were tested for neurite outgrowth activity (if any). Rat pheochromocytoma (PC12) cells were employed and the nerve growth factor (NGF) level was also determined. The signaling pathways involved in the mushroom-induced neuritogenesis were investigated using several pharmacological inhibitors. Hericenones B-E (1-4), erinacerin A (5) and isohericerin (6) were isolated from the basidiocarps of H. erinaceus. The hericenones did not promote neurite outgrowth but when induced with a low concentration of NGF (5 ng mL(-1)), the neuritogenic activity was comparable to that of the positive control (50 ng mL(-1) of NGF). Hericenone E was able to stimulate NGF secretion which was two-fold higher than that of the positive control. The neuritogenesis process was partially blocked by the tyrosine kinase receptor (Trk) inhibitor, K252a, suggesting that the neuritogenic effect was not solely due to NGF. Hericenone E also increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Taken together, this study suggests that hericenone E potentiated NGF-induced neuritogenesis in PC12 cells via the MEK/ERK and PI3K/Akt pathways. PMID:25288148

  14. Dynamic Epistasis under Varying Environmental Perturbations

    PubMed Central

    Barker, Brandon; Xu, Lin; Gu, Zhenglong

    2015-01-01

    Epistasis describes the phenomenon that mutations at different loci do not have independent effects with regard to certain phenotypes. Understanding the global epistatic landscape is vital for many genetic and evolutionary theories. Current knowledge for epistatic dynamics under multiple conditions is limited by the technological difficulties in experimentally screening epistatic relations among genes. We explored this issue by applying flux balance analysis to simulate epistatic landscapes under various environmental perturbations. Specifically, we looked at gene-gene epistatic interactions, where the mutations were assumed to occur in different genes. We predicted that epistasis tends to become more positive from glucose-abundant to nutrient-limiting conditions, indicating that selection might be less effective in removing deleterious mutations in the latter. We also observed a stable core of epistatic interactions in all tested conditions, as well as many epistatic interactions unique to each condition. Interestingly, genes in the stable epistatic interaction network are directly linked to most other genes whereas genes with condition-specific epistasis form a scale-free network. Furthermore, genes with stable epistasis tend to have similar evolutionary rates, whereas this co-evolving relationship does not hold for genes with condition-specific epistasis. Our findings provide a novel genome-wide picture about epistatic dynamics under environmental perturbations. PMID:25625594

  15. Diazinon and diazoxon impair the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons

    SciTech Connect

    Pizzurro, Daniella M.; Dao, Khoi; Costa, Lucio G.

    2014-02-01

    Evidence from in vivo and epidemiological studies suggests that organophosphorus insecticides (OPs) are developmental neurotoxicants, but possible underlying mechanisms are still unclear. Astrocytes are increasingly recognized for their active role in normal neuronal development. This study sought to investigate whether the widely-used OP diazinon (DZ), and its oxygen metabolite diazoxon (DZO), would affect glial–neuronal interactions as a potential mechanism of developmental neurotoxicity. Specifically, we investigated the effects of DZ and DZO on the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons. The results show that both DZ and DZO adversely affect astrocyte function, resulting in inhibited neurite outgrowth in hippocampal neurons. This effect appears to be mediated by oxidative stress, as indicated by OP-induced increased reactive oxygen species production in astrocytes and prevention of neurite outgrowth inhibition by antioxidants. The concentrations of OPs were devoid of cytotoxicity, and cause limited acetylcholinesterase inhibition in astrocytes (18 and 25% for DZ and DZO, respectively). Among astrocytic neuritogenic factors, the most important one is the extracellular matrix protein fibronectin. DZ and DZO decreased levels of fibronectin in astrocytes, and this effect was also attenuated by antioxidants. Underscoring the importance of fibronectin in this context, adding exogenous fibronectin to the co-culture system successfully prevented inhibition of neurite outgrowth caused by DZ and DZO. These results indicate that DZ and DZO increase oxidative stress in astrocytes, and this in turn modulates astrocytic fibronectin, leading to impaired neurite outgrowth in hippocampal neurons. - Highlights: • DZ and DZO inhibit astrocyte-mediated neurite outgrowth in rat hippocampal neurons. • Oxidative stress is involved in inhibition of neuritogenesis by DZ and DZO. • DZ and DZO decrease expression of the neuritogenic

  16. An algorithm for neurite outgrowth reconstruction

    NASA Technical Reports Server (NTRS)

    Weaver, Christina M.; Pinezich, John D.; Lindquist, W. Brent; Vazquez, Marcelo E.

    2003-01-01

    We present a numerical method which provides the ability to analyze digitized microscope images of retinal explants and quantify neurite outgrowth. Few parameters are required as input and limited user interaction is necessary to process an entire experiment of images. This eliminates fatigue related errors and user-related bias common to manual analysis. The method does not rely on stained images and handles images of variable quality. The algorithm is used to determine time and dose dependent, in vitro, neurotoxic effects of 1 GeV per nucleon iron particles in retinal explants. No neurotoxic effects are detected until 72 h after exposure; at 72 h, significant reductions of neurite outgrowth occurred at doses higher than 10 cGy.

  17. Assessment of chemical-induced impairment of human neurite outgrowth by multiparametric live cell imaging in high-density cultures.

    PubMed

    Stiegler, Nina V; Krug, Anne K; Matt, Florian; Leist, Marcel

    2011-05-01

    Chemicals that specifically alter human neurite outgrowth pose a hazard for the development of the nervous system. The identification of such compounds remains a major challenge, especially in a human test system. To address this issue, we developed an imaging-based procedure in LUHMES human neuronal precursor cells to quantify neurite growth of unfixed cultures. Live imaging allowed the simultaneous evaluation of cell viability and neurite outgrowth within one culture dish. The procedure was used to test the hypothesis that inhibitors of specific pathways can impair neurite outgrowth without affecting cell viability. Although the cells were grown at high density to allow extensive networking, overall neurite growth in this complex culture was quantified with a signal-to-noise ratio of > 50. Compounds such as U0126 slowed the extension of neuronal processes at concentrations > 4 times lower than those causing cell death. High numbers of individual viable cells without neurites were identified under such conditions, and neurite outgrowth recovered after washout of the chemical. Also an extension-promoting compound, Y-27632, was identified by this unique multiparametric imaging approach. Finally, the actions of unspecific cytotoxicants such as menadione, cadmium chloride, and sodium dodecyl sulfate were tested to evaluate the specificity of the new assay. We always found a ratio of EC50 (cell death)/EC50 (neurites) < 4 for such chemicals. The described novel test system may thus be useful both for high-throughput screens to identify neuritotoxic agents and for their closer characterization concerning mode of action, compound interactions, or the reversibility of their effects. PMID:21342877

  18. Optimizing neurotrophic factor combinations for neurite outgrowth

    NASA Astrophysics Data System (ADS)

    Deister, C.; Schmidt, C. E.

    2006-06-01

    Most neurotrophic factors are members of one of three families: the neurotrophins, the glial cell-line derived neurotrophic factor family ligands (GFLs) and the neuropoietic cytokines. Each family activates distinct but overlapping cellular pathways. Several studies have shown additive or synergistic interactions between neurotrophic factors from different families, though generally only a single combination has been studied. Because of possible interactions between the neurotrophic factors, the optimum concentration of a factor in a mixture may differ from the optimum when applied individually. Additionally, the effect of combinations of neurotrophic factors from each of the three families on neurite extension is unclear. This study examines the effects of several combinations of the neurotrophin nerve growth factor (NGF), the GFL glial cell-line derived neurotrophic factor (GDNF) and the neuropoietic cytokine ciliary neurotrophic factor (CNTF) on neurite outgrowth from young rat dorsal root ganglion (DRG) explants. The combination of 50 ng ml-1 NGF and 10 ng ml-1 of each GDNF and CNTF induced the highest level of neurite outgrowth at a 752 ± 53% increase over untreated DRGs and increased the longest neurite length to 2031 ± 97 µm compared to 916 ± 64 µm for untreated DRGs. The optimum concentrations of the three factors applied in combination corresponded to the optimum concentration of each factor when applied individually. These results indicate that the efficacy of future therapies for nerve repair would be enhanced by the controlled release of a combination of neurotrophins, GFLs and neuropoietic cytokines at higher concentrations than used in previous conduit designs.

  19. Spatial Phosphoprotein Profiling Reveals a Compartmentalized Extracellular Signal-regulated Kinase Switch Governing Neurite Growth and Retraction

    SciTech Connect

    Wang, Yingchun; Yang, Feng; Fu, Yi; Huang, Xiahe; Wang, Wei; Jiang, Xining; Gritsenko, Marina A.; Zhao, Rui; Monroe, Matthew E.; Pertz, Olivier C.; Purvine, Samuel O.; Orton, Daniel J.; Jacobs, Jon M.; Camp, David G.; Smith, Richard D.; Klemke, Richard L.

    2011-05-20

    Abstract - Brain development and spinal cord regeneration require neurite sprouting and growth cone navigation in response to extension and collapsing factors present in the extracellular environment. These external guidance cues control neurite growth cone extension and retraction processes through intracellular protein phosphorylation of numerous cytoskeletal, adhesion, and polarity complex signaling proteins. However, the complex kinase/substrate signaling networks that mediate neuritogenesis have not been investigated. Here, we compare the neurite phosphoproteome under growth and retraction conditions using neurite purification methodology combined with mass spectrometry. More than 4000 non-redundant phosphorylation sites from 1883 proteins have been annotated and mapped to signaling pathways that control kinase/phosphatase networks, cytoskeleton remodeling, and axon/dendrite specification. Comprehensive informatics and functional studies revealed a compartmentalized ERK activation/deactivation cytoskeletal switch that governs neurite growth and retraction, respectively. Our findings provide the first system-wide analysis of the phosphoprotein signaling networks that enable neurite growth and retraction and reveal an important molecular switch that governs neuritogenesis.

  20. Dynamic Strength of Tantalum under impact

    NASA Astrophysics Data System (ADS)

    Glam, Benny; Werdiger, Meir; Pistinner, Shlomi

    2013-06-01

    Plane impact experiments of double shock and shock-rarefaction in Tantalum were carried out in a gas gun. VISAR diagnostics has been implemented to measure the particle velocity and the free surface velocity. The VISAR information was utilized to study the dynamic strength of Tantalum under compression and tension. The pressure in the experiments was below 35 GPa. In this pressure range the dominant mechanism is expected to be dislocation motion. A 1-d hydrodynamic code was used in order to match various strength models. As expected, both the Johnson-Cook and the Guinan-Steinberg models do not reproduce the experimental results. Therefore in this paper we compare the Zerilli-Armstrong model which has been recently calibrated at strain rate of 6 x 103 s-1 using the split Kowalsky-Hopkinson bar to our experimental results at strain rate of 106 s-1.

  1. Eigenvector dynamics under perturbation of modular networks

    NASA Astrophysics Data System (ADS)

    Sarkar, Somwrita; Chawla, Sanjay; Robinson, P. A.; Fortunato, Santo

    2016-06-01

    Rotation dynamics of eigenvectors of modular network adjacency matrices under random perturbations are presented. In the presence of q communities, the number of eigenvectors corresponding to the q largest eigenvalues form a "community" eigenspace and rotate together, but separately from that of the "bulk" eigenspace spanned by all the other eigenvectors. Using this property, the number of modules or clusters in a network can be estimated in an algorithm-independent way. A general argument and derivation for the theoretical detectability limit for sparse modular networks with q communities is presented, beyond which modularity persists in the system but cannot be detected. It is shown that for detecting the clusters or modules using the adjacency matrix, there is a "band" in which it is hard to detect the clusters even before the theoretical detectability limit is reached, and for which the theoretically predicted detectability limit forms the sufficient upper bound. Analytic estimations of these bounds are presented and empirically demonstrated.

  2. Reliability of dynamic systems under limited information.

    SciTech Connect

    Field, Richard V., Jr.; Grigoriu, Mircea

    2006-09-01

    A method is developed for reliability analysis of dynamic systems under limited information. The available information includes one or more samples of the system output; any known information on features of the output can be used if available. The method is based on the theory of non-Gaussian translation processes and is shown to be particularly suitable for problems of practical interest. For illustration, we apply the proposed method to a series of simple example problems and compare with results given by traditional statistical estimators in order to establish the accuracy of the method. It is demonstrated that the method delivers accurate results for the case of linear and nonlinear dynamic systems, and can be applied to analyze experimental data and/or mathematical model outputs. Two complex applications of direct interest to Sandia are also considered. First, we apply the proposed method to assess design reliability of a MEMS inertial switch. Second, we consider re-entry body (RB) component vibration response during normal re-entry, where the objective is to estimate the time-dependent probability of component failure. This last application is directly relevant to re-entry random vibration analysis at Sandia, and may provide insights on test-based and/or model-based qualification of weapon components for random vibration environments.

  3. Facile micropatterning of dual hydrogel systems for 3D models of neurite outgrowth.

    PubMed

    Curley, J Lowry; Moore, Michael J

    2011-12-15

    Understanding how microenvironmental factors influence neurite growth is important to inform studies in nerve regeneration, plasticity, development, and neurophysiology. In vitro models attempting to more accurately mimic the physiological environment by provision of a 3D growth matrix may provide useful foundations. Some limitations of thick 3D culture models include hampered solute transport, less-robust neurite growth than on 2D substrates, and difficulty in achieving spatial control of growth. To this end, we describe a 3D dual hydrogel model for embryonic rat day 15 dorsal root ganglion tissue explant growth using a digital micromirror device for dynamic mask projection photolithography. The photolithography method developed allowed simple, reproducible, one-step fabrication of thick hydrogel constructs on a variety of substrates, including permeable cell culture inserts. The relationships between projected mask size, crosslinked hydrogel resolution, and gel thickness were characterized, and resolution was found generally to decrease with increasing gel thickness. Cell viability in thick (481 μm) hydrogel constructs was significantly greater on permeable supports than glass, suggesting transport limitations were somewhat alleviated. The observed neurite growth was abundant and occurred in a spatially controlled manner throughout the 3D environment, a crucial step in the quest for a more effective biomimetic model of neurite outgrowth. PMID:21936043

  4. Facile micropatterning of dual hydrogel systems for 3D models of neurite outgrowth

    PubMed Central

    Curley, J L; Moore, M J

    2011-01-01

    Understanding how microenvironmental factors influence neurite growth is important to inform studies in nerve regeneration, plasticity, development, and neurophysiology. In vitro models attempting to more accurately mimic the physiological environment by provision of a 3D growth matrix may provide useful foundations. Some limitations of thick 3D culture models include hampered solute transport, less-robust neurite growth than on 2D substrates, and difficulty in achieving spatial control of growth. To this end, we describe a 3D dual hydrogel model for embryonic rat day 15 dorsal root ganglion tissue explant growth using a digital micro-mirror device for dynamic mask projection photolithography. The photolithography method developed allowed simple, reproducible, one-step fabrication of thick hydrogel constructs on a variety of substrates, including permeable cell culture inserts. The relationships between projected mask size, crosslinked hydrogel resolution, and gel thickness were characterized, and resolution was found generally to decrease with increasing gel thickness. Cell viability in thick (481 μm) hydrogel constructs was significantly greater on permeable supports than glass, suggesting transport limitations were somewhat alleviated. The observed neurite growth was abundant and occurred in a spatially controlled manner throughout the 3D environment, a crucial step in the quest for a more effective biomimetic model of neurite outgrowth. PMID:21936043

  5. Stochastic Dynamics Underlying Cognitive Stability and Flexibility

    PubMed Central

    Ueltzhöffer, Kai; Armbruster-Genç, Diana J. N.; Fiebach, Christian J.

    2015-01-01

    dopaminergic modulation of cognitive flexibility. These results show that stochastic dynamical systems can implement the basic computations underlying cognitive stability and flexibility and explain neurobiological bases of individual differences. PMID:26068119

  6. Stochastic Dynamics Underlying Cognitive Stability and Flexibility.

    PubMed

    Ueltzhöffer, Kai; Armbruster-Genç, Diana J N; Fiebach, Christian J

    2015-06-01

    dopaminergic modulation of cognitive flexibility. These results show that stochastic dynamical systems can implement the basic computations underlying cognitive stability and flexibility and explain neurobiological bases of individual differences. PMID:26068119

  7. Fabrication of Aligned Conducting PPy-PLLA Fiber Films and Their Electrically Controlled Guidance and Orientation for Neurites.

    PubMed

    Zou, Yuanwen; Qin, Jiabang; Huang, Zhongbing; Yin, Guangfu; Pu, Ximing; He, Da

    2016-05-25

    Electrically conductive biomaterial scaffolds have great potential in neural tissue regeneration. In this work, an aligned conductive fibrous scaffold was prepared by electrospinning PLLA on rotating collector and chemical oxidation polymerization of pyrrole (PPy) codoped with poly(glutamic acid)/dodecyl benzenesulfonic acid sodium. The characterization results of composition, structure and mechanics of fiber films show that the existence of weak polar van der Waals' force between PPy coating and PLLA fibers. The resistivity of aligned rough PPy-PLLA fiber film (about 800 nm of fiber diameter) at the perpendicular and parallel directions is 0.971 and 0.874 Ω m, respectively. Aligned rough PPy-PLLA fiber film could guide the extension of 68% PC12 neurites along the direction of fiber axis. Under electrostimulation (ES) of 100, 200, and 400 mV/cm, median neurite lengths of differentiated PC12 on aligned fiber-films are 128, 149, and 141 μm, respectively. Furthermore, under ES of 100, 200, and 400 mV/cm, the alignment rate of neurite along the electropotential direction (angle between neurite and electropotential direction ≤10°) on random fibers film are 17, 23, and 28%, respectively, and the alignment rate of neurites along the fiber axis (angle between neurite and fiber axis ≤10°) on aligned fibers film reach to 76, 83, and 79%, respectively, indicating that the combination of ES and rough conducting aligned structure could adjust the alignment of cellular neurites along the direction of the fiber axis or electropotential. PMID:27172537

  8. Controlled neuronal cell patterning and guided neurite growth on micropatterned nanofiber platforms

    NASA Astrophysics Data System (ADS)

    Malkoc, Veysi; Gallego-Perez, Daniel; Nelson, Tyler; Lannutti, John J.; Hansford, Derek J.

    2015-12-01

    Patterning neuronal cells and guiding neurite growth are important for applications such as prosthetics, cell based biosensors, and tissue engineering. In this paper, a microdevice is presented that provides neuronal cell patterning and guided neurite growth on a collagen coated gelatin/PCL nanofiber mat. The pattern consisted of a grid of polystyrene microwells/nodes to confine the cell bodies and orthogonal grooves to guide neurite growth from each node. Vacuum assisted cell seeding was used to localize cell bodies in the microwells and physically separate the cells during seeding. The electrospun nanofiber mats under the polystyrene microstructures were coated with collagen to enhance the cellular attachment and enhance differentiation. We evaluated the performance of our device using adhesion, viability, and differentiation assays of neuron-like PC12 cells compared to controls for vacuum seeding, spatial isolation and guidance, and collagen coating of the fibers. The device provided PC12 cell patterning with increased adhesion, differentiation, and guided neurite outgrowth compared to controls, demonstrating its potential for in vitro neuronal cell patterning studies.

  9. The combinatorics of neurite self-avoidance.

    PubMed

    Forbes, Elizabeth M; Hunt, Jonathan J; Goodhill, Geoffrey J

    2011-11-01

    During neural development in Drosophila, the ability of neurite branches to recognize whether they are from the same or different neurons depends crucially on the molecule Dscam1. In particular, this recognition depends on the stochastic acquisition of a unique combination of Dscam1 isoforms out of a large set of possible isoforms. To properly interpret these findings, it is crucial to understand the combinatorics involved, which has previously been attempted only using stochastic simulations for some specific parameter combinations. Here we present closed-form solutions for the general case. These reveal the relationships among the key variables and how these constrain possible biological scenarios. PMID:21732864

  10. Stochastic game dynamics under demographic fluctuations

    PubMed Central

    Huang, Weini; Hauert, Christoph; Traulsen, Arne

    2015-01-01

    Frequency-dependent selection and demographic fluctuations play important roles in evolutionary and ecological processes. Under frequency-dependent selection, the average fitness of the population may increase or decrease based on interactions between individuals within the population. This should be reflected in fluctuations of the population size even in constant environments. Here, we propose a stochastic model that naturally combines these two evolutionary ingredients by assuming frequency-dependent competition between different types in an individual-based model. In contrast to previous game theoretic models, the carrying capacity of the population, and thus the population size, is determined by pairwise competition of individuals mediated by evolutionary games and demographic stochasticity. In the limit of infinite population size, the averaged stochastic dynamics is captured by deterministic competitive Lotka–Volterra equations. In small populations, demographic stochasticity may instead lead to the extinction of the entire population. Because the population size is driven by fitness in evolutionary games, a population of cooperators is less prone to go extinct than a population of defectors, whereas in the usual systems of fixed size the population would thrive regardless of its average payoff. PMID:26150518

  11. Stochastic game dynamics under demographic fluctuations.

    PubMed

    Huang, Weini; Hauert, Christoph; Traulsen, Arne

    2015-07-21

    Frequency-dependent selection and demographic fluctuations play important roles in evolutionary and ecological processes. Under frequency-dependent selection, the average fitness of the population may increase or decrease based on interactions between individuals within the population. This should be reflected in fluctuations of the population size even in constant environments. Here, we propose a stochastic model that naturally combines these two evolutionary ingredients by assuming frequency-dependent competition between different types in an individual-based model. In contrast to previous game theoretic models, the carrying capacity of the population, and thus the population size, is determined by pairwise competition of individuals mediated by evolutionary games and demographic stochasticity. In the limit of infinite population size, the averaged stochastic dynamics is captured by deterministic competitive Lotka-Volterra equations. In small populations, demographic stochasticity may instead lead to the extinction of the entire population. Because the population size is driven by fitness in evolutionary games, a population of cooperators is less prone to go extinct than a population of defectors, whereas in the usual systems of fixed size the population would thrive regardless of its average payoff. PMID:26150518

  12. Insulin signaling regulates neurite growth during metamorphic neuronal remodeling

    PubMed Central

    Gu, Tingting; Zhao, Tao; Hewes, Randall S.

    2014-01-01

    Summary Although the growth capacity of mature neurons is often limited, some neurons can shift through largely unknown mechanisms from stable maintenance growth to dynamic, organizational growth (e.g. to repair injury, or during development transitions). During insect metamorphosis, many terminally differentiated larval neurons undergo extensive remodeling, involving elimination of larval neurites and outgrowth and elaboration of adult-specific projections. Here, we show in the fruit fly, Drosophila melanogaster (Meigen), that a metamorphosis-specific increase in insulin signaling promotes neuronal growth and axon branching after prolonged stability during the larval stages. FOXO, a negative effector in the insulin signaling pathway, blocked metamorphic growth of peptidergic neurons that secrete the neuropeptides CCAP and bursicon. RNA interference and CCAP/bursicon cell-targeted expression of dominant-negative constructs for other components of the insulin signaling pathway (InR, Pi3K92E, Akt1, S6K) also partially suppressed the growth of the CCAP/bursicon neuron somata and neurite arbor. In contrast, expression of wild-type or constitutively active forms of InR, Pi3K92E, Akt1, Rheb, and TOR, as well as RNA interference for negative regulators of insulin signaling (PTEN, FOXO), stimulated overgrowth. Interestingly, InR displayed little effect on larval CCAP/bursicon neuron growth, in contrast to its strong effects during metamorphosis. Manipulations of insulin signaling in many other peptidergic neurons revealed generalized growth stimulation during metamorphosis, but not during larval development. These findings reveal a fundamental shift in growth control mechanisms when mature, differentiated neurons enter a new phase of organizational growth. Moreover, they highlight strong evolutionarily conservation of insulin signaling in neuronal growth regulation. PMID:24357229

  13. Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein.

    PubMed Central

    Cras, P; Kawai, M; Lowery, D; Gonzalez-DeWhitt, P; Greenberg, B; Perry, G

    1991-01-01

    Senile plaques are polymorphous beta-amyloid protein deposits found in the brain in Alzheimer disease and normal aging. This beta-amyloid protein is derived from a larger precursor molecule of which neurons are the principal producers in brain. We found that amyloid precursor protein (APP)-immunoreactive neurites were involved in senile plaques and that only a subset of these neurites showed markers for the abnormal filaments characteristic of neurofibrillary pathology. In the neocortex of nondemented individuals with senile plaques but spared of neurofibrillary pathology, dystrophic neurites in senile plaques showed only APP accumulation. In contrast, in the brains of Alzheimer patients, virtually all APP-immunoreactive neurites also showed immunoreactivity with ubiquitin, tau, and phosphorylated neurofilaments. The presence of tau and neurofilament epitopes in dystrophic neurites in senile plaques was correlated with the extent of neurofibrillary pathology in the surrounding brain tissue. Accumulation of APP and the formation of neurofibrillary pathology in senile plaque neurites are therefore distinct phenomena. Our findings suggest that APP accumulation in senile plaque neurites occurs prior to tau accumulation and is therefore more closely related to appearance of neuritic dystrophy. Images PMID:1652752

  14. Experimental and computational models of neurite extension at a choice point in response to controlled diffusive gradients

    NASA Astrophysics Data System (ADS)

    Catig, G. C.; Figueroa, S.; Moore, M. J.

    2015-08-01

    Ojective. Axons are guided toward desired targets through a series of choice points that they navigate by sensing cues in the cellular environment. A better understanding of how microenvironmental factors influence neurite growth during development can inform strategies to address nerve injury. Therefore, there is a need for biomimetic models to systematically investigate the influence of guidance cues at such choice points. Approach. We ran an adapted in silico biased turning axon growth model under the influence of nerve growth factor (NGF) and compared the results to corresponding in vitro experiments. We examined if growth simulations were predictive of neurite population behavior at a choice point. We used a biphasic micropatterned hydrogel system consisting of an outer cell restrictive mold that enclosed a bifurcated cell permissive region and placed a well near a bifurcating end to allow proteins to diffuse and form a gradient. Experimental diffusion profiles in these constructs were used to validate a diffusion computational model that utilized experimentally measured diffusion coefficients in hydrogels. The computational diffusion model was then used to establish defined soluble gradients within the permissive region of the hydrogels and maintain the profiles in physiological ranges for an extended period of time. Computational diffusion profiles informed the neurite growth model, which was compared with neurite growth experiments in the bifurcating hydrogel constructs. Main results. Results indicated that when applied to the constrained choice point geometry, the biased turning model predicted experimental behavior closely. Results for both simulated and in vitro neurite growth studies showed a significant chemoattractive response toward the bifurcated end containing an NGF gradient compared to the control, though some neurites were found in the end with no NGF gradient. Significance. The integrated model of neurite growth we describe will allow

  15. Biophysical mechanisms underlying olfactory receptor neuron dynamics

    PubMed Central

    Nagel, Katherine I.; Wilson, Rachel I.

    2010-01-01

    Odor responses of olfactory receptor neurons (ORNs) exhibit complex dynamics. Using genetics and pharmacology, we show that these dynamics in Drosophila ORNs can be separated into sequential steps, corresponding to transduction and spike generation. Each of these steps contributes distinct dynamics. Transduction dynamics can be largely explained by a simple kinetic model of ligand-receptor interactions, together with an adaptive feedback mechanism that slows transduction onset. Spiking dynamics are well-described by a differentiating linear filter that is stereotyped across odors and cells. Genetic knock-down of sodium channels reshapes this filter, implying that it arises from the regulated balance of intrinsic conductances in ORNs. Complex responses can be understood as a consequence of how the stereotyped spike filter interacts with odor- and receptor-specific transduction dynamics. However, in the presence of rapidly fluctuating natural stimuli, spiking simply increases the speed and sensitivity of encoding. PMID:21217763

  16. Real-time detection of neurite outgrowth using microfluidic device

    NASA Astrophysics Data System (ADS)

    Kim, Samhwan; Jang, Jongmoon; Choi, Hongsoo; Moon, Cheil

    2013-05-01

    We developed a simple method for real-time detection of the neurite outgrowth using microfluidic device. Our microfluidic device contains three compartmentalized channels which are for cell seeding, hydrogel and growth factors. Collagen gel is filled in the middle channel and pheochromocytoma (PC12) cells are seeded in the left channel. To induce differentiation of PC12 cells, 50 ng/ml to1000 ng/ml of nerve growth factor (NGF) is introduced into the right channel. After three days of NGF treatment, PC12 cells begin to extend neurites and formed neurite network from sixth day. Quantification of neurite outgrowth is analyzed by measuring the total area of neurites. On sixth day, the area is doubled compared to the area on third day and increases by 20 times on ninth day.

  17. Graphene substrate for inducing neurite outgrowth.

    PubMed

    Lee, Jeong Soon; Lipatov, Alexey; Ha, Ligyeom; Shekhirev, Mikhail; Andalib, Mohammad Nahid; Sinitskii, Alexander; Lim, Jung Yul

    2015-05-01

    A few recent studies demonstrated that graphene may have cytocompatibility with several cell types. However, when assessing cell behavior on graphene, there has been no precise control over the quality of graphene, number of graphene layers, and substrate surface coverage by graphene. In this study, using well-controlled monolayer graphene film substrates we tested the cytocompatibility of graphene for human neuroblastoma (SH-SY5Y) cell culture. A large-scale monolayer graphene film grown on Cu foils by chemical vapor deposition (CVD) could be successfully transferred onto glass substrates by wet transfer technique. We observed that graphene substrate could induce enhanced neurite outgrowth, both in neurite length and number, compared with control glass substrate. Interestingly, the positive stimulatory effect by graphene was achieved even in the absence of soluble neurogenic factor, retinoic acid (RA). Key genes relevant to cell neurogenesis, e.g., neurofilament light chain (NFL), were also upregulated on graphene. Inhibitor studies suggested that the graphene stimulation of cellular neurogenesis may be achieved through focal adhesion kinase (FAK) and p38 mitogen-activated protein kinase (MAPK) cascades. Our data indicate that graphene may be exploited as a platform for neural regenerative medicine, and the suggested molecular mechanism may provide an insight into the graphene control of neural cells. PMID:25778866

  18. An assay to image neuronal microtubule dynamics in mice

    PubMed Central

    Kleele, Tatjana; Marinković, Petar; Williams, Philip R.; Stern, Sina; Weigand, Emily E.; Engerer, Peter; Naumann, Ronald; Hartmann, Jana; Karl, Rosa M.; Bradke, Frank; Bishop, Derron; Herms, Jochen; Konnerth, Arthur; Kerschensteiner, Martin; Godinho, Leanne; Misgeld, Thomas

    2014-01-01

    Microtubule dynamics in neurons play critical roles in physiology, injury and disease and determine microtubule orientation, the cell biological correlate of neurite polarization. Several microtubule binding proteins, including end-binding protein 3 (EB3), specifically bind to the growing plus tip of microtubules. In the past, fluorescently tagged end-binding proteins have revealed microtubule dynamics in vitro and in non-mammalian model organisms. Here, we devise an imaging assay based on transgenic mice expressing yellow fluorescent protein-tagged EB3 to study microtubules in intact mammalian neurites. Our approach allows measurement of microtubule dynamics in vivo and ex vivo in peripheral nervous system and central nervous system neurites under physiological conditions and after exposure to microtubule-modifying drugs. We find an increase in dynamic microtubules after injury and in neurodegenerative disease states, before axons show morphological indications of degeneration or regrowth. Thus increased microtubule dynamics might serve as a general indicator of neurite remodelling in health and disease. PMID:25219969

  19. Increase in Growth Cone Size Correlates with Decrease in Neurite Growth Rate

    PubMed Central

    Ren, Yuan

    2016-01-01

    Several important discoveries in growth cone cell biology were made possible by the use of growth cones derived from cultured Aplysia bag cell neurons, including the characterization of the organization and dynamics of the cytoskeleton. The majority of these Aplysia studies focused on large growth cones induced by poly-L-lysine substrates at early stages in cell culture. Under these conditions, the growth cones are in a steady state with very little net advancement. Here, we offer a comprehensive cellular analysis of the motile behavior of Aplysia growth cones in culture beyond this pausing state. We found that average growth cone size decreased with cell culture time whereas average growth rate increased. This inverse correlation of growth rate and growth cone size was due to the occurrence of large growth cones with a peripheral domain larger than 100 μm2. The large pausing growth cones had central domains that were less consistently aligned with the direction of growth and could be converted into smaller, faster-growing growth cones by addition of a three-dimensional collagen gel. We conclude that the significant lateral expansion of lamellipodia and filopodia as observed during these culture conditions has a negative effect on neurite growth. PMID:27274874

  20. Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum

    PubMed Central

    Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R.; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

    2015-01-01

    Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain. PMID:25871402

  1. Matrix interactions modulate neurotrophin-mediated neurite outgrowth and pathfinding

    PubMed Central

    Madl, Christopher M.; Heilshorn, Sarah C.

    2015-01-01

    Both matrix biochemistry and neurotrophic factors are known to modulate neurite outgrowth and pathfinding; however, the interplay between these two factors is less studied. While previous work has shown that the biochemical identity of the matrix can alter the outgrowth of neurites in response to neurotrophins, the importance of the concentration of cell-adhesive ligands is unknown. Using engineered elastin-like protein matrices, we recently demonstrated a synergistic effect between matrix-bound cell-adhesive ligand density and soluble nerve growth factor treatment on neurite outgrowth from dorsal root ganglia. This synergism was mediated by Schwann cell-neurite contact through L1CAM. Cell-adhesive ligand density was also shown to alter the pathfinding behavior of dorsal root ganglion neurites in response to a gradient of nerve growth factor. While more cell-adhesive matrices promoted neurite outgrowth, less cell-adhesive matrices promoted more faithful neurite pathfinding. These studies emphasize the importance of considering both matrix biochemistry and neurotrophic factors when designing biomaterials for peripheral nerve regeneration. PMID:26170800

  2. Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum.

    PubMed

    Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

    2015-05-10

    Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain. PMID:25871402

  3. Dynamics of social balance under temporal interaction

    NASA Astrophysics Data System (ADS)

    Nishi, Ryosuke; Masuda, Naoki

    2014-08-01

    Real social contacts are often intermittent such that a link between a pair of nodes in a social network is only temporarily used. The effects of such temporal networks on social dynamics have been investigated for several phenomenological models such as epidemic spreading, linear diffusion processes, and nonlinear oscillations. Here, we numerically investigate nonlinear social balance dynamics in such a situation. Social balance is a classical psychological theory, which dictates that a triad is balanced if the three agents are mutual friends or if the two of them are the friends of each other and hostile to the other agent. We show that the social balance dynamics is slowed down on the temporal complete graph as compared to the corresponding static complete graph.

  4. Mechanical stress activates neurites and somata of myenteric neurons

    PubMed Central

    Kugler, Eva M.; Michel, Klaus; Zeller, Florian; Demir, Ihsan E.; Ceyhan, Güralp O.; Schemann, Michael; Mazzuoli-Weber, Gemma

    2015-01-01

    The particular location of myenteric neurons, sandwiched between the 2 muscle layers of the gut, implies that their somata and neurites undergo mechanical stress during gastrointestinal motility. Existence of mechanosensitive enteric neurons (MEN) is undoubted but many of their basic features remain to be studied. In this study, we used ultra-fast neuroimaging to record activity of primary cultured myenteric neurons of guinea pig and human intestine after von Frey hair evoked deformation of neurites and somata. Independent component analysis was applied to reconstruct neuronal morphology and follow neuronal signals. Of the cultured neurons 45% (114 out of 256, 30 guinea pigs) responded to neurite probing with a burst spike frequency of 13.4 Hz. Action potentials generated at the stimulation site invaded the soma and other neurites. Mechanosensitive sites were expressed across large areas of neurites. Many mechanosensitive neurites appeared to have afferent and efferent functions as those that responded to deformation also conducted spikes coming from the soma. Mechanosensitive neurites were also activated by nicotine application. This supported the concept of multifunctional MEN. 14% of the neurons (13 out of 96, 18 guinea pigs) responded to soma deformation with burst spike discharge of 17.9 Hz. Firing of MEN adapted rapidly (RAMEN), slowly (SAMEN), or ultra-slowly (USAMEN). The majority of MEN showed SAMEN behavior although significantly more RAMEN occurred after neurite probing. Cultured myenteric neurons from human intestine had similar properties. Compared to MEN, dorsal root ganglion neurons were activated by neurite but not by soma deformation with slow adaptation of firing. We demonstrated that MEN exhibit specific features very likely reflecting adaptation to their specialized functions in the gut. PMID:26441520

  5. Mechanical stress activates neurites and somata of myenteric neurons.

    PubMed

    Kugler, Eva M; Michel, Klaus; Zeller, Florian; Demir, Ihsan E; Ceyhan, Güralp O; Schemann, Michael; Mazzuoli-Weber, Gemma

    2015-01-01

    The particular location of myenteric neurons, sandwiched between the 2 muscle layers of the gut, implies that their somata and neurites undergo mechanical stress during gastrointestinal motility. Existence of mechanosensitive enteric neurons (MEN) is undoubted but many of their basic features remain to be studied. In this study, we used ultra-fast neuroimaging to record activity of primary cultured myenteric neurons of guinea pig and human intestine after von Frey hair evoked deformation of neurites and somata. Independent component analysis was applied to reconstruct neuronal morphology and follow neuronal signals. Of the cultured neurons 45% (114 out of 256, 30 guinea pigs) responded to neurite probing with a burst spike frequency of 13.4 Hz. Action potentials generated at the stimulation site invaded the soma and other neurites. Mechanosensitive sites were expressed across large areas of neurites. Many mechanosensitive neurites appeared to have afferent and efferent functions as those that responded to deformation also conducted spikes coming from the soma. Mechanosensitive neurites were also activated by nicotine application. This supported the concept of multifunctional MEN. 14% of the neurons (13 out of 96, 18 guinea pigs) responded to soma deformation with burst spike discharge of 17.9 Hz. Firing of MEN adapted rapidly (RAMEN), slowly (SAMEN), or ultra-slowly (USAMEN). The majority of MEN showed SAMEN behavior although significantly more RAMEN occurred after neurite probing. Cultured myenteric neurons from human intestine had similar properties. Compared to MEN, dorsal root ganglion neurons were activated by neurite but not by soma deformation with slow adaptation of firing. We demonstrated that MEN exhibit specific features very likely reflecting adaptation to their specialized functions in the gut. PMID:26441520

  6. Nerve abscess in primary neuritic leprosy.

    PubMed

    Rai, Dheeraj; Malhotra, Hardeep Singh; Garg, Ravindra Kumar; Goel, Madhu Mati; Malhotra, Kiran Preet; Kumar, Vijay; Singh, Arun Kumar; Jain, Amita; Kohli, Neera; Singh, Shailesh Kumar

    2013-06-01

    Nerve abscess is an infrequently reported complication of leprosy. We describe a patient with a pure neuritic type of leprosy with multiple nerve abscesses, who presented with tingling and numbness in the medial aspect of his right forearm and hand. Subsequently he developed pain, redness and swelling over the medial side of his right elbow and the flexor aspect of his right wrist. High-resolution ultrasound showed diffuse thickening of the right ulnar nerve with hypoechoic texture housing a cystic lesion with internal debris suggesting an abscess, at the cubital tunnel. Histopathological examination of the pus and tissue obtained from the abscess revealed presence of granulomas with lepra bacilli. The patient responded to surgery and multidrug therapy. In conclusion, the nerve abscess as the first manifestation of leprosy is uncommon and a high index of suspicion is required to make a correct diagnosis. PMID:24171239

  7. Evolution of entanglement under echo dynamics

    SciTech Connect

    Prosen, Tomaz; Znidaric, Marko; Seligman, Thomas H.

    2003-04-01

    Echo dynamics and fidelity are often used to discuss stability in quantum-information processing and quantum chaos. Yet fidelity yields no information about entanglement, the characteristic property of quantum mechanics. We study the evolution of entanglement in echo dynamics. We find qualitatively different behavior between integrable and chaotic systems on one hand and between random and coherent initial states for integrable systems on the other. For the latter the evolution of entanglement is given by a classical time scale. Analytic results are illustrated numerically in a Jaynes-Cummings model.

  8. Purines in neurite growth and astroglia activation.

    PubMed

    Heine, Claudia; Sygnecka, Katja; Franke, Heike

    2016-05-01

    The mammalian nervous system is a complex, functional network of neurons, consisting of local and long-range connections. Neuronal growth is highly coordinated by a variety of extracellular and intracellular signaling molecules. Purines turned out to be an essential component of these processes. Here, we review the current knowledge about the involvement of purinergic signaling in the regulation of neuronal development. We particularly focus on its role in neuritogenesis: the formation and extension of neurites. In the course of maturation mammals generally lose their ability to regenerate the central nervous system (CNS) e.g. after traumatic brain injury; although, spontaneous regeneration still occurs in the peripheral nervous system (PNS). Thus, it is crucial to translate the knowledge about CNS development and PNS regeneration into novel approaches to enable neurons of the mature CNS to regenerate. In this context we give a general overview of growth-inhibitory and growth-stimulatory factors and mechanisms involved in neurite growth. With regard to neuronal growth, astrocytes are an important cell population. They provide structural and metabolic support to neurons and actively participate in brain signaling. Astrocytes respond to injury with beneficial or detrimental reactions with regard to axonal growth. In this review we present the current knowledge of purines in these glial functions. Moreover, we discuss organotypic brain slice co-cultures as a model which retains neuron-glia interactions, and further presents at once a model for CNS development and regeneration. In summary, the purinergic system is a pivotal factor in neuronal development and in the response to injury. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID:26498067

  9. Dynamics Explorer twin spacecraft under evaluation tests

    NASA Technical Reports Server (NTRS)

    Redmond, C.

    1981-01-01

    The Dynamics Explorer A and B satellites designed to explore the interactive processes occuring between the magnetosphere and Earth's ionosphere, upper atmosphere, and plasmasphere are described. Effects of these interactions, satellite orbits, data collecting antennas, solar power systems, axes, configurations, and Earth based command, control and data display systems are mentioned.

  10. Leucine-rich repeat kinase 2 interacts with p21-activated kinase 6 to control neurite complexity in mammalian brain.

    PubMed

    Civiero, Laura; Cirnaru, Maria Daniela; Beilina, Alexandra; Rodella, Umberto; Russo, Isabella; Belluzzi, Elisa; Lobbestael, Evy; Reyniers, Lauran; Hondhamuni, Geshanthi; Lewis, Patrick A; Van den Haute, Chris; Baekelandt, Veerle; Bandopadhyay, Rina; Bubacco, Luigi; Piccoli, Giovanni; Cookson, Mark R; Taymans, Jean-Marc; Greggio, Elisa

    2015-12-01

    Leucine-rich repeat kinase 2 (LRRK2) is a causative gene for Parkinson's disease, but the physiological function and the mechanism(s) by which the cellular activity of LRRK2 is regulated are poorly understood. Here, we identified p21-activated kinase 6 (PAK6) as a novel interactor of the GTPase/ROC domain of LRRK2. p21-activated kinases are serine-threonine kinases that serve as targets for the small GTP binding proteins Cdc42 and Rac1 and have been implicated in different morphogenetic processes through remodeling of the actin cytoskeleton such as synapse formation and neuritogenesis. Using an in vivo neuromorphology assay, we show that PAK6 is a positive regulator of neurite outgrowth and that LRRK2 is required for this function. Analyses of post-mortem brain tissue from idiopathic and LRRK2 G2019S carriers reveal an increase in PAK6 activation state, whereas knock-out LRRK2 mice display reduced PAK6 activation and phosphorylation of PAK6 substrates. Taken together, these results support a critical role of LRRK2 GTPase domain in cytoskeletal dynamics in vivo through the novel interactor PAK6, and provide a valuable platform to unravel the mechanism underlying LRRK2-mediated pathophysiology. We propose p21-activated kinase 6 (PAK6) as a novel interactor of leucine-rich repeat kinase 2 (LRRK2), a kinase involved in Parkinson's disease (PD). In health, PAK6 regulates neurite complexity in the brain and LRRK2 is required for its function, (a) whereas PAK6 is aberrantly activated in LRRK2-linked PD brain (b) suggesting that LRRK2 toxicity is mediated by PAK6. PMID:26375402

  11. Dynamics of Turing Patterns under Spatiotemporal Forcing

    NASA Astrophysics Data System (ADS)

    Rüdiger, S.; Míguez, D. G.; Muñuzuri, A. P.; Sagués, F.; Casademunt, J.

    2003-03-01

    We study, both theoretically and experimentally, the dynamical response of Turing patterns to a spatiotemporal forcing in the form of a traveling-wave modulation of a control parameter. We show that from strictly spatial resonance, it is possible to induce new, generic dynamical behaviors, including temporally modulated traveling waves and localized traveling solitonlike solutions. The latter make contact with the soliton solutions of Coullet [

    Phys. Rev. Lett.PRLTAO0031-9007 56, 724 (1986)
    ] and generalize them. The stability diagram for the different propagating modes in the Lengyel-Epstein model is determined numerically. Direct observations of the predicted solutions in experiments carried out with light modulations in the photosensitive chlorine dioxide-iodine-malonic acid reaction are also reported.

  12. Fluid flow dynamics under location uncertainty

    NASA Astrophysics Data System (ADS)

    Mémin, Etienne

    2014-03-01

    We present a derivation of a stochastic model of Navier Stokes equations that relies on a decomposition of the velocity fields into a differentiable drift component and a time uncorrelated uncertainty random term. This type of decomposition is reminiscent in spirit to the classical Reynolds decomposition. However, the random velocity fluctuations considered here are not differentiable with respect to time, and they must be handled through stochastic calculus. The dynamics associated with the differentiable drift component is derived from a stochastic version of the Reynolds transport theorem. It includes in its general form an uncertainty dependent "subgrid" bulk formula that cannot be immediately related to the usual Boussinesq eddy viscosity assumption constructed from thermal molecular agitation analogy. This formulation, emerging from uncertainties on the fluid parcels location, explains with another viewpoint some subgrid eddy diffusion models currently used in computational fluid dynamics or in geophysical sciences and paves the way for new large-scales flow modelling. We finally describe an applications of our formalism to the derivation of stochastic versions of the Shallow water equations or to the definition of reduced order dynamical systems.

  13. Nucleosome repositioning underlies dynamic gene expression.

    PubMed

    Nocetti, Nicolas; Whitehouse, Iestyn

    2016-03-15

    Nucleosome repositioning at gene promoters is a fundamental aspect of the regulation of gene expression. However, the extent to which nucleosome repositioning is used within eukaryotic genomes is poorly understood. Here we report a comprehensive analysis of nucleosome positions as budding yeast transit through an ultradian cycle in which expression of >50% of all genes is highly synchronized. We present evidence of extensive nucleosome repositioning at thousands of gene promoters as genes are activated and repressed. During activation, nucleosomes are relocated to allow sites of general transcription factor binding and transcription initiation to become accessible. The extent of nucleosome shifting is closely related to the dynamic range of gene transcription and generally related to DNA sequence properties and use of the coactivators TFIID or SAGA. However, dynamic gene expression is not limited to SAGA-regulated promoters and is an inherent feature of most genes. While nucleosome repositioning occurs pervasively, we found that a class of genes required for growth experience acute nucleosome shifting as cells enter the cell cycle. Significantly, our data identify that the ATP-dependent chromatin-remodeling enzyme Snf2 plays a fundamental role in nucleosome repositioning and the expression of growth genes. We also reveal that nucleosome organization changes extensively in concert with phases of the cell cycle, with large, regularly spaced nucleosome arrays being established in mitosis. Collectively, our data and analysis provide a framework for understanding nucleosome dynamics in relation to fundamental DNA-dependent transactions. PMID:26966245

  14. Dynamics of Hyperbranched Polymers under Confinement

    NASA Astrophysics Data System (ADS)

    Androulaki, Krystallenia; Chrissopoulou, Kiriaki; Anastasiadis, Spiros H.; Prevosto, Daniele; Labardi, Massimiliano

    2015-03-01

    The effect of severe confinement on the dynamics of three different generations of hyperbranched polyesters (Boltorns) is investigated by Dielectric Spectroscopy. The polymers are intercalated within the galleries of natural Na+-MMT, thus, forming 1nm polymer films confined between solid walls. The Tg's of the polymers determined by DSC show a clear dependence on the generation whereas the transition is completely suppressed when all the polymer chains are intercalated. The dynamic investigation of the bulk polymers reveals two sub-Tg processes, with similar behavior for the three polymers with the segmental relaxation observed above the Tg of each. For the nanocomposites, where all polymers are severely confined, the dynamics show significant differences compared to that of the bulk polymers. The sub-Tg processes are similar for the three generations but significantly faster and with weaker temperature dependence than those in the bulk. The segmental process appears at temperatures below the bulk polymer Tg, it exhibits an Arrhenius temperature dependence and shows differences for the three generations. A slow process that appears at higher temperatures is due to interfacial polarization. Co-financed by the EU and Greek funds through the Operational Program ``Education and Lifelong Learning'' of the NSRF-Research Funding Program: THALES-Investing in knowledge society through the Eur. Social Fund (MIS 377278) and COST Action MP0902-COINAPO.

  15. Preparation of embryonic retinal explants to study CNS neurite growth.

    PubMed

    Hanea, Sonia T; Shanmugalingam, Ushananthini; Fournier, Alyson E; Smith, Patrice D

    2016-05-01

    This protocol outlines the preparation of embryonic mouse retinal explants, which provides an effective technique to analyze neurite outgrowth in central nervous system (CNS) neurons. This validated ex vivo system, which displays limited neuronal death, is highly reproducible and particularly amenable to manipulation. Our previously published studies involving embryonic chick or adult mouse retinal explants were instrumental in the preparation of this protocol; aspects of these previous techniques were combined, adopted and optimized. This protocol thus permits more efficient analysis of neurite growth. Briefly, the retina is dissected from the embryonic mouse eye using precise techniques that take into account the small size of the embryonic eye. The approach applied ensures that the retinal ganglion cell (RGC) layer faces the adhesion substrate on coated cover slips. Neurite growth is clear, well-delineated and readily quantifiable. These retinal explants can therefore be used to examine the neurite growth effects elicited by potential therapeutic agents. PMID:27072342

  16. Age-dependent differences in brain tissue microstructure assessed with neurite orientation dispersion and density imaging.

    PubMed

    Merluzzi, Andrew P; Dean, Douglas C; Adluru, Nagesh; Suryawanshi, Gaurav S; Okonkwo, Ozioma C; Oh, Jennifer M; Hermann, Bruce P; Sager, Mark A; Asthana, Sanjay; Zhang, Hui; Johnson, Sterling C; Alexander, Andrew L; Bendlin, Barbara B

    2016-07-01

    Human aging is accompanied by progressive changes in executive function and memory, but the biological mechanisms underlying these phenomena are not fully understood. Using neurite orientation dispersion and density imaging, we sought to examine the relationship between age, cellular microstructure, and neuropsychological scores in 116 late middle-aged, cognitively asymptomatic participants. Results revealed widespread increases in the volume fraction of isotropic diffusion and localized decreases in neurite density in frontal white matter regions with increasing age. In addition, several of these microstructural alterations were associated with poorer performance on tests of memory and executive function. These results suggest that neurite orientation dispersion and density imaging is capable of measuring age-related brain changes and the neural correlates of poorer performance on tests of cognitive functioning, largely in accordance with published histological findings and brain-imaging studies of people of this age range. Ultimately, this study sheds light on the processes underlying normal brain development in adulthood, knowledge that is critical for differentiating healthy aging from changes associated with dementia. PMID:27255817

  17. Serum- and substratum-dependent modulation of neuritic growth.

    PubMed

    Skaper, S D; Selak, I; Varon, S

    1983-01-01

    Explants of embryonic day 8 (E8) chicken dorsal root ganglia (DRG) have been cultured with medium containing serum or the serum-free supplement N1 on one of three substrata: collagen, polyornithine (PORN), or PORN exposed to a polyornithine-binding neurite-promoting factor (PNPF-PORN). Replicate cultures were maintained with or without nerve growth factor (NGF). NGF elicited its classical neuritic outgrowth on all three substrata in serum-containing or serum-free medium. In the absence of NGF, however, a gradation of increasing neurite growth was seen with: PNPF-PORN greater than PORN greater than collagen. This response occurred in both media. In addition, the neuritic halo in each instance was markedly more developed in the absence of serum, especially on PNPF-PORN. Nonneuronal behaviors reflected both serum and substratum influences: thus, nonneuronal outgrowth consisted mainly of flat cells with serum and collagen, was nonexistent with serum and PORN or PNPF-PORN, and involved mostly Schwann-like scattered cells in the absence of serum on any one substratum. The serum-dependent behaviors of ganglionic neurites were examined further with explants from chicken E11 sympathetic ganglia. A single substratum was used (PORN), without exogenous trophic factor. Neurite outgrowth was depressed by the presence of fetal calf serum, thus supporting the generality of this phenomenon. Lastly, PC12 cells, a clonal line of rat pheochromocytoma, will grow neurites in the presence of NGF after 48 hr in serum-free, but not serum-containing media. Addition of serum to serum-free cultures at this time results in the rapid and complete retraction of neurites. PMID:6876195

  18. Dynamics of evolutionary radiation under ecological neutrality.

    PubMed

    Suzuki, Takanori Mizuno; Chiba, Satoshi

    2016-10-01

    The most spectacular phenomenon of evolutionary biota is the explosive radiation that occurs in depauperate environments in which there are fewer competitors and predators, such as oceanic islands and crater lakes. Adaptation to divergent niches has been proposed as a major cause for this accelerated speciation. Here, we show that neutral mutation, genetic drift, and neutral community dynamics are sufficient to lead to radiation. In addition, these processes yield overshooting dynamics with a decline in species richness in the later stages of radiation. We constructed an ecologically neutral model for a community on an island with a uniform environment. For the speciation process, we introduced a null model with minimal assumptions in which the incompatibilities between alleles in different lineages evolve by a random accumulation of mutations via genetic drift. Our simulations showed that the speciation rate, extinction rate and genetic variation of the species colonizing the island rapidly increased to a sharp peak followed by a decrease that approached zero. Because the extinction rate reached a peak later than the speciation rate, the species richness initially increased, but declined in the later stage, exhibiting "overshooting". The highest species richness was found for the largest island at the largest initial population size. Accordingly, speciation is accelerated by the large population size of depauperate biota, whereas it is decelerated with increasing species richness from the decreasing population size. Explosive radiation without ecological divergence can occur in depauperate environments via neutral stochastic processes. PMID:27297287

  19. Natural neural projection dynamics underlying social behavior.

    PubMed

    Gunaydin, Lisa A; Grosenick, Logan; Finkelstein, Joel C; Kauvar, Isaac V; Fenno, Lief E; Adhikari, Avishek; Lammel, Stephan; Mirzabekov, Julie J; Airan, Raag D; Zalocusky, Kelly A; Tye, Kay M; Anikeeva, Polina; Malenka, Robert C; Deisseroth, Karl

    2014-06-19

    Social interaction is a complex behavior essential for many species and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social, but not novel object, interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type 1 dopamine receptor signaling downstream in the NAc. Direct observation of deep projection-specific activity in this way captures a fundamental and previously inaccessible dimension of mammalian circuit dynamics. PMID:24949967

  20. Natural neural projection dynamics underlying social behavior

    PubMed Central

    Gunaydin, Lisa A.; Grosenick, Logan; Finkelstein, Joel C.; Kauvar, Isaac V.; Fenno, Lief E.; Adhikari, Avishek; Lammel, Stephan; Mirzabekov, Julie J.; Airan, Raag D.; Zalocusky, Kelly A.; Tye, Kay M.; Anikeeva, Polina; Malenka, Robert C.; Deisseroth, Karl

    2014-01-01

    Social interaction is a complex behavior essential for many species, and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically- and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior. Fiber photometry revealed that activity dynamics of a ventral tegmental area (VTA)-to-nucleus accumbens (NAc) projection could encode and predict key features of social but not novel-object interaction. Consistent with this observation, optogenetic control of cells specifically contributing to this projection was sufficient to modulate social behavior, which was mediated by type-1 dopamine receptor signaling downstream in the NAc. Direct observation of projection-specific activity in this way captures a fundamental and previously inaccessible dimension of circuit dynamics. PMID:24949967

  1. Dynamics of active cellular response under stress

    NASA Astrophysics Data System (ADS)

    de, Rumi; Zemel, Assaf; Safran, Samuel

    2008-03-01

    Forces exerted by and on adherent cells are important for many physiological processes such as wound healing and tissue formation. In addition, recent experiments have shown that stem cell differentiation is controlled, at least in part, by the elasticity of the surrounding matrix. Using a simple theoretical model that includes the forces due to both the mechanosensitive nature of cells and the elastic response of the matrix, we predict the dynamics of orientation of cells. The model predicts many features observed in measurements of cellular forces and orientation including the increase with time of the forces generated by cells in the absence of applied stress and the consequent decrease of the force in the presence of quasi-static stresses. We also explain the puzzling observation of parallel alignment of cells for static and quasi-static stresses and of nearly perpendicular alignment for dynamically varying stresses. In addition, we predict the response of the cellular orientation to a sinusoidally varying applied stress as a function of frequency. The dependence of the cell orientation angle on the Poisson ratio of the surrounding material can be used to distinguish systems in which cell activity is controlled by stress from those where cell activity is controlled by strain. Reference: Nature Physics, vol. 3, pp 655 (2007).

  2. Human central nervous system myelin inhibits neurite outgrowth.

    PubMed

    Ng, W P; Cartel, N; Roder, J; Roach, A; Lozano, A

    1996-05-13

    In vitro and animal studies have identified molecules in mammalian CNS myelin which inhibit neuritic extension and which may be responsible, at least in part, for the lack of axonal regeneration after injury in the injured brain, optic nerve and spinal cord. To determine whether such inhibitory activity may be present in human CNS myelin, we used a bioassay to characterize neurite outgrowth on this substrate. Human CNS myelin strongly inhibited neuritic outgrowth from newborn rat dorsal root ganglion neurons and NG-108-15 cells, a neuroblastoma-glioma hybrid cell line. Similar but less potent inhibitory activity was identified in human gray matter. The CNS myelin inhibition of neuritic outgrowth appeared to be dependent on direct contact between the myelin substrate and neurites. The inhibitory activity in human CNS myelin closely resembled that described in adult rodents. Inhibition of neurite growth by human CNS myelin in this in vitro bioassay mirrors the lack of regeneration in vivo and can be used as a model to develop strategies designed to enhance axonal regeneration and neural recovery. PMID:8782892

  3. Space Station flexible dynamics under plume impingement

    NASA Technical Reports Server (NTRS)

    Williams, Trevor

    1993-01-01

    Assembly of the Space Station requires numerous construction flights by the Space Shuttle. A particularly challenging problem is that of control of each intermediate station configuration when the shuttle orbiter is approaching it to deliver the next component. The necessary braking maneuvers cause orbiter thruster plumes to impinge on the station, especially its solar arrays. This in turn causes both overall attitude errors and excitation of flexible-body vibration modes. These plume loads are predicted to lead to CMG saturation during the approach of the orbiter to the SC-5 station configuration, necessitating the use of the station RCS jets for desaturation. They are also expected to lead to significant excitation of solar array vibrations. It is therefore of great practical importance to investigate the effects of plume loads on the flexible dynamics of station configuration SC-5 as accurately as possible. However, this system possesses a great many flexible modes (89 below 5 rad/s), making analysis time-consuming and complicated. Model reduction techniques can be used to overcome this problem, reducing the system model to one which retains only the significant dynamics, i.e. those which are strongly excited by the control inputs or plume disturbance forces and which strongly couple with the measured outputs. The particular technique to be used in this study is the subsystem balancing approach which was previously developed by the present investigator. This method is very efficient computationally. Furthermore, it gives accurate results even for the difficult case where the structure has many closed-spaced natural frequencies, when standard modal truncation can give misleading results. Station configuration SC-5 is a good example of such a structure.

  4. Space Station flexible dynamics under plume impingement

    NASA Astrophysics Data System (ADS)

    Williams, Trevor

    1993-12-01

    Assembly of the Space Station requires numerous construction flights by the Space Shuttle. A particularly challenging problem is that of control of each intermediate station configuration when the shuttle orbiter is approaching it to deliver the next component. The necessary braking maneuvers cause orbiter thruster plumes to impinge on the station, especially its solar arrays. This in turn causes both overall attitude errors and excitation of flexible-body vibration modes. These plume loads are predicted to lead to CMG saturation during the approach of the orbiter to the SC-5 station configuration, necessitating the use of the station RCS jets for desaturation. They are also expected to lead to significant excitation of solar array vibrations. It is therefore of great practical importance to investigate the effects of plume loads on the flexible dynamics of station configuration SC-5 as accurately as possible. However, this system possesses a great many flexible modes (89 below 5 rad/s), making analysis time-consuming and complicated. Model reduction techniques can be used to overcome this problem, reducing the system model to one which retains only the significant dynamics, i.e. those which are strongly excited by the control inputs or plume disturbance forces and which strongly couple with the measured outputs. The particular technique to be used in this study is the subsystem balancing approach which was previously developed by the present investigator. This method is very efficient computationally. Furthermore, it gives accurate results even for the difficult case where the structure has many closed-spaced natural frequencies, when standard modal truncation can give misleading results. Station configuration SC-5 is a good example of such a structure.

  5. Neural Dynamics Underlying Event-Related Potentials

    NASA Technical Reports Server (NTRS)

    Shah, Ankoor S.; Bressler, Steven L.; Knuth, Kevin H.; Ding, Ming-Zhou; Mehta, Ashesh D.; Ulbert, Istvan; Schroeder, Charles E.

    2003-01-01

    There are two opposing hypotheses about the brain mechanisms underlying sensory event-related potentials (ERPs). One holds that sensory ERPs are generated by phase resetting of ongoing electroencephalographic (EEG) activity, and the other that they result from signal averaging of stimulus-evoked neural responses. We tested several contrasting predictions of these hypotheses by direct intracortical analysis of neural activity in monkeys. Our findings clearly demonstrate evoked response contributions to the sensory ERP in the monkey, and they suggest the likelihood that a mixed (Evoked/Phase Resetting) model may account for the generation of scalp ERPs in humans.

  6. Granular dynamics under shear with deformable boundaries

    NASA Astrophysics Data System (ADS)

    Geller, Drew; Backhaus, Scott; Ecke, Robert

    2015-03-01

    Granular materials under shear develop complex patterns of stress as the result of granular positional rearrangements under an applied load. We consider the simple planar shear of a quasi two-dimensional granular material consisting of bi-dispersed nylon cylinders confined between deformable boundaries. The aspect ratio of the gap width to total system length is 50, and the ratio of particle diameter to gap width is about 10. This system, designed to model a long earthquake fault with long range elastic coupling through the plates, is an interesting model system for understanding effective granular friction because it essentially self tunes to the jamming condition owing to the hardness of the grains relative to that of the boundary material, a ratio of more than 1000 in elastic moduli. We measure the differential strain displacements of the plates, the inhomogeneous stress distribution in the plates, the positions and angular orientations of the individual grains, and the shear force, all as functions of the applied normal stress. There is significant stick-slip motion in this system that we quantify through our quantitative measurements of both the boundary and the grain motion, resulting in a good characterization of this sheared 2D hard sphere system.

  7. Concentration Dynamics of Nanoparticles under a Periodic Light Field

    NASA Astrophysics Data System (ADS)

    Livashvili, A. I.; Krishtop, V. V.; Bryukhanova, T. N.; Kostina, G. V.

    Using a system of heat and mass balance equations, we study the dynamics of the concentration of nanoparticles in nanofluids under the influence of a periodic light field. The review will be based on the thermal convection.

  8. Pulsed electromagnetic fields potentiate neurite outgrowth in the dopaminergic MN9D cell line.

    PubMed

    Lekhraj, Rukmani; Cynamon, Deborah E; DeLuca, Stephanie E; Taub, Eric S; Pilla, Arthur A; Casper, Diana

    2014-06-01

    Pulsed electromagnetic fields (PEMF) exert biological effects and are in clinical use to facilitate bone repair and wound healing. Research has demonstrated that PEMF can induce signaling molecules and growth factors, molecules that play important roles in neuronal differentiation. Here, we tested the effects of a low-amplitude, nonthermal, pulsed radiofrequency signal on morphological neuronal differentiation in MN9D, a dopaminergic cell line. Cells were plated in medium with 10% fetal calf serum. After 1 day, medium was replaced with serum-containing medium, serum-free medium, or medium supplemented with dibutyryl cyclic adenosine monophosphate (Bt2 cAMP), a cAMP analog known to induce neurite outgrowth. Cultures were divided into groups and treated with PEMF signals for either 30 min per day or continuously for 15 min every hour for 3 days. Both serum withdrawal and Bt2 cAMP significantly increased neurite length. PEMF treatment similarly increased neurite length under both serum-free and serum-supplemented conditions, although to a lesser degree in the presence of serum, when continuous treatments had greater effects. PEMF signals also increased cell body width, indicating neuronal maturation, and decreased protein content, suggesting that this treatment was antimitotic, an effect reversed by the inhibitor of cAMP formation dideoxyadenosine. Bt2 cAMP and PEMF effects were not additive, suggesting that neurite elongation was achieved through a common pathway. PEMF signals increased cAMP levels from 3 to 5 hr after treatment, supporting this mechanism of action. Although neuritogenesis is considered a developmental process, it may also represent the plasticity required to form and maintain synaptic connections throughout life. PMID:24523147

  9. Neuroprotective effects of ginsenoside Rb1 on hippocampal neuronal injury and neurite outgrowth

    PubMed Central

    Liu, Juan; He, Jing; Huang, Liang; Dou, Ling; Wu, Shuang; Yuan, Qionglan

    2014-01-01

    Ginsenoside Rb1 has been reported to exert anti-aging and anti-neurodegenerative effects. In the present study, we investigate whether ginsenoside Rb1 is involved in neurite outgrowth and neuroprotection against damage induced by amyloid beta (25–35) in cultured hippocampal neurons, and explore the underlying mechanisms. Ginsenoside Rb1 significantly increased neurite outgrowth in hippocampal neurons, and increased the expression of phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2. These effects were abrogated by API-2 and PD98059, inhibitors of the signaling proteins Akt and MEK. Additionally, cultured hippocampal neurons were exposed to amyloid beta (25–35) for 30 minutes; ginsenoside Rb1 prevented apoptosis induced by amyloid beta (25–35), and this effect was blocked by API-2 and PD98059. Furthermore, ginsenoside Rb1 significantly reversed the reduction in phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2 levels induced by amyloid beta (25–35), and API-2 neutralized the effect of ginsenoside Rb1. The present results indicate that ginsenoside Rb1 enhances neurite outgrowth and protects against neurotoxicity induced by amyloid beta (25–35) via a mechanism involving Akt and extracellular signal-regulated kinase 1/2 signaling. PMID:25206916

  10. FGF inhibits neurite outgrowth over monolayers of astrocytes and fibroblasts expressing transfected cell adhesion molecules.

    PubMed

    Williams, E J; Mittal, B; Walsh, F S; Doherty, P

    1995-11-01

    We have cultured cerebellar neurons on monolayers of cortical astrocytes in control medium or medium containing recombinant basic fibroblast growth factor (FGF). FGF was found to inhibit neurite outgrowth, with a significant effect seen at 0.5 ng/ml and a maximal effect at 10 ng/ml. FGF increased the production of arachidonic acid (AA) in cerebellar neurons, and when added directly to cultures or generated endogenously via activation of phospholipase A2 using melittin, this second messenger could mimic the inhibitory effect of FGF. FGF and AA could also specifically inhibit neurite outgrowth stimulated by three cell adhesion molecules (NCAM, N-cadherin and L1) expressed in transfected fibroblasts, or in the case of L1 bound to a tissue culture substratum. These data demonstrate that, in certain cellular contexts, FGF can act as an inhibitory cue for axonal growth and that arachidonic acid is the second messenger responsible for this activity. We discuss the possibility that arachidonic acid inhibits neurite outgrowth by desensitising the second messenger pathway underlying neuronal responsiveness to cell adhesion molecules. PMID:8586663

  11. Dynamical evolution of sand ripples under water.

    PubMed

    Stegner, A; Wesfreid, J E

    1999-10-01

    We have performed an experimental study on the evolution of sand ripples formed under the action of an oscillatory flow. An annular sand-water cell was used in order to investigate a wide range of parameters. The sand ripples follow an irreversible condensation mechanism from small to large wavelength until a final state is reached. The wavelength and the shape of these stable sand patterns are mainly governed by the fluid displacement and the static angle of the granular media. A strong hysteresis affects the evolution of steep ripples. When the acceleration of the sand bed reaches a critical value, the final pattern is modified by the superficial fluidization of the sand layer. PMID:11970264

  12. Stochastic population dynamics under resource constraints

    NASA Astrophysics Data System (ADS)

    Gavane, Ajinkya S.; Nigam, Rahul

    2016-06-01

    This paper investigates the population growth of a certain species in which every generation reproduces thrice over a period of predefined time, under certain constraints of resources needed for survival of population. We study the survival period of a species by randomizing the reproduction probabilities within a window at same predefined ages and the resources are being produced by the working force of the population at a variable rate. This randomness in the reproduction rate makes the population growth stochastic in nature and one cannot predict the exact form of evolution. Hence we study the growth by running simulations for such a population and taking an ensemble averaged over 500 to 5000 such simulations as per the need. While the population reproduces in a stochastic manner, we have implemented a constraint on the amount of resources available for the population. This is important to make the simulations more realistic. The rate of resource production then is tuned to find the rate which suits the survival of the species. We also compute the mean life time of the species corresponding to different resource production rate. Study for these outcomes in the parameter space defined by the reproduction probabilities and rate of resource production is carried out.

  13. Blurred Star Image Processing for Star Sensors under Dynamic Conditions

    PubMed Central

    Zhang, Weina; Quan, Wei; Guo, Lei

    2012-01-01

    The precision of star point location is significant to identify the star map and to acquire the aircraft attitude for star sensors. Under dynamic conditions, star images are not only corrupted by various noises, but also blurred due to the angular rate of the star sensor. According to different angular rates under dynamic conditions, a novel method is proposed in this article, which includes a denoising method based on adaptive wavelet threshold and a restoration method based on the large angular rate. The adaptive threshold is adopted for denoising the star image when the angular rate is in the dynamic range. Then, the mathematical model of motion blur is deduced so as to restore the blurred star map due to large angular rate. Simulation results validate the effectiveness of the proposed method, which is suitable for blurred star image processing and practical for attitude determination of satellites under dynamic conditions. PMID:22778666

  14. Crack tip blunting and cleavage under dynamic conditions

    NASA Astrophysics Data System (ADS)

    Rajan, V. P.; Curtin, W. A.

    2016-05-01

    In structural materials with both brittle and ductile phases, cracks often initiate within the brittle phase and propagate dynamically towards the ductile phase. The macroscale, quasistatic toughness of the material thus depends on the outcome of this microscale, dynamic process. Indeed, dynamics has been hypothesized to suppress dislocation emission, which may explain the occurrence of brittle transgranular fracture in mild steels at low temperatures (Lin et al., 1987). Here, crack tip blunting and cleavage under dynamic conditions are explored using continuum mechanics and molecular dynamics simulations. The focus is on two questions: (1) whether dynamics can affect the energy barriers for dislocation emission and cleavage, and (2) what happens in the dynamic "overloaded" situation, in which both processes are energetically possible. In either case, dynamics may shift the balance between brittle cleavage and ductile blunting, thereby affecting the intrinsic ductility of the material. To explore these effects in simulation, a novel interatomic potential is used for which the intrinsic ductility is tunable, and a novel simulation technique is employed, termed as a "dynamic cleavage test", in which cracks can be run dynamically at a prescribed energy release rate into a material. Both theory and simulation reveal, however, that the intrinsic ductility of a material is unaffected by dynamics. The energy barrier to dislocation emission appears to be identical in quasi-static and dynamic conditions, and, in the overloaded situation, ductile crack tip behavior ultimately prevails since a single emission event can blunt and arrest the crack, preventing further cleavage. Thus, dynamics cannot embrittle a ductile material, and the origin of brittle failure in certain alloys (e.g., mild steels) appears unrelated to dynamic effects at the crack tip.

  15. Alpha-Synuclein affects neurite morphology, autophagy, vesicle transport and axonal degeneration in CNS neurons

    PubMed Central

    Koch, J C; Bitow, F; Haack, J; d'Hedouville, Z; Zhang, J-N; Tönges, L; Michel, U; Oliveira, L M A; Jovin, T M; Liman, J; Tatenhorst, L; Bähr, M; Lingor, P

    2015-01-01

    Many neuropathological and experimental studies suggest that the degeneration of dopaminergic terminals and axons precedes the demise of dopaminergic neurons in the substantia nigra, which finally results in the clinical symptoms of Parkinson disease (PD). The mechanisms underlying this early axonal degeneration are, however, still poorly understood. Here, we examined the effects of overexpression of human wildtype alpha-synuclein (αSyn-WT), a protein associated with PD, and its mutant variants αSyn-A30P and -A53T on neurite morphology and functional parameters in rat primary midbrain neurons (PMN). Moreover, axonal degeneration after overexpression of αSyn-WT and -A30P was analyzed by live imaging in the rat optic nerve in vivo. We found that overexpression of αSyn-WT and of its mutants A30P and A53T impaired neurite outgrowth of PMN and affected neurite branching assessed by Sholl analysis in a variant-dependent manner. Surprisingly, the number of primary neurites per neuron was increased in neurons transfected with αSyn. Axonal vesicle transport was examined by live imaging of PMN co-transfected with EGFP-labeled synaptophysin. Overexpression of all αSyn variants significantly decreased the number of motile vesicles and decelerated vesicle transport compared with control. Macroautophagic flux in PMN was enhanced by αSyn-WT and -A53T but not by αSyn-A30P. Correspondingly, colocalization of αSyn and the autophagy marker LC3 was reduced for αSyn-A30P compared with the other αSyn variants. The number of mitochondria colocalizing with LC3 as a marker for mitophagy did not differ among the groups. In the rat optic nerve, both αSyn-WT and -A30P accelerated kinetics of acute axonal degeneration following crush lesion as analyzed by in vivo live imaging. We conclude that αSyn overexpression impairs neurite outgrowth and augments axonal degeneration, whereas axonal vesicle transport and autophagy are severely altered. PMID:26158517

  16. Shoc2/Sur8 Protein Regulates Neurite Outgrowth

    PubMed Central

    Leon, Gonzalo; Sanchez-Ruiloba, Lucia; Perez-Rodriguez, Andrea; Gragera, Teresa; Martinez, Natalia; Hernandez, Silvia; Anta, Berta; Calero, Olga; Garcia-Dominguez, Carlota A.; Dura, Lara M.; Peña-Jimenez, Daniel; Castro, Judit; Zarich, Natasha; Sanchez-Gomez, Pilar; Calero, Miguel; Iglesias, Teresa; Oliva, Jose L.; Rojas, Jose M.

    2014-01-01

    The Shoc2 protein has been implicated in the positive regulation of the Ras-ERK pathway by increasing the functional binding interaction between Ras and Raf, leading to increased ERK activity. Here we found that Shoc2 overexpression induced sustained ERK phosphorylation, notably in the case of EGF stimulation, and Shoc2 knockdown inhibited ERK activation. We demonstrate that ectopic overexpression of human Shoc2 in PC12 cells significantly promotes neurite extension in the presence of EGF, a stimulus that induces proliferation rather than differentiation in these cells. Finally, Shoc2 depletion reduces both NGF-induced neurite outgrowth and ERK activation in PC12 cells. Our data indicate that Shoc2 is essential to modulate the Ras-ERK signaling outcome in cell differentiation processes involved in neurite outgrowth. PMID:25514808

  17. Decentralized optimal control of dynamical systems under uncertainty

    NASA Astrophysics Data System (ADS)

    Gabasov, R.; Dmitruk, N. M.; Kirillova, F. M.

    2011-07-01

    The problem of optimal control of a group of interconnected dynamical objects under uncertainty is considered. The cases are examined in which the centralized control of the group of objects is impossible due to delay in the channel for information exchange between the group members. Optimal self-control algorithms in real time for each dynamical object are proposed. Various types of a priori and current information about the behavior of the group members and about uncertainties in the system are examined. The proposed methods supplement the earlier developed optimal control methods for an individual dynamical system and the methods of decentralized optimal control of deterministic objects. The results are illustrated with examples.

  18. Material Stiffness Effects on Neurite Alignment to Photopolymerized Micropatterns

    PubMed Central

    2015-01-01

    The ability to direct neurite growth into a close proximity of stimulating elements of a neural prosthesis, such as a retinal or cochlear implant (CI), may enhance device performance and overcome current spatial signal resolution barriers. In this work, spiral ganglion neurons (SGNs), which are the target neurons to be stimulated by CIs, were cultured on photopolymerized micropatterns with varied matrix stiffnesses to determine the effect of rigidity on neurite alignment to physical cues. Micropatterns were generated on methacrylate thin film surfaces in a simple, rapid photopolymerization step by photomasking the prepolymer formulation with parallel line–space gratings. Two methacrylate series, a nonpolar HMA-co-HDDMA series and a polar PEGDMA-co-EGDMA series, with significantly different surface wetting properties were evaluated. Equivalent pattern periodicity was maintained across each methacrylate series based on photomask band spacing, and the feature amplitude was tuned to a depth of 2 μm amplitude for all compositions using the temporal control afforded by the UV curing methodology. The surface morphology was characterized by scanning electron microscopy and white light interferometry. All micropatterned films adsorb similar amounts of laminin from solution, and no significant difference in SGN survival was observed when the substrate compositions were compared. SGN neurite alignment significantly increases with increasing material modulus for both methacrylate series. Interestingly, SGN neurites respond to material stiffness cues that are orders of magnitude higher (GPa) than what is typically ascribed to neural environments (kPa). The ability to understand neurite response to engineered physical cues and mechanical properties such as matrix stiffness will allow the development of advanced biomaterials that direct de novo neurite growth to address the spatial signal resolution limitations of current neural prosthetics. PMID:25211120

  19. Neuroprotective copper bis(thiosemicarbazonato) complexes promote neurite elongation.

    PubMed

    Bica, Laura; Liddell, Jeffrey R; Donnelly, Paul S; Duncan, Clare; Caragounis, Aphrodite; Volitakis, Irene; Paterson, Brett M; Cappai, Roberto; Grubman, Alexandra; Camakaris, James; Crouch, Peter J; White, Anthony R

    2014-01-01

    Abnormal biometal homeostasis is a central feature of many neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and motor neuron disease. Recent studies have shown that metal complexing compounds behaving as ionophores such as clioquinol and PBT2 have robust therapeutic activity in animal models of neurodegenerative disease; however, the mechanism of neuroprotective action remains unclear. These neuroprotective or neurogenerative processes may be related to the delivery or redistribution of biometals, such as copper and zinc, by metal ionophores. To investigate this further, we examined the effect of the bis(thiosemicarbazonato)-copper complex, Cu(II)(gtsm) on neuritogenesis and neurite elongation (neurogenerative outcomes) in PC12 neuronal-related cultures. We found that Cu(II)(gtsm) induced robust neurite elongation in PC12 cells when delivered at concentrations of 25 or 50 nM overnight. Analogous effects were observed with an alternative copper bis(thiosemicarbazonato) complex, Cu(II)(atsm), but at a higher concentration. Induction of neurite elongation by Cu(II)(gtsm) was restricted to neurites within the length range of 75-99 µm with a 2.3-fold increase in numbers of neurites in this length range with 50 nM Cu(II)(gtsm) treatment. The mechanism of neurogenerative action was investigated and revealed that Cu(II)(gtsm) inhibited cellular phosphatase activity. Treatment of cultures with 5 nM FK506 (calcineurin phosphatase inhibitor) resulted in analogous elongation of neurites compared to 50 nM Cu(II)(gtsm), suggesting a potential link between Cu(II)(gtsm)-mediated phosphatase inhibition and neurogenerative outcomes. PMID:24587210

  20. Material stiffness effects on neurite alignment to photopolymerized micropatterns.

    PubMed

    Tuft, Bradley W; Zhang, Lichun; Xu, Linjing; Hangartner, Austin; Leigh, Braden; Hansen, Marlan R; Guymon, C Allan

    2014-10-13

    The ability to direct neurite growth into a close proximity of stimulating elements of a neural prosthesis, such as a retinal or cochlear implant (CI), may enhance device performance and overcome current spatial signal resolution barriers. In this work, spiral ganglion neurons (SGNs), which are the target neurons to be stimulated by CIs, were cultured on photopolymerized micropatterns with varied matrix stiffnesses to determine the effect of rigidity on neurite alignment to physical cues. Micropatterns were generated on methacrylate thin film surfaces in a simple, rapid photopolymerization step by photomasking the prepolymer formulation with parallel line-space gratings. Two methacrylate series, a nonpolar HMA-co-HDDMA series and a polar PEGDMA-co-EGDMA series, with significantly different surface wetting properties were evaluated. Equivalent pattern periodicity was maintained across each methacrylate series based on photomask band spacing, and the feature amplitude was tuned to a depth of 2 μm amplitude for all compositions using the temporal control afforded by the UV curing methodology. The surface morphology was characterized by scanning electron microscopy and white light interferometry. All micropatterned films adsorb similar amounts of laminin from solution, and no significant difference in SGN survival was observed when the substrate compositions were compared. SGN neurite alignment significantly increases with increasing material modulus for both methacrylate series. Interestingly, SGN neurites respond to material stiffness cues that are orders of magnitude higher (GPa) than what is typically ascribed to neural environments (kPa). The ability to understand neurite response to engineered physical cues and mechanical properties such as matrix stiffness will allow the development of advanced biomaterials that direct de novo neurite growth to address the spatial signal resolution limitations of current neural prosthetics. PMID:25211120

  1. The role of calsyntenin-3 in dystrophic neurite formation in Alzheimer's disease brain.

    PubMed

    Uchida, Yoko; Gomi, Fujiya

    2016-03-01

    β-Amyloid (Aβ) oligomers may play an important role in the early pathogenesis of Alzheimer's disease: cognitive impairment caused by synaptic dysfunction. Dystrophic neurites surrounding Aβ plaques, another pathological feature of Alzheimer's disease, are plaque-associated neuritic alterations preceding the appearance of synaptic loss. In the present review, we focus on the mechanism of dystrophic neurite formation by Aß oligomers, and discuss the neurotoxic role of Aβ-induced calsyntenin-3 in mediating dystrophic neurite formation. PMID:27018282

  2. Morphological identification and development of neurite in Drosophila ventral nerve cord neuropil.

    PubMed

    Gan, Guangming; Lv, Huihui; Xie, Wei

    2014-01-01

    In Drosophila, ventral nerve cord (VNC) occupies most of the larval central nervous system (CNS). However, there is little literature elaborating upon the specific types and growth of neurites as defined by their structural appearance in Drosophila larval VNC neuropil. Here we report the ultrastructural development of different types VNC neurites in ten selected time points in embryonic and larval stages utilizing transmission electron microscopy. There are four types of axonal neurites as classified by the type of vesicular content: clear vesicle (CV) neurites have clear vesicles and some T-bar structures; Dense-core vesicle (DV) neurites have dense-core vesicles and without T-bar structures; Mixed vesicle (MV) neurites have mixed vesicles and some T-bar structures; Large vesicle (LV) neurites are dominated by large, translucent spherical vesicles but rarely display T-bar structures. We found dramatic remodeling in CV neurites which can be divided into five developmental phases. The neurite is vacuolated in primary (P) phase, they have mitochondria, microtubules or big dark vesicles in the second (S) phase, and they contain immature synaptic features in the third (T) phase. The subsequent bifurcate (B) phase appears to undergo major remodeling with the appearance of the bifurcation or dendritic growth. In the final mature (M) phase, high density of commensurate synaptic vesicles are distributed around T-bar structures. There are four kinds of morphological elaboration of the CVI neurite sub-types. First, new neurite produces at the end of axon. Second, new neurite bubbles along the axon. Third, the preexisting neurite buds and develops into several neurites. The last, the bundled axons form irregularly shape neurites. Most CVI neurites in M phase have about 1.5-3 µm diameter, they could be suitable to analyze their morphology and subcellular localization of specific proteins by light microscopy, and they could serve as a potential model in CNS in vivo development

  3. Laminar stream of detergents for subcellular neurite damage in a microfluidic device: a simple tool for the study of neuroregeneration

    NASA Astrophysics Data System (ADS)

    Lee, Chang Young; Romanova, Elena V.; Sweedler, Jonathan V.

    2013-06-01

    Objective. The regeneration and repair of damaged neuronal networks is a difficult process to study in vivo, leading to the development of multiple in vitro models and techniques for studying nerve injury. Here we describe an approach for generating a well-defined subcellular neurite injury in a microfluidic device. Approach. A defined laminar stream of sodium dodecyl sulfate (SDS) was used to damage selected portions of neurites of individual neurons. The somata and neurites unaffected by the SDS stream remained viable, thereby enabling the study of neuronal regeneration. Main results. By using well-characterized neurons from Aplysia californica cultured in vitro, we demonstrate that our approach is useful in creating neurite damage, investigating neurotrophic factors, and monitoring somata migration during regeneration. Supplementing the culture medium with acetylcholinesterase (AChE) or Aplysia hemolymph facilitated the regeneration of the peptidergic Aplysia neurons within 72 h, with longer (p < 0.05) and more branched (p < 0.05) neurites than in the control medium. After the neurons were transected, their somata migrated; intriguingly, for the control cultures, the migration direction was always away from the injury site (7/7). In the supplemented cultures, the number decreased to 6/8 in AChE and 4/8 in hemolymph, with reduced migration distances in both cases. Significance. The SDS transection approach is simple and inexpensive, yet provides flexibility in studying neuroregeneration, particularly when it is important to make sure there are no retrograde signals from the distal segments affecting regeneration. Neurons are known to not only be under tension but also balanced in terms of force, and the balance is obviously disrupted by transection. Our experimental platform, verified with Aplysia, can be extended to mammalian systems, and help us gain insight into the role that neurotrophic factors and mechanical tension play during neuronal regeneration.

  4. Organic Photovoltaics and Bioelectrodes Providing Electrical Stimulation for PC12 Cell Differentiation and Neurite Outgrowth.

    PubMed

    Hsiao, Yu-Sheng; Liao, Yan-Hao; Chen, Huan-Lin; Chen, Peilin; Chen, Fang-Chung

    2016-04-13

    Current bioelectronic medicines for neurological therapies generally involve treatment with a bioelectronic system comprising a power supply unit and a bioelectrode device. Further integration of wireless and self-powered units is of practical importance for implantable bioelectronics. In this study, we developed biocompatible organic photovoltaics (OPVs) for serving as wireless electrical power supply units that can be operated under illumination with near-infrared (NIR) light, and organic bioelectronic interface (OBEI) electrode devices as neural stimulation electrodes. The OPV/OBEI integrated system is capable to provide electrical stimulation (ES) as a means of enhancing neuron-like PC12 cell differentiation and neurite outgrowth. For the OPV design, we prepared devices incorporating two photoactive material systems--β-carotene/N,N'-dioctyl-3,4,9,10-perylenedicarboximide (β-carotene/PTCDI-C8) and poly(3-hexylthiophene)/phenyl-C61-butyric acid methyl ester (P3HT/PCBM)--that exhibited open circuit voltages of 0.11 and 0.49 V, respectively, under NIR light LED (NLED) illumination. Then, we connected OBEI devices with different electrode gaps, incorporating biocompatible poly(hydroxymethylated-3,4-ethylenedioxythiophene), to OPVs to precisely tailor the direct current electric field conditions during the culturing of PC12 cells. This NIR light-driven OPV/OBEI system could be engineered to provide tunable control over the electric field (from 220 to 980 mV mm(-1)) to promote 64% enhancement in the neurite length, direct the neurite orientation on chips, or both. The OPV/OBEI integrated systems under NIR illumination appear to function as effective power delivery platforms that should meet the requirements for wirelessly offering medical ES to a portion of the nervous system; they might also be a key technology for the development of next-generation implantable bioelectronics. PMID:26999636

  5. Progression of damage and fracture in composites under dynamic loading

    NASA Technical Reports Server (NTRS)

    Minnetyan, Levon; Murthy, Pappu L. N.; Chamis, Christos C.

    1990-01-01

    A new computational simulation method is presented to evaluate the dynamic aspects of composite structural response and durability that have not been simulated previously. Composite structural behavior under any loading condition, geometry, composite system, laminate configuration, and boundary conditions can now be simulated. Structural degradation, delamination, fracture, and damage propagation are included in the simulation. An angle-plied composite plate structure under normal impact loading is used as an example to demonstrate the versatility of the simulation method.

  6. Deciphering and prediction of plant dynamics under field conditions.

    PubMed

    Izawa, Takeshi

    2015-04-01

    Elucidation of plant dynamics under fluctuating natural environments is a challenging goal in plant physiology. Recently, using a computer statistics integrating a series of transcriptome data of field-grown rice leaves during an entire crop season and several corresponding environmental data such as solar radiation and ambient temperature, most parts of transcriptome have been modeled. This reveals the detailed contributions of developmental timing, circadian clocks and each environmental factor to transcriptome dynamics in the field and can predict transcriptome dynamics under given environments. Furthermore, some traits such as flowering time in natural environments have been shown to be predicted by mathematical models based on gene-networks parameterized with data obtained in the laboratory, and phenology models refined by knowledge of molecular genetics. New molecular physiology is beginning in plant science. PMID:25706440

  7. Dynamic Tensile Strength of Coal under Dry and Saturated Conditions

    NASA Astrophysics Data System (ADS)

    Zhao, Yixin; Liu, Shimin; Jiang, Yaodong; Wang, Kai; Huang, Yaqiong

    2016-05-01

    The tensile failure characterization of dry and saturated coals under different impact loading conditions was experimentally investigated using a Split Hopkinson pressure bar. Indirect dynamic Brazilian disc tension tests for coals were carried out. The indirect tensile strengths for different bedding angles under different impact velocities, strain rates and loading rates are analyzed and discussed. A high-speed high-resolution digital camera was employed to capture and record the dynamic failure process of coal specimens. Based on the experimental results, it was found that the saturated specimens have stronger loading rate dependence than the dry specimens. The bedding angle has a smaller effect on the dynamic indirect tensile strength compared to the impact velocity. Both shear and tensile failures were observed in the tested coal specimens. Saturated coal specimens have higher indirect tensile strength than dry ones.

  8. Dynamic MRI of the TMJ under physical load

    PubMed Central

    Hopfgartner, A J; Tymofiyeva, O; Ehses, P; Rottner, K; Boldt, J; Richter, E-J; Jakob, P M

    2013-01-01

    Objectives: The objective of this study was to examine the kinematics of structures of the temporomandibular joint (TMJ) under physiological load while masticating. Methods: Radial MRI was chosen as a fast imaging method to dynamically capture the motions of the joint’s anatomy. The technique included a golden ratio-based increment angle and a sliding window reconstruction. The measurements were performed on 22 subjects with and without deformation/displacement of the intra-articular disc while they were biting on a cooled caramel toffee. Results: The reconstructed dynamic images provided sufficient information about the size and localization of the disc as well as the change of the intra-articular distance with and without loading. Conclusions: The feasibility of the golden ratio-based radial MRI technique to dynamically capture the anatomy of the TMJ under physical load was demonstrated in this initial study. PMID:23975114

  9. Protein displacements under external forces: An atomistic Langevin dynamics approach

    NASA Astrophysics Data System (ADS)

    Gnandt, David; Utz, Nadine; Blumen, Alexander; Koslowski, Thorsten

    2009-02-01

    We present a fully atomistic Langevin dynamics approach as a method to simulate biopolymers under external forces. In the harmonic regime, this approach permits the computation of the long-term dynamics using only the eigenvalues and eigenvectors of the Hessian matrix of second derivatives. We apply this scheme to identify polymorphs of model proteins by their mechanical response fingerprint, and we relate the averaged dynamics of proteins to their biological functionality, with the ion channel gramicidin A, a phosphorylase, and neuropeptide Y as examples. In an environment akin to dilute solutions, even small proteins show relaxation times up to 50 ns. Atomically resolved Langevin dynamics computations have been performed for the stretched gramicidin A ion channel.

  10. Soil Moisture Dynamics under Corn, Soybean, and Perennial Kura Clover

    NASA Astrophysics Data System (ADS)

    Ochsner, T.; Venterea, R. T.

    2009-12-01

    Rising global food and energy consumption call for increased agricultural production, whereas rising concerns for environmental quality call for farming systems with more favorable environmental impacts. Improved understanding and management of plant-soil water interactions are central to meeting these twin challenges. The objective of this research was to compare the temporal dynamics of soil moisture under contrasting cropping systems suited for the Midwestern region of the United States. Precipitation, infiltration, drainage, evapotranspiration, soil water storage, and freeze/thaw processes were measured hourly for three years in field plots of continuous corn (Zea mays L.), corn/soybean [Glycine max (L.) Merr.] rotation, and perennial kura clover (Trifolium ambiguum M. Bieb.) in southeastern Minnesota. The evapotranspiration from the perennial clover most closely followed the temporal dynamics of precipitation, resulting in deep drainage which was reduced up to 50% relative to the annual crops. Soil moisture utilization also continued later into the fall under the clover than under the annual crops. In the annual cropping systems, crop sequence influenced the soil moisture dynamics. Soybean following corn and continuous corn exhibited evapotranspiration which was 80 mm less than and deep drainage which was 80 mm greater than that of corn following soybean. These differences occurred primarily during the spring and were associated with differences in early season plant growth between the systems. In the summer, soil moisture depletion was up to 30 mm greater under corn than soybean. Crop residue also played an important role in the soil moisture dynamics. Higher amounts of residue were associated with reduced soil freezing. This presentation will highlight key aspects of the soil moisture dynamics for these contrasting cropping systems across temporal scales ranging from hours to years. The links between soil moisture dynamics, crop yields, and nutrient leaching

  11. Myelin from MAG-deficient mice is a strong inhibitor of neurite outgrowth.

    PubMed

    Ng, W P; Cartel, N; Li, C; Roder, J; Lozano, A

    1996-03-22

    Myelin-associated glycoprotein (MAG) has potent neurite outgrowth inhibitory activity in vitro. To assess the importance of MAG in the neurite outgrowth inhibitory activity in CNS myelin, we used an in vitro bioassay to characterize neurite growth on CNS myelin derived from mice carrying a null mutation of the MAG gene. Myelin proteins from MAG-deficient mice inhibited neurite outgrowth to a similar degree to the wild-type CNS myelin. These results suggest that CNS myelin molecules other than MAG exert strong inhibitory effects on the growth of neurites. PMID:8724661

  12. Fetal calf serum-mediated inhibition of neurite growth from ciliary ganglion neurons in vitro.

    PubMed

    Davis, G E; Skaper, S D; Manthorpe, M; Moonen, G; Varon, S

    1984-01-01

    Embryonic chick ciliary ganglion (CG) neurons cultured in fetal calf serum-containing medium have been previously reported to extend neurites on polyornithine (PORN) substrata precoated with a neurite-promoting factor (PNPF) from rat schwannoma-conditioned medium. On PORN substrata alone, however, no neuritic growth occurred. This was interpreted as evidence that PORN was an incompetent substratum for ciliary neuritic growth. In this study, we now find that an untreated PORN substratum allows neuritic growth in serum-free defined medium. When PNPF was added to PORN, a more rapid and extensive neuritic response occurred. After 5 hr of culture, a 60% neuritic response occurred on PNPF/PORN, whereas no neurons initiated neurites until 10-12 hr on PORN. The inhibitory effect of fetal calf serum noted above on PORN could be obtained in part by pretreating the substratum with serum for 1 hr. Maximal inhibitory effects in the PORN pretreatment were achieved after 30 min and were not further improved by treatments up to 4 hr. Bovine serum albumin was also found to inhibit neurite growth on PORN to about 60% of the inhibition obtained by an equivalent amount of serum protein. Fetal calf serum was shown to cause a 15% reduction in the percentage of neurons bearing neurites after its addition to 18-hr serum-free PORN cultures and to cause statistically significant reductions in neurite lengths measured 2 hr later. PMID:6481819

  13. Thermomechanical behavior of EUV pellicle under dynamic exposure conditions

    NASA Astrophysics Data System (ADS)

    Goldfarb, Dario L.; Bloomfield, Max O.; Colburn, Matthew

    2016-03-01

    The utilization of EUV pellicles as protective layers for EUV masks requires the use of refractory materials that can tolerate large temperature excursions due to the non-negligible absorption of EUV radiation during exposure. Additionally, the mechanical stress induced on the EUV pellicle by the thermal load is dependent on the thermal expansion of the material which can be responsible for transient wrinkling. In this study, an ultrathin (20 nm), free-standing membrane based on silicon nitride is utilized as a learning vehicle to understand the material requirements of EUV pellicles under dynamic exposure conditions that are typical of commercial EUV scanners. First, the nanoscale radiative properties (emissivity) and thermo-mechanical failure temperature of the dielectric film under vacuum conditions are experimentally investigated utilizing a pulsed ArF (193 nm) probing laser. The silicon nitride membrane is found to be marginally compatible with an equivalent 80W EUV source power under steady state illumination conditions. Next, the thermal behavior of the EUV pellicle under dynamic exposure conditions is simulated using a finite element solver. The transient temperature profile and stress distribution across the membrane under stationary state conditions are extracted for an equivalent 60W EUV power source and the pellicle wrinkling due to heating and consequent impact on CD uniformity is estimated. The present work provides a generalized methodology to anticipate the thermal response of a EUV pellicle under realistic exposure conditions.

  14. A subset of chicken statoacoustic ganglion neurites are repelled by Slit1 and Slit2

    PubMed Central

    Battisti, Andrea C.; Fantetti, Kristen N.; Moyers, Bryan A.; Fekete, Donna M.

    2014-01-01

    Mechanosensory hair cells in the chicken inner ear are innervated by bipolar afferent neurons of the statoacoustic ganglion (SAG). During development, individual SAG neurons project their peripheral process to only one of eight distinct sensory organs. These neuronal subtypes may respond differently to guidance cues as they explore the periphery in search of their target. Previous gene expression data suggested that Slit repellants might channel SAG neurites into the sensory primordia, based on the presence of robo transcripts in the neurons and the confinement of slit transcripts to the flanks of the prosensory domains. This led to the prediction that excess Slit proteins would impede the outgrowth of SAG neurites. As predicted, axonal projections to the primordium of the anterior crista were reduced 2-3 days after electroporation of either slit1 or slit2 expression plasmids into the anterior pole of the otocyst on embryonic day 3 (E3). The posterior crista afferents, which normally grow through and adjacent to slit expression domains as they are navigating towards the posterior pole of the otocyst, did not show Slit responsiveness when similarly challenged by ectopic delivery of slit to their targets. The sensitivity to ectopic Slits shown by the anterior crista afferents was more the exception than the rule: responsiveness to Slits was not observed when the entire E4 SAG was challenged with Slits for 40 hours in vitro. The corona of neurites emanating from SAG explants was unaffected by the presence of purified human Slit1 and Slit2 in the culture medium. Reduced axon outgrowth from E8 olfactory bulbs cultured under similar conditions for 24 hours confirmed bioactivity of purified human Slits on chicken neurons. In summary, differential sensitivity to Slit repellents may influence the directional outgrowth of otic axons toward either the anterior or posterior otocyst. PMID:24456709

  15. A method of measuring dynamic strain under electromagnetic forming conditions.

    PubMed

    Chen, Jinling; Xi, Xuekui; Wang, Sijun; Lu, Jun; Guo, Chenglong; Wang, Wenquan; Liu, Enke; Wang, Wenhong; Liu, Lin; Wu, Guangheng

    2016-04-01

    Dynamic strain measurement is rather important for the characterization of mechanical behaviors in electromagnetic forming process, but it has been hindered by high strain rate and serious electromagnetic interference for years. In this work, a simple and effective strain measuring technique for physical and mechanical behavior studies in the electromagnetic forming process has been developed. High resolution (∼5 ppm) of strain curves of a budging aluminum tube in pulsed electromagnetic field has been successfully measured using this technique. The measured strain rate is about 10(5) s(-1), which depends on the discharging conditions, nearly one order of magnitude of higher than that under conventional split Hopkins pressure bar loading conditions (∼10(4) s(-1)). It has been found that the dynamic fracture toughness of an aluminum alloy is significantly enhanced during the electromagnetic forming, which explains why the formability is much larger under electromagnetic forging conditions in comparison with conventional forging processes. PMID:27131683

  16. A method of measuring dynamic strain under electromagnetic forming conditions

    NASA Astrophysics Data System (ADS)

    Chen, Jinling; Xi, Xuekui; Wang, Sijun; Lu, Jun; Guo, Chenglong; Wang, Wenquan; Liu, Enke; Wang, Wenhong; Liu, Lin; Wu, Guangheng

    2016-04-01

    Dynamic strain measurement is rather important for the characterization of mechanical behaviors in electromagnetic forming process, but it has been hindered by high strain rate and serious electromagnetic interference for years. In this work, a simple and effective strain measuring technique for physical and mechanical behavior studies in the electromagnetic forming process has been developed. High resolution (˜5 ppm) of strain curves of a budging aluminum tube in pulsed electromagnetic field has been successfully measured using this technique. The measured strain rate is about 105 s-1, which depends on the discharging conditions, nearly one order of magnitude of higher than that under conventional split Hopkins pressure bar loading conditions (˜104 s-1). It has been found that the dynamic fracture toughness of an aluminum alloy is significantly enhanced during the electromagnetic forming, which explains why the formability is much larger under electromagnetic forging conditions in comparison with conventional forging processes.

  17. Dynamical weakening by fluidization under oscillatory viscous flows

    NASA Astrophysics Data System (ADS)

    Valverde, Jose Manuel

    2015-11-01

    Dynamical weakening of granular materials plays a critical role on diverse geological events such as seismic faulting and landslides. A common feature in the dynamics of these processes is the development of fluid-solid relative flows, which could lead to fluidization by hydrodynamic viscous stresses. This work is focused on analyzing hydrodynamic fluidization under oscillatory viscous flows as a possible driving mechanism for dynamical weakening. The theoretical estimations and experimental observations presented and reviewed suggest that fluidization can be greatly promoted by oscillatory viscous flows, which are usually expected in geological events involving vibration of granular materials in viscous fluids. Fluidization under oscillatory viscous flows may occur at not excessively large vibration velocities of fine particles in gases or relatively larger particles in liquids or supercritical fluids. In particular, the enhancement of fluidization by high-frequency vibrations would be a powerful mechanism to promote dynamical weakening of fine powders in dry fault gouges, failure of liquid- (or supercritical fluid-) saturated beds, and sustained fluidization of pyroclastic flows and lahars.

  18. Dynamic control of a bistable wing under aerodynamic loading

    NASA Astrophysics Data System (ADS)

    Bilgen, Onur; Arrieta, Andres F.; Friswell, Michael I.; Hagedorn, Peter

    2013-02-01

    The aerodynamic evaluation of a dynamic control technique applied to a bistable unsymmetrical cross-ply composite plate with surface bonded piezoelectric actuators is presented. The plate is clamped on one end to form a low-aspect-ratio wing. A previously proposed dynamic control method, utilizing bending resonance in different stable equilibrium positions, is used to induce snap-through between the two equilibrium states. Compared to quasi-static actuation, driving the bistable plate near resonance using surface bonded piezoelectric materials requires, theoretically, a lower peak excitation voltage to achieve snap-through. First, a set of extensive wind tunnel experiments are conducted on the passive bistable wing to understand the change in the dynamic behavior under various aerodynamic conditions. The passive wing demonstrated sufficient bending stiffness to sustain its shape under aerodynamic loading while preserving the desired bistable behavior. Next, by the use of the resonant control technique, the plate is turned into an effectively monostable structure, or alternatively, both stable equilibrium positions can be reached actively from the other stable equilibrium. Dynamic forward and reverse snap-through is demonstrated in the wind tunnel which shows both the effectiveness of the piezoelectric actuation as well as the load carrying capability of both states of the bistable wing.

  19. Phase separated microstructure and dynamics of polyurethane elastomers under strain

    NASA Astrophysics Data System (ADS)

    Iacob, Ciprian; Padsalgikar, Ajay; Runt, James

    The molecular mobility of polyurethane elastomers is of the utmost importance in establishing physical properties for uses ranging from automotive tires and shoe soles to more sophisticated aerospace and biomedical applications. In many of these applications, chain dynamics as well as mechanical properties under external stresses/strains are critical for determining ultimate performance. In order to develop a more complete understanding of their mechanical response, we explored the effect of uniaxial strain on the phase separated microstructure and molecular dynamics of the elastomers. We utilize X-ray scattering to investigate soft segment and hard domain orientation, and broadband dielectric spectroscopy for interrogation of the dynamics. Uniaxial deformation is found to significantly perturb the phase-separated microstructure and chain orientation, and results in a considerable slowing down of the dynamics of the elastomers. Attenuated total reflectance Fourier transform infrared spectroscopy measurements of the polyurethanes under uniaxial deformation are also employed and the results are quantitatively correlated with mechanical tensile tests and the degree of phase separation from small-angle X-ray scattering measurements.

  20. MiR-93 Targeting EphA4 Promotes Neurite Outgrowth from Spinal Cord Neurons.

    PubMed

    Chen, Xiaogang; Yang, Huilin; Zhou, Xiaoqing; Zhang, Lin; Lu, Xiaoqing

    2016-04-01

    The failure of neurite outgrowth in the adult mammalian spinal cord injury is thought to be attributed to the intrinsic growth ability of mature neurons. Ephrin/Eph system is a major growth regulator of many axonal guidance processes. EphA4 is expressed specifically in traumatic central nervous system (CNS) and dynamically regulate target gene expression, suggesting that it may be associated with neural regeneration. Here, we found an alteration in temporal expression of miR-93 following a contusive spinal cord injury (SCI) in adult rats. The messenger RNA (mRNA) expression level of miR-93 was upregulated and the protein expression levels of EphA4, p-Ephexin, and active RhoA were all decreased in traumatic spinal cord relative to those with an intact spinal cord. Infection of cultured spinal cord neurons (SCNs) with miR-93 mimic led to neuronal growth promotion and decreased levels of EphA4, p-Ephexin, and active RhoA protein expression. Dual-luciferase reporter assay confirmed that miR-93 bound to the three prime untranslated region (3' UTR) of EphA4 and inhibited the expression of EphA4 mRNA. These findings provide evidence that miR-93 inhibits EphA4 expression, decreased EphA4 expression could promote neurite outgrowth in SCNs due to reduced levels of p-Ephexin and active RhoA. PMID:26798048

  1. Ginsenoside Rg1 protects against neurodegeneration by inducing neurite outgrowth in cultured hippocampal neurons.

    PubMed

    Huang, Liang; Liu, Li-Feng; Liu, Juan; Dou, Ling; Wang, Ge-Ying; Liu, Xiao-Qing; Yuan, Qiong-Lan

    2016-02-01

    Ginsenoside Rg1 (Rg1) has anti-aging and anti-neurodegenerative effects. However, the mechanisms underlying these actions remain unclear. The aim of the present study was to determine whether Rg1 affects hippocampal survival and neurite outgrowth in vitro after exposure to amyloid-beta peptide fragment 25-35 (Aβ25-35), and to explore whether the extracellular signal-regulated kinase (ERK) and Akt signaling pathways are involved in these biological processes. We cultured hippocampal neurons from newborn rats for 24 hours, then added Rg1 to the medium for another 24 hours, with or without pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) family or Akt signaling pathways for a further 24 hours. We then immunostained the neurons for growth associated protein-43, and measured neurite length. In a separate experiment, we exposed cultured hippocampal neurons to Aβ25-35 for 30 minutes, before adding Rg1 for 48 hours, with or without Akt or MAPK inhibitors, and assessed neuronal survival using Hoechst 33258 staining, and phosphorylation of ERK1/2 and Akt by western blot analysis. Rg1 induced neurite outgrowth, and this effect was blocked by API-2 (Akt inhibitor) and PD98059 (MAPK/ERK kinase inhibitor), but not by SP600125 or SB203580 (inhibitors of c-Jun N-terminal kinase and p38 MAPK, respectively). Consistent with this effect, Rg1 upregulated the phosphorylation of Akt and ERK1/2; these effects were reversed by API-2 and PD98059, respectively. In addition, Rg1 significantly reversed Aβ25-35-induced apoptosis; this effect was blocked by API-2 and PD98059, but not by SP600125 or SB203580. Finally, Rg1 significantly reversed the Aβ25-35-induced decrease in Akt and ERK1/2 phosphorylation, but API-2 prevented this reversal. Our results indicate that Rg1 enhances neurite outgrowth and protects against Aβ25-35-induced damage, and that its mechanism may involve the activation of Akt and ERK1/2 signaling. PMID:27073387

  2. Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

    SciTech Connect

    Hsu, Ya-Yun; Tseng, Yu-Ting; Lo, Yi-Ching

    2013-11-01

    production and neuronal cell death. • BBR activates IGF-1/Akt/GSK-3β signaling under normal and high glucose conditions. • BBR enhances HO-1 and NGF expression through stimulating Nrf2 translocation. • BBR promotes neurite outgrowth through Nrf2-dependent pathway.

  3. Ginsenoside Rg1 protects against neurodegeneration by inducing neurite outgrowth in cultured hippocampal neurons

    PubMed Central

    Huang, Liang; Liu, Li-feng; Liu, Juan; Dou, Ling; Wang, Ge-ying; Liu, Xiao-qing; Yuan, Qiong-lan

    2016-01-01

    Ginsenoside Rg1 (Rg1) has anti-aging and anti-neurodegenerative effects. However, the mechanisms underlying these actions remain unclear. The aim of the present study was to determine whether Rg1 affects hippocampal survival and neurite outgrowth in vitro after exposure to amyloid-beta peptide fragment 25–35 (Aβ25–35), and to explore whether the extracellular signal-regulated kinase (ERK) and Akt signaling pathways are involved in these biological processes. We cultured hippocampal neurons from newborn rats for 24 hours, then added Rg1 to the medium for another 24 hours, with or without pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) family or Akt signaling pathways for a further 24 hours. We then immunostained the neurons for growth associated protein-43, and measured neurite length. In a separate experiment, we exposed cultured hippocampal neurons to Aβ25–35 for 30 minutes, before adding Rg1 for 48 hours, with or without Akt or MAPK inhibitors, and assessed neuronal survival using Hoechst 33258 staining, and phosphorylation of ERK1/2 and Akt by western blot analysis. Rg1 induced neurite outgrowth, and this effect was blocked by API-2 (Akt inhibitor) and PD98059 (MAPK/ERK kinase inhibitor), but not by SP600125 or SB203580 (inhibitors of c-Jun N-terminal kinase and p38 MAPK, respectively). Consistent with this effect, Rg1 upregulated the phosphorylation of Akt and ERK1/2; these effects were reversed by API-2 and PD98059, respectively. In addition, Rg1 significantly reversed Aβ25–35-induced apoptosis; this effect was blocked by API-2 and PD98059, but not by SP600125 or SB203580. Finally, Rg1 significantly reversed the Aβ25–35-induced decrease in Akt and ERK1/2 phosphorylation, but API-2 prevented this reversal. Our results indicate that Rg1 enhances neurite outgrowth and protects against Aβ25–35-induced damage, and that its mechanism may involve the activation of Akt and ERK1/2 signaling. PMID:27073387

  4. Relation of dynamic parameters of brick masonry fragment at fracture under static and dynamic loading

    NASA Astrophysics Data System (ADS)

    Kopanitsa, D. G.; Useinov, E. S.

    2015-01-01

    The article shows the results of experimental analysis of brick masonry fragments under static and dynamic loading. The measurements of fractures and natural vibration frequencies of samples have been carried out in the course of tests. It has been shown that at appearance of inelastic deformations and cracks, there is a change in natural vibration frequencies, received from the analysis of the corresponding spectra. Comparison of results of experiments of brick masonry fragments, received under action of static and dynamic loads has been carried out.

  5. Automated quantification of neurite outgrowth orientation distributions on patterned surfaces

    NASA Astrophysics Data System (ADS)

    Payne, Matthew; Wang, Dadong; Sinclair, Catriona M.; Kapsa, Robert M. I.; Quigley, Anita F.; Wallace, Gordon G.; Razal, Joselito M.; Baughman, Ray H.; Münch, Gerald; Vallotton, Pascal

    2014-08-01

    Objective. We have developed an image analysis methodology for quantifying the anisotropy of neuronal projections on patterned substrates. Approach. Our method is based on the fitting of smoothing splines to the digital traces produced using a non-maximum suppression technique. This enables precise estimates of the local tangents uniformly along the neurite length, and leads to unbiased orientation distributions suitable for objectively assessing the anisotropy induced by tailored surfaces. Main results. In our application, we demonstrate that carbon nanotubes arrayed in parallel bundles over gold surfaces induce a considerable neurite anisotropy; a result which is relevant for regenerative medicine. Significance. Our pipeline is generally applicable to the study of fibrous materials on 2D surfaces and should also find applications in the study of DNA, microtubules, and other polymeric materials.

  6. General polytropic dynamic cylinder under self-gravity

    NASA Astrophysics Data System (ADS)

    Lou, Yu-Qing

    2015-12-01

    We explore self-similar hydrodynamics of general polytropic (GP) and isothermal cylinders of infinite length with axial uniformity and axisymmetry under self-gravity. Specific entropy conservation along streamlines serves as the dynamic equation of state. Together with possible axial flows, we construct classes of analytic and semi-analytic non-linear dynamic solutions for either cylindrical expansion or contraction radially by solving cylindrical Lane-Emden equations. By extensive numerical explorations and fitting trials in reference to asymptotes derived for large index n, we infer several convenient empirical formulae for characteristic solution properties of cylindrical Lane-Emden equations in terms of n values. A new type of asymptotic solutions for small x is also derived in the Appendix. These analyses offer hints for self-similar dynamic evolution of molecular filaments for forming protostars, brown dwarfs and gaseous planets and of large-scale gaseous arms or starburst rings in (barred) spiral galaxies for forming young massive stars. Such dynamic solutions are necessary starting background for further three-dimensional (in)stability analysis of various modes. They may be used to initialize numerical simulations and serve as important benchmarks for testing numerical codes. Such GP formalism can be further generalized to include magnetic field for a GP magnetohydrodynamic analysis.

  7. Alignment and Stiffening of Liquid Crystal Elastomers under Dynamic Compression

    NASA Astrophysics Data System (ADS)

    Agrawal, Aditya; Patra, Prabir; Ajayan, Pulickel; Chapman, Walter; Verduzco, Rafael

    2013-03-01

    Biological tissues have the remarkable ability to remodel and repair in response to disease, injury, and mechanical stresses, a phenomenon known ``functional adaptation'' or ``remodeling''. Herein, we report similar behavior in polydomain liquid crystal elastomers. Liquid crystal elastomers dramatically increase in stiffness by up to 90 % under low-amplitude, repetitive (dynamic) compression. By studying a systematic series of materials, we demonstrate that the stiffness increase is directly influenced by the liquid crystal content of the elastomers, the presence of a nematic liquid crystal phase and the use of a dynamic as opposed to static deformation. Through a combination of rheological measurements, polarizing optical microscopy and 2-D X-ray diffraction, we demonstrate that self-stiffening arises due to rotations of the nematic director in response to dynamic compression, and show that the behavior is consistent with the theory for nematic rubber elasticity. Previous work with liquid crystal elastomers has focused primarily on `soft elastic' deformations at large strains, but our findings indicate rich behavior at previously overlooked low-strain, dynamic deformations.

  8. Dynamic performance of dissipative dielectric elastomers under alternating mechanical load

    NASA Astrophysics Data System (ADS)

    Zhang, Junshi; Chen, Hualing; Sheng, Junjie; Liu, Lei; Wang, Yongquan; Jia, Shuhai

    2014-07-01

    This paper presents a theoretical study about the effect of dissipation on the dynamic performance of a dielectric elastomer membrane subject to a combination of mechanical load and voltage. The thermodynamic dissipative model is given and the equation of motion is deduced by a free energy method. It is found that when the applied mechanical load and voltage are static, the membrane may reach a state of equilibrium after the viscoelastic relaxation. When the voltage is static but the mechanical load is sinusoidal, the membrane will resonate at multiple frequencies. The study result indicates that the viscoelasticity can reduce the natural frequency and increase the mean stretch of the dielectric elastomer. After the power source is cut off, the effect of current leakage on dynamic performance under alternating mechanical load is that the natural frequency increases and the mean stretch reduces.

  9. Dynamic Reasoning under Probabilistic Uncertainty in the Semantic Web

    NASA Astrophysics Data System (ADS)

    Chen, Limin; Shi, Zhongzhi

    Towards a full realization of the Semantic Web as a source of processable information and services, we extend description logic ALCO@ to admit dynamic reasoning under probabilistic uncertainty. In our formalism, the crisp knowledge is encoded in DL-knowledgebase, and the uncertain one is in conditional constraints; atomic actions are represented in terms of their preconditions (conditional constraints) and effects (possibly negated ALCO@-assertions involving only atomic concepts). We also summarize some reasoning tasks in the new formalism and provide algorithms for them. This work is strictly related to the practical need of DL-based reasoning in the Semantic Web and is much closer than the prior formalisms to a practical formalism in the Web setting full of uncertain information and dynamic processing.

  10. Modeling the Underlying Dynamics of the Spread of Crime

    PubMed Central

    McMillon, David; Simon, Carl P.; Morenoff, Jeffrey

    2014-01-01

    The spread of crime is a complex, dynamic process that calls for a systems level approach. Here, we build and analyze a series of dynamical systems models of the spread of crime, imprisonment and recidivism, using only abstract transition parameters. To find the general patterns among these parameters—patterns that are independent of the underlying particulars—we compute analytic expressions for the equilibria and for the tipping points between high-crime and low-crime equilibria in these models. We use these expressions to examine, in particular, the effects of longer prison terms and of increased incarceration rates on the prevalence of crime, with a follow-up analysis on the effects of a Three-Strike Policy. PMID:24694545

  11. Stimulation of neuronal neurite outgrowth using functionalized carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Matsumoto, K.; Sato, C.; Naka, Y.; Whitby, R.; Shimizu, N.

    2010-03-01

    Low concentrations (0.11-1.7 µg ml - 1) of functionalized carbon nanotubes (CNTs), which are multi-walled CNTs modified by amino groups, when added with nerve growth factor (NGF), promoted outgrowth of neuronal neurites in dorsal root ganglion (DRG) neurons and rat pheochromocytoma cell line PC12h cells in culture media. The quantity of active extracellular signal-regulated kinase (ERK) was higher after the addition of both 0.85 µg ml - 1 CNTs and NGF than that with NGF alone. CNTs increased the number of cells with neurite outgrowth in DRG neurons and PC12h cells after the inhibition of the ERK signaling pathway using a mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor. Active ERK proteins were detected in MEK inhibitor-treated neurons after the addition of CNTs to the culture medium. These results demonstrate that CNTs may stimulate neurite outgrowth by activation of the ERK signaling pathway. Thus, CNTs are biocompatible and are promising candidates for biological applications and devices.

  12. Metastasis suppressor 1 regulates neurite outgrowth in primary neuron cultures.

    PubMed

    Yu, Juan; Lin, Shuyun; Wang, Mei; Liang, Lijun; Zou, Zijiao; Zhou, Xinfeng; Wang, Meichi; Chen, Ping; Wang, Ying

    2016-10-01

    Metastasis suppressor 1 (MTSS1) or missing in metastasis (MIM) is an actin- and membrane-binding protein with tumor suppressor functions. MTSS1 is important for cell morphology, motility, metastasis. The role of MTSS1 in cell morphology has been widely investigated in non-neuronal tissues; however the role of MTSS1 in neurite outgrowth remains unclear. Here we investigated the effect of MTSS1 on neurite outgrowth in primary cerebellar granule and hippocampal neurons of mouse. We found that overexpression of MTSS1 in cerebellar granule neurons significantly enhanced dendrite elaboration but inhibited axon elongation. This phenotype was significantly reduced by deletion of the Wiskott-Aldrich homology 2 (WH2) motif and point mutation in the insulin receptor substrate p53 (IRSp53) and MIM/MTSS1 homology (IMD) domain. Furthermore, inhibition of Rac1 activity or blocking of phosphatidyl inositol phosphates (PIPs) signaling decreased the effect of MTSS1 markedly. In accordance with the over-expression data, knockdown of MTSS1 in cerebellar granule neurons could increase the axon length but decrease the dendrite length and the number of dendrites. In addition, MTSS1 knock down in embryonic hippocampal neurons suppressed neurite branching and reduced dendrite length. Our findings have demonstrated that MTSS1 modulates neuronal morphology, possibly through a Rac1-PIPs signaling pathway. PMID:27401056

  13. Neurite outgrowth on fluorinated polyimide film micropatterned by ion irradiation

    NASA Astrophysics Data System (ADS)

    Okuyama, Y.; Sato, M.; Nagaoka, S.; Kawakami, H.; Suzuki, Y.; Iwaki, M.

    2003-05-01

    In this study, we investigated neurite outgrowth on a fluorinated polyimide film micropatterned by ion irradiation. We used the fluorinated polyimide because of its excellent thermal and mechanical properties and biocompatibility. Rattus norvegicus chromaphin (PC12) cells were used for in vitro studies. The polyimide films were irradiated with He +, Ne + or Kr + at 1 × 10 14 ions/cm 2 using an ion-beam mask. The lines in the mask were 120 and 160 μm wide and 120-160 μm apart. PC12 cells were selectively adhered on the polyimide film micropatterned by Kr +-irradiation. However, the neurite length on the film irradiated by Kr + was shorter than that determined in the film irradiated by He +. On the other hand, neurite outgrowth on the polyimide film micropatterned by He +-irradiation was at least 100 μm in length. This initial study indicated the enhanced outgrowth of PC12 cells on the fluorinated polyimide film micropatterned by ion irradiation.

  14. Stimulation of neurite outgrowth using positively charged hydrogels

    PubMed Central

    Dadsetan, Mahrokh; Knight, Andrew M.; Lu, Lichun; Windebank, Anthony J.; Yaszemski, Michael J.

    2009-01-01

    Autologous nerve grafts are currently the best option for the treatment of segmental peripheral nerve defects. However, autografts have several drawbacks including size mismatch and loss of sensation in the donor nerve’s sensory distribution. In this work, we have investigated the development of a synthetic hydrogel that contains positive charge for use as a substrate for nerve cell attachment and neurite outgrowth in culture. We have demonstrated that modification of oligo-(polyethylene glycol) fumarate (OPF) with a positively charged monomer improves primary sensory rat neuron attachment and differentiation in a dose-dependent manner. Positively charged hydrogels also supported attachment of dorsal root ganglion (DRG) explants that contain sensory neurons, Schwann cells and neuronal support cells. Furthermore, charged hydrogels were analyzed for the appearance of myelinated structures in a co-culture containing DRG neurons and Schwann cells. DRGs and Schwann cells remained viable on charged hydrogels for a time period of three weeks and neurites extended from the DRGs. Sudan black staining revealed that neurites emerging from DRGs were accompanied by migrating Schwann cells. These findings suggest that charged OPF hydrogels are capable of sustaining both primary nerve cells and the neural support cells that are critical for regeneration. PMID:19427689

  15. GIT1 enhances neurite outgrowth by stimulating microtubule assembly

    PubMed Central

    Li, Yi-sheng; Qin, Li-xia; Liu, Jie; Xia, Wei-liang; Li, Jian-ping; Shen, Hai-lian; Gao, Wei-Qiang

    2016-01-01

    GIT1, a G-protein-coupled receptor kinase interacting protein, has been reported to be involved in neurite outgrowth. However, the neurobiological functions of the protein remain unclear. In this study, we found that GIT1 was highly expressed in the nervous system, and its expression was maintained throughout all stages of neuritogenesis in the brain. In primary cultured mouse hippocampal neurons from GIT1 knockout mice, there was a significant reduction in total neurite length per neuron, as well as in the average length of axon-like structures, which could not be prevented by nerve growth factor treatment. Overexpression of GIT1 significantly promoted axon growth and fully rescued the axon outgrowth defect in the primary hippocampal neuron cultures from GIT1 knockout mice. The GIT1 N terminal region, including the ADP ribosylation factor-GTPase activating protein domain, the ankyrin domains and the Spa2 homology domain, were sufficient to enhance axonal extension. Importantly, GIT1 bound to many tubulin proteins and microtubule-associated proteins, and it accelerated microtubule assembly in vitro. Collectively, our findings suggest that GIT1 promotes neurite outgrowth, at least partially by stimulating microtubule assembly. This study provides new insight into the cellular and molecular pathogenesis of GIT1-associated neurological diseases. PMID:27127481

  16. Foxp2 Regulates Gene Networks Implicated in Neurite Outgrowth in the Developing Brain

    PubMed Central

    Vernes, Sonja C.; Oliver, Peter L.; Spiteri, Elizabeth; Lockstone, Helen E.; Puliyadi, Rathi; Taylor, Jennifer M.; Ho, Joses; Mombereau, Cedric; Brewer, Ariel; Lowy, Ernesto; Nicod, Jérôme; Groszer, Matthias; Baban, Dilair; Sahgal, Natasha; Cazier, Jean-Baptiste; Ragoussis, Jiannis; Davies, Kay E.; Geschwind, Daniel H.; Fisher, Simon E.

    2011-01-01

    Forkhead-box protein P2 is a transcription factor that has been associated with intriguing aspects of cognitive function in humans, non-human mammals, and song-learning birds. Heterozygous mutations of the human FOXP2 gene cause a monogenic speech and language disorder. Reduced functional dosage of the mouse version (Foxp2) causes deficient cortico-striatal synaptic plasticity and impairs motor-skill learning. Moreover, the songbird orthologue appears critically important for vocal learning. Across diverse vertebrate species, this well-conserved transcription factor is highly expressed in the developing and adult central nervous system. Very little is known about the mechanisms regulated by Foxp2 during brain development. We used an integrated functional genomics strategy to robustly define Foxp2-dependent pathways, both direct and indirect targets, in the embryonic brain. Specifically, we performed genome-wide in vivo ChIP–chip screens for Foxp2-binding and thereby identified a set of 264 high-confidence neural targets under strict, empirically derived significance thresholds. The findings, coupled to expression profiling and in situ hybridization of brain tissue from wild-type and mutant mouse embryos, strongly highlighted gene networks linked to neurite development. We followed up our genomics data with functional experiments, showing that Foxp2 impacts on neurite outgrowth in primary neurons and in neuronal cell models. Our data indicate that Foxp2 modulates neuronal network formation, by directly and indirectly regulating mRNAs involved in the development and plasticity of neuronal connections. PMID:21765815

  17. Fluid displacement under elastic membranes: Dynamics and interfacial instabilities

    NASA Astrophysics Data System (ADS)

    Al-Housseiny, Talal; Christov, Ivan; Juel, Anne; Stone, Howard

    2012-11-01

    The spreading of fluids under a flexible membrane is a feature of many systems such as the lateral intrusion of magma under a terrestrial crust, or when blood spreads underneath the skin giving the signature color of bruises. In this work, we investigate the displacement of a viscous fluid by a gas underneath an elastic membrane. We consider a radial Hele-Shaw cell where the upper plate is an elastic sheet. The dynamics of the interface between the injected gas and the displaced fluid are fundamentally modified by the presence of an elastic boundary, which leads to the suppression of viscous fingering below a critical flow rate. We demonstrate theoretically the mechanism of suppression and find the corresponding critical flow rate. In addition, we study the dynamics of a stable (circular) interface propagating underneath an elastic membrane and derive the scaling laws for both the position of the interface and the shape of the elastic membrane. Our theoretical findings agree very well with the experimental results of D. Pihler-Puzovic et al. (PRL 2012). T. T. Al-Housseiny is supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-0646086.

  18. Electromechanical fatigue in IPMC under dynamic energy harvesting conditions

    NASA Astrophysics Data System (ADS)

    Krishnaswamy, Arvind; Roy Mahapatra, D.

    2011-04-01

    Ionic polymer-metal composites (IPMCs) are an interesting subset of smart, multi-functional materials that have shown promises in energy conversion technologies. Being electromechanically coupled, IPMCs can function as dynamic actuators and sensors, transducers for energy conversion and harvesting, as well as artificial muscles for medical and industrial applications. Like all natural materials, even IPMCs undergo fatigue under dynamic load conditions. Here, we investigate the electromechanical fatigue induced in the IPMCs due to the application of cyclic mechanical bending deformation under hydrodynamic energy harvesting condition. Considering the viscoelastic nature of the IPMC, we employ an analytical approach to modeling electromechanical fatigue primarily under the cyclic stresses induced in the membrane. The polymer-metal composite undergoes cyclic softening throughout the fatigue life without attaining a saturated state of charge migration. However, it results in (1) degradation of electromechanical performance; (2) nucleation and growth of microscopic cracks in the metal electrodes; (3) delamination of metal electrodes at the polymer-electrode interface. To understand these processes, we employ a phenomenological approach based on experimentally measured relaxation properties of the IPMC membrane. Electromechanical performance improves significantly with self-healing like properties for a certain range of relaxation time. This is due to reorientation of the backbone polymer chains which eventually leads to a regenerative process with increased charge transport.

  19. Marginally subcritical dynamics explain enhanced stimulus discriminability under attention

    PubMed Central

    Tomen, Nergis; Rotermund, David; Ernst, Udo

    2014-01-01

    Recent experimental and theoretical work has established the hypothesis that cortical neurons operate close to a critical state which describes a phase transition from chaotic to ordered dynamics. Critical dynamics are suggested to optimize several aspects of neuronal information processing. However, although critical dynamics have been demonstrated in recordings of spontaneously active cortical neurons, little is known about how these dynamics are affected by task-dependent changes in neuronal activity when the cortex is engaged in stimulus processing. Here we explore this question in the context of cortical information processing modulated by selective visual attention. In particular, we focus on recent findings that local field potentials (LFPs) in macaque area V4 demonstrate an increase in γ-band synchrony and a simultaneous enhancement of object representation with attention. We reproduce these results using a model of integrate-and-fire neurons where attention increases synchrony by enhancing the efficacy of recurrent interactions. In the phase space spanned by excitatory and inhibitory coupling strengths, we identify critical points and regions of enhanced discriminability. Furthermore, we quantify encoding capacity using information entropy. We find a rapid enhancement of stimulus discriminability with the emergence of synchrony in the network. Strikingly, only a narrow region in the phase space, at the transition from subcritical to supercritical dynamics, supports the experimentally observed discriminability increase. At the supercritical border of this transition region, information entropy decreases drastically as synchrony sets in. At the subcritical border, entropy is maximized under the assumption of a coarse observation scale. Our results suggest that cortical networks operate at such near-critical states, allowing minimal attentional modulations of network excitability to substantially augment stimulus representation in the LFPs. PMID:25202240

  20. Dynamics of lysozyme and its hydration water under electric field

    SciTech Connect

    Favi, Pelagie M; Zhang, Qiu; O'Neill, Hugh Michael; Mamontov, Eugene; Omar Diallo, Souleymane; Palmer, Jeremy

    2014-01-01

    The effects of static electric field on the dynamics of lysozyme and its hydration water have been investigated by means of incoherent quasi-elastic neutron scattering (QENS). Measurements were performed on lysozyme samples, hydrated respectively with heavy water (D2O) to capture the protein dynamics, and with light water (H2O), to probe the dynamics of the hydration shell, in the temperature range from 210 < T < 260 K. The hydration fraction in both cases was about 0.38 gram of water per gram of dry protein. The field strengths investigated were respectively 0 kV/mm and 2 kV/mm ( 2 106 V/m) for the protein hydrated with D2O and 0 kV and 1 kV/mm for the H2O-hydrated counterpart. While the overall internal protons dynamics of the protein appears to be unaffected by the application of electric field up to 2 kV/mm, likely due to the stronger intra-molecular interactions, there is also no appreciable quantitative enhancement of the diffusive dynamics of the hydration water, as would be anticipated based on our recent observations in water confined in silica pores under field values of 2.5 kV/mm. This may be due to the difference in surface interactions between water and the two adsorption hosts (silica and protein), or to the existence of a critical threshold field value Ec 2 3 kV/mm for increased molecular diffusion, for which electrical breakdown is a limitation for our sample.

  1. Wave packet dynamics under effect of a pulsed electric field

    NASA Astrophysics Data System (ADS)

    da Silva, A. R. C. B.; de Moura, F. A. B. F.; Dias, W. S.

    2016-06-01

    We studied the dynamics of an electron in a crystalline one-dimensional model under effect of a time-dependent Gaussian field. The time evolution of an initially Gaussian wave packet it was obtained through the numerical solution of the time-dependent Schrödinger equation. Our analysis consists of computing the electronic centroid as well as the mean square displacement. We observe that the electrical pulse is able to promote a special kind of displacement along the chain. We demonstrated a direct relation between the group velocity of the wave packet and the applied electrical pulses. We compare those numerical calculations with a semi-classical approach.

  2. Barothropic relaxing media under pressure perturbations: Nonlinear dynamics

    NASA Astrophysics Data System (ADS)

    Kuetche, Victor K.

    2015-12-01

    In this paper, we delve into the dynamics of a barothropic relaxing medium under pressure perturbations originating from blast wave explosions in the milieu. Analyzing the problem within the viewpoint of the Lyakhov formalism of geodynamic systems, we derive a complex-valued nonlinear evolution equation which models the wave propagation of the pressure perturbations within the barothropic medium. As a result, we find that the previous system can be circularly polarized and hence support traveling rotating pressure excitations which profiles strongly depend upon their angular momenta. In the wake of these results, we address some physical implications of the findings alongside their potential applications.

  3. Dynamics of propagating front into sand ripples under regular waves.

    PubMed

    Lebunetel-Levaslot, J; Jarno-Druaux, A; Ezersky, A B; Marin, F

    2010-09-01

    The results of an experimental study of pattern formation on sandy bottom under the action of regular harmonic surface waves are reported. It is found that two modes of pattern formation occur: sand ripples form uniformly on the whole bottom or from localized nucleation sites. In the second regime, the ripples appear in isolated regions (patches) increasing in size, and front propagation speed is measured. A simple dynamical model based on the Ginzburg-Landau equation is proposed to explain the characteristics of patches. PMID:21230122

  4. Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons.

    PubMed

    Murayama, Chiaki; Watanabe, Shimpei; Nakamura, Motokazu; Norimoto, Hisayoshi

    2015-01-01

    Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine) is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH), a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF) in cultured rat dorsal root ganglion (DRG) neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control), a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in "itch-scratch" animal models is under investigation. PMID:26287150

  5. Dynamic Myofibrillar Remodeling in Live Cardiomyocytes under Static Stretch

    PubMed Central

    Yang, Huaxiao; Schmidt, Lucas P.; Wang, Zhonghai; Yang, Xiaoqi; Shao, Yonghong; Borg, Thomas K.; Markwald, Roger; Runyan, Raymond; Gao, Bruce Z.

    2016-01-01

    An increase in mechanical load in the heart causes cardiac hypertrophy, either physiologically (heart development, exercise and pregnancy) or pathologically (high blood pressure and heart-valve regurgitation). Understanding cardiac hypertrophy is critical to comprehending the mechanisms of heart development and treatment of heart disease. However, the major molecular event that occurs during physiological or pathological hypertrophy is the dynamic process of sarcomeric addition, and it has not been observed. In this study, a custom-built second harmonic generation (SHG) confocal microscope was used to study dynamic sarcomeric addition in single neonatal CMs in a 3D culture system under acute, uniaxial, static, sustained stretch. Here we report, for the first time, live-cell observations of various modes of dynamic sarcomeric addition (and how these real-time images compare to static images from hypertrophic hearts reported in the literature): 1) Insertion in the mid-region or addition at the end of a myofibril; 2) Sequential addition with an existing myofibril as a template; and 3) Longitudinal splitting of an existing myofibril. The 3D cell culture system developed on a deformable substrate affixed to a stretcher and the SHG live-cell imaging technique are unique tools for real-time analysis of cultured models of hypertrophy. PMID:26861590

  6. Stock price dynamics and option valuations under volatility feedback effect

    NASA Astrophysics Data System (ADS)

    Kanniainen, Juho; Piché, Robert

    2013-02-01

    According to the volatility feedback effect, an unexpected increase in squared volatility leads to an immediate decline in the price-dividend ratio. In this paper, we consider the properties of stock price dynamics and option valuations under the volatility feedback effect by modeling the joint dynamics of stock price, dividends, and volatility in continuous time. Most importantly, our model predicts the negative effect of an increase in squared return volatility on the value of deep-in-the-money call options and, furthermore, attempts to explain the volatility puzzle. We theoretically demonstrate a mechanism by which the market price of diffusion return risk, or an equity risk-premium, affects option prices and empirically illustrate how to identify that mechanism using forward-looking information on option contracts. Our theoretical and empirical results support the relevance of the volatility feedback effect. Overall, the results indicate that the prevailing practice of ignoring the time-varying dividend yield in option pricing can lead to oversimplification of the stock market dynamics.

  7. Dynamic Myofibrillar Remodeling in Live Cardiomyocytes under Static Stretch.

    PubMed

    Yang, Huaxiao; Schmidt, Lucas P; Wang, Zhonghai; Yang, Xiaoqi; Shao, Yonghong; Borg, Thomas K; Markwald, Roger; Runyan, Raymond; Gao, Bruce Z

    2016-01-01

    An increase in mechanical load in the heart causes cardiac hypertrophy, either physiologically (heart development, exercise and pregnancy) or pathologically (high blood pressure and heart-valve regurgitation). Understanding cardiac hypertrophy is critical to comprehending the mechanisms of heart development and treatment of heart disease. However, the major molecular event that occurs during physiological or pathological hypertrophy is the dynamic process of sarcomeric addition, and it has not been observed. In this study, a custom-built second harmonic generation (SHG) confocal microscope was used to study dynamic sarcomeric addition in single neonatal CMs in a 3D culture system under acute, uniaxial, static, sustained stretch. Here we report, for the first time, live-cell observations of various modes of dynamic sarcomeric addition (and how these real-time images compare to static images from hypertrophic hearts reported in the literature): 1) Insertion in the mid-region or addition at the end of a myofibril; 2) Sequential addition with an existing myofibril as a template; and 3) Longitudinal splitting of an existing myofibril. The 3D cell culture system developed on a deformable substrate affixed to a stretcher and the SHG live-cell imaging technique are unique tools for real-time analysis of cultured models of hypertrophy. PMID:26861590

  8. Simulating spin dynamics in organic solids under heteronuclear decoupling.

    PubMed

    Frantsuzov, Ilya; Ernst, Matthias; Brown, Steven P; Hodgkinson, Paul

    2015-09-01

    Although considerable progress has been made in simulating the dynamics of multiple coupled nuclear spins, predicting the evolution of nuclear magnetisation in the presence of radio-frequency decoupling remains challenging. We use exact numerical simulations of the spin dynamics under simultaneous magic-angle spinning and RF decoupling to determine the extent to which numerical simulations can be used to predict the experimental performance of heteronuclear decoupling for the CW, TPPM and XiX sequences, using the methylene group of glycine as a model system. The signal decay times are shown to be strongly dependent on the largest spin order simulated. Unexpectedly large differences are observed between the dynamics with and without spin echoes. Qualitative trends are well reproduced by modestly sized spin system simulations, and the effects of finite spin-system size can, in favourable cases, be mitigated by extrapolation. Quantitative prediction of the behaviour in complex parameter spaces is found, however, to be very challenging, suggesting that there are significant limits to the role of numerical simulations in RF decoupling problems, even when specialist techniques, such as state-space restriction, are used. PMID:26073419

  9. Dynamics of dendritic polymers in the bulk and under confinement

    SciTech Connect

    Chrissopoulou, K.; Fotiadou, S.; Androulaki, K.; Anastasiadis, S. H.; Tanis, I.; Karatasos, K.; Prevosto, D.; Labardi, M.; Frick, B.

    2014-05-15

    The structure and dynamics of a hyperbranched polyesteramide (Hybrane® S 1200) polymer and its nanocomposites with natural montmorillonite (Na{sup +}-MMT) are investigated by XRD, DSC, QENS, DS and Molecular Dynamics (MD) simulation. In bulk, the energy-resolved elastically scattered intensity from the polymer exhibits two relaxation steps, one attributed to sub-T{sub g} motions and one observed at temperatures above the glass transition, T{sub g}. The QENS spectra measured over the complete temperature range are consistent with the elastic measurements and can be correlated to the results emerging from the detailed description afforded by the atomistic simulations, which predict the existence of three relaxation processes. Moreover, dielectric spectroscopy shows the sub- T{sub g} beta process as well as the segmental relaxation. For the nanocomposites, XRD reveals an intercalated structure for all hybrids with distinct interlayer distances due to polymer chains residing within the galleries of the Na{sup +}-MMT. The polymer chains confined within the galleries show similarities in the behavior with that of the polymer in the bulk for temperatures below the bulk polymer T{sub g}, whereas they exhibit frozen dynamics under confinement at temperatures higher than that.

  10. Deterministic nature of the underlying dynamics of surface wind fluctuations

    NASA Astrophysics Data System (ADS)

    Sreelekshmi, R. C.; Asokan, K.; Satheesh Kumar, K.

    2012-10-01

    Modelling the fluctuations of the Earth's surface wind has a significant role in understanding the dynamics of atmosphere besides its impact on various fields ranging from agriculture to structural engineering. Most of the studies on the modelling and prediction of wind speed and power reported in the literature are based on statistical methods or the probabilistic distribution of the wind speed data. In this paper we investigate the suitability of a deterministic model to represent the wind speed fluctuations by employing tools of nonlinear dynamics. We have carried out a detailed nonlinear time series analysis of the daily mean wind speed data measured at Thiruvananthapuram (8.483° N,76.950° E) from 2000 to 2010. The results of the analysis strongly suggest that the underlying dynamics is deterministic, low-dimensional and chaotic suggesting the possibility of accurate short-term prediction. As most of the chaotic systems are confined to laboratories, this is another example of a naturally occurring time series showing chaotic behaviour.

  11. HAWT dynamic stall response asymmetries under yawed flow conditions

    NASA Astrophysics Data System (ADS)

    Schreck, S.; Robinson, M.; Hand, M.; Simms, D.

    2000-10-01

    Horizontal axis wind turbines can experience significant time-varying aerodynamic loads, potentially causing adverse effects on structures, mechanical components and power production. As designers attempt lighter and more flexible wind energy machines, greater accuracy and robustness will become even more critical in future aerodynamics models. Aerodynamics modelling advances, in turn, will rely on more thorough comprehension of the three-dimensional, unsteady, vortical flows that dominate wind turbine blade aerodynamics under high-load conditions. To experimentally characterize these flows, turbine blade surface pressures were acquired at multiple span locations via the NREL Phase IV Unsteady Aerodynamics Experiment. Surface pressures and associated normal force histories were used to characterize dynamic stall vortex kinematics and normal force amplification. Dynamic stall vortices and normal force amplification were confirmed to occur in response to angle-of-attack excursions above the static stall threshold. Stall vortices occupied approximately one-half of the blade span and persisted for nearly one-fourth of the blade rotation cycle. Stall vortex convection varied along the blade, resulting in dramatic deformation of the vortex. Presence and deformation of the dynamic stall vortex produced corresponding amplification of normal forces. Analyses revealed consistent alterations to vortex kinematics in response to changes in reduced frequency, span location and yaw error. Finally, vortex structures and kinematics not previously documented for wind turbine blades were isolated. Published in 2000 by John Wiley & Sons, Ltd.

  12. Dynamic properties of elastomer cartridge specimens under a rotating load

    NASA Technical Reports Server (NTRS)

    Darlow, M. S.; Smalley, A. J.; Cunningham, R. E.

    1979-01-01

    This paper presents the results of a program of analysis and test to determine the dynamic properties of elastomer cartridges operating under a rotating load. These measured properties were compared to predictions based on results of unidirectional tests with the same elastomer material. The test method for the dynamic stiffness and damping measurements was essentially the same as the Base Excitation Resonant Mass Method. The primary difference is that the exciting force used for these most recent tests was exerted by rotating unbalance in a rotational test rig rather than a shake table. The specimens tested were: two rectangular cross-section, continuous ring cartridges of different cross-section and three cylindrical button cartridges of different button thickness. Tests were performed for strains from about 0.0001 to about 0.01 (double amplitude). Material properties and prediction equations determined from reciprocating tests were used to make numerical predictions of stiffness, damping, and loss coefficient for the test elements, with encouraging results. Strain was shown to be an important parameter in determining these dynamic properties, particularly damping and loss coefficient.

  13. Dynamics of a polyelectrolyte under a constant electric field

    NASA Astrophysics Data System (ADS)

    Park, Pyeong Jun

    2015-11-01

    We perform a molecular dynamics simulation of a polyelectrolyte in a viscous fluid under an external electric field to study the dynamics of gel-free electrophoresis. To incorporate the hydrodynamic effects, we employ a coarse-grained description of water by using multiparticle collision dynamics. We use a screened Coulomb interaction among the monomers and explicit monovalent counterions to model the electrostatic interactions in an ionic solution. The mobility of the polyelectrolyte µ is obtained as a function of the molecular weight N, the electric field strength E,and the Debye screening length of the solvent λ. The mobility is found to be independent of N for large N and to exhibit a maximum at a certain N for a large λ, which are in agreement with experimental results. The dependence of µ on E is also examined and discussed by considering the effects of an electric field on counterion condensation. The dependence of µ on λ shows a discrepancy between our simulation and experiments, which implies that the added salts not only screen out the Coulomb interaction but also participate in the counterion condensation significantly.

  14. Rupture of a biomembrane under dynamic surface tension

    NASA Astrophysics Data System (ADS)

    Bicout, D. J.; Kats, E.

    2012-03-01

    How long will a fluid membrane vesicle stressed with a steady ramp of micropipette last before rupture? Or conversely, how high should the surface tension be to rupture such a membrane? To answer these challenging questions we developed a theoretical framework that allows for the description and reproduction of dynamic tension spectroscopy (DTS) observations. The kinetics of the membrane rupture under ramps of surface tension is described as a succession of an initial pore formation followed by the Brownian process of the pore radius crossing the time-dependent energy barrier. We present the formalism and a derive (formal) analytical expression of the survival probability describing the fate of the membrane under DTS conditions. Using numerical simulations for the membrane prepared in an initial state with a given distribution of times for pore nucleation, we study the membrane lifetime (or inverse of rupture rate) and distribution of membrane surface tension at rupture as a function of membrane characteristics like pore nucleation rate, the energy barrier to failure, and tension loading rate. It is found that simulations reproduce the main features of DTS experiments, particularly the pore nucleation and pore-size diffusion-controlled limits of membrane rupture dynamics. This approach can be adapted and applied to processes of permeation and pore opening in membranes (electroporation, membrane disruption by antimicrobial peptides, vesicle fusion).

  15. Three dimensional dynamics of rotating structures under mixed boundary conditions

    NASA Astrophysics Data System (ADS)

    Bediz, Bekir; Romero, L. A.; Ozdoganlar, O. Burak

    2015-12-01

    This paper presents the spectral-Tchebychev (ST) technique for solution of three dimensional (3D) dynamics of rotating structures. In particular, structures that exhibit coupled dynamic response require a 3D modeling approach to capture their dynamic behavior. Rotational motions further complicate this behavior, inducing coriolis, centrifugal softening, and (nonlinear) stress-stiffening effects. Therefore, a 3D solution approach is needed to accurately capture the rotational dynamics. The presented 3D-ST technique provides a fast-converging and precise solution approach for rotational dynamics of structures with complex geometries and mixed boundary conditions. Specifically, unlike finite elements techniques, the presented technique uses a series expansion approach considering distributed-parameter system equations: The integral boundary value problem for rotating structures is discretized using the spectral-Tchebychev approach. To simplify the domain of the structures, cross-sectional and rotational transformations are applied to problems with curved cross-section and pretwisted geometry. The nonlinear terms included in the integral boundary value problem are linearized around an equilibrium solution using the quasi-static method. As a result, mass, damping, and stiffness matrices, as well as a forcing vector, are obtained for a given rotating structure. Several case studies are then performed to demonstrate the application and effectiveness of the 3D-ST solution. For each problem, the natural frequencies and modes shapes from the 3D-ST solution are compared to those from the literature (when available) and to those from a commercial finite elements software. The case studies include rotating/spinning parallelepipeds under free and mixed boundary conditions, and a cantilevered pretwisted beam (i.e., rotating blade) with an airfoil geometry rotating on a hub. It is seen that the natural frequencies and mode shapes from the 3D-ST technique differ from those from the

  16. Human Umbilical Tissue-Derived Cells Promote Synapse Formation and Neurite Outgrowth via Thrombospondin Family Proteins

    PubMed Central

    Koh, Sehwon; Kim, Namsoo; Yin, Henry H.; Harris, Ian R.; Dejneka, Nadine S.

    2015-01-01

    Cell therapy demonstrates great potential for the treatment of neurological disorders. Human umbilical tissue-derived cells (hUTCs) were previously shown to have protective and regenerative effects in animal models of stroke and retinal degeneration, but the underlying therapeutic mechanisms are unknown. Because synaptic dysfunction, synapse loss, degeneration of neuronal processes, and neuronal death are hallmarks of neurological diseases and retinal degenerations, we tested whether hUTCs contribute to tissue repair and regeneration by stimulating synapse formation, neurite outgrowth, and neuronal survival. To do so, we used a purified rat retinal ganglion cell culture system and found that hUTCs secrete factors that strongly promote excitatory synaptic connectivity and enhance neuronal survival. Additionally, we demonstrated that hUTCs support neurite outgrowth under normal culture conditions and in the presence of the growth-inhibitory proteins chondroitin sulfate proteoglycan, myelin basic protein, or Nogo-A (reticulon 4). Furthermore, through biochemical fractionation and pharmacology, we identified the major hUTC-secreted synaptogenic factors as the thrombospondin family proteins (TSPs), TSP1, TSP2, and TSP4. Silencing TSP expression in hUTCs, using small RNA interference, eliminated both the synaptogenic function of these cells and their ability to promote neurite outgrowth. However, the majority of the prosurvival functions of hUTC-conditioned media was spared after TSP knockdown, indicating that hUTCs secrete additional neurotrophic factors. Together, our findings demonstrate that hUTCs affect multiple aspects of neuronal health and connectivity through secreted factors, and each of these paracrine effects may individually contribute to the therapeutic function of these cells. SIGNIFICANCE STATEMENT Human umbilical tissue-derived cells (hUTC) are currently under clinical investigation for the treatment of geographic atrophy secondary to age-related macular

  17. Molecular dynamics simulations of membrane proteins under asymmetric ionic concentrations

    PubMed Central

    Khalili-Araghi, Fatemeh; Ziervogel, Brigitte; Gumbart, James C.

    2013-01-01

    A computational method is developed to allow molecular dynamics simulations of biomembrane systems under realistic ionic gradients and asymmetric salt concentrations while maintaining the conventional periodic boundary conditions required to minimize finite-size effects in an all-atom explicit solvent representation. The method, which consists of introducing a nonperiodic energy step acting on the ionic species at the edge of the simulation cell, is first tested with illustrative applications to a simple membrane slab model and a phospholipid membrane bilayer. The nonperiodic energy-step method is then used to calculate the reversal potential of the bacterial porin OmpF, a large cation-specific β-barrel channel, by simulating the I-V curve under an asymmetric 10:1 KCl concentration gradient. The calculated reversal potential of 28.6 mV is found to be in excellent agreement with the values of 26–27 mV measured from lipid bilayer experiments, thereby demonstrating that the method allows realistic simulations of nonequilibrium membrane transport with quantitative accuracy. As a final example, the pore domain of Kv1.2, a highly selective voltage-activated K+ channel, is simulated in a lipid bilayer under conditions that recreate, for the first time, the physiological K+ and Na+ concentration gradients and the electrostatic potential difference of living cells. PMID:24081985

  18. Material dynamics under extreme conditions of pressure and strain rate

    SciTech Connect

    Remington, B A; Allen, P; Bringa, E; Hawreliak, J; Ho, D; Lorenz, K T; Lorenzana, H; Meyers, M A; Pollaine, S W; Rosolankova, K; Sadik, B; Schneider, M S; Swift, D; Wark, J; Yaakobi, B

    2005-09-06

    Solid state experiments at extreme pressures (10-100 GPa) and strain rates ({approx}10{sup 6}-10{sup 8}s{sup -1}) are being developed on high-energy laser facilities, and offer the possibility for exploring new regimes of materials science. These extreme solid-state conditions can be accessed with either shock loading or with a quasi-isentropic ramped pressure drive. Velocity interferometer measurements establish the high pressure conditions. Constitutive models for solid-state strength under these conditions are tested by comparing 2D continuum simulations with experiments measuring perturbation growth due to the Rayleigh-Taylor instability in solid-state samples. Lattice compression, phase, and temperature are deduced from extended x-ray absorption fine structure (EXAFS) measurements, from which the shock-induced {alpha}-{omega} phase transition in Ti and the {alpha}-{var_epsilon} phase transition in Fe are inferred to occur on sub-nanosec time scales. Time resolved lattice response and phase can also be measured with dynamic x-ray diffraction measurements, where the elastic-plastic (1D-3D) lattice relaxation in shocked Cu is shown to occur promptly (< 1 ns). Subsequent large-scale molecular dynamics (MD) simulations elucidate the microscopic dynamics that underlie the 3D lattice relaxation. Deformation mechanisms are identified by examining the residual microstructure in recovered samples. The slip-twinning threshold in single-crystal Cu shocked along the [001] direction is shown to occur at shock strengths of {approx}20 GPa, whereas the corresponding transition for Cu shocked along the [134] direction occurs at higher shock strengths. This slip-twinning threshold also depends on the stacking fault energy (SFE), being lower for low SFE materials. Designs have been developed for achieving much higher pressures, P > 1000 GPa, in the solid state on the National Ignition Facility (NIF) laser.

  19. A technique for measuring dynamic friction coefficient under impact loading

    NASA Astrophysics Data System (ADS)

    Lin, Y. L.; Qin, J. G.; Chen, R.; Zhao, P. D.; Lu, F. Y.

    2014-09-01

    We develop a novel setup based on the split Hopkinson pressure bar technique to test the dynamic friction coefficient under impact loading. In the setup, the major improvement is that the end of the incident bar near the specimen is wedge-shaped, which results in a combined compressive and shear loading applied to the specimen. In fact, the shear loading is caused by the interfacial friction between specimen and bars. Therefore, when the two loading force histories are measured, the friction coefficient histories can be calculated without any assumptions and theoretical derivations. The geometry of the friction pairs is simple, and can be either cuboid or cylindrical. Regarding the measurements, two quartz transducers are used to directly record the force histories, and an optical apparatus is designed to test the interfacial slip movement. By using the setup, the dynamic friction coefficient of PTFE/aluminum 7075 friction pairs was tested. The time resolved dynamic friction coefficient and slip movement histories were achieved. The results show that the friction coefficient changes during the loading process, the average data of the relatively stable flat plateau section of the friction coefficient curves is 0.137, the maximum normal pressure is 52 MPa, the maximum relative slip velocity is 1.5 m/s, and the acceleration is 8400 m2/s. Furthermore, the friction test was simulated using an explicit FEM code LS-DYNA. The simulation results showed that the constant pressure and slip velocity can both be obtained with a wide flat plateau incident pulse. For some special friction pairs, normal pressure up to a few hundred MPa, interfacial slip velocities up to 10 m/s, and slip movement up to centimeter-level can be expected.

  20. A technique for measuring dynamic friction coefficient under impact loading.

    PubMed

    Lin, Y L; Qin, J G; Chen, R; Zhao, P D; Lu, F Y

    2014-09-01

    We develop a novel setup based on the split Hopkinson pressure bar technique to test the dynamic friction coefficient under impact loading. In the setup, the major improvement is that the end of the incident bar near the specimen is wedge-shaped, which results in a combined compressive and shear loading applied to the specimen. In fact, the shear loading is caused by the interfacial friction between specimen and bars. Therefore, when the two loading force histories are measured, the friction coefficient histories can be calculated without any assumptions and theoretical derivations. The geometry of the friction pairs is simple, and can be either cuboid or cylindrical. Regarding the measurements, two quartz transducers are used to directly record the force histories, and an optical apparatus is designed to test the interfacial slip movement. By using the setup, the dynamic friction coefficient of PTFE/aluminum 7075 friction pairs was tested. The time resolved dynamic friction coefficient and slip movement histories were achieved. The results show that the friction coefficient changes during the loading process, the average data of the relatively stable flat plateau section of the friction coefficient curves is 0.137, the maximum normal pressure is 52 MPa, the maximum relative slip velocity is 1.5 m/s, and the acceleration is 8400 m(2)/s. Furthermore, the friction test was simulated using an explicit FEM code LS-DYNA. The simulation results showed that the constant pressure and slip velocity can both be obtained with a wide flat plateau incident pulse. For some special friction pairs, normal pressure up to a few hundred MPa, interfacial slip velocities up to 10 m/s, and slip movement up to centimeter-level can be expected. PMID:25273746

  1. The dynamic behaviour of postbuckled composite plates under acoustic excitation

    NASA Technical Reports Server (NTRS)

    Ng, C. F.; White, R. G.

    1988-01-01

    The Rayleigh-Ritz method was used to find the postbuckling static displacement pattern of a composite plane (CFRP) under uniaxial in-plane compression of uniform edge-shortening. The resonance frequencies and mode shapes at various postbuckled states are then evaluated by eigenvalue analysis of the dynamical matrix equation consisting of up-dated tangential stiffness matrix at corresponding static configuration. The theoretical results are compared with experimental results obtained in 16-layered CFRP laminate of aspect ratio 1.5. The resonance frequencies and mode shapes obtained are used to interpret the multimodal and nonlinear strain responses to high level of acoustic excitation. The dominance of second-mode contribution and softening-spring behavior are found in the strain response of postbuckled plates.

  2. Dynamic properties of structural transition in iron under uniaxial compression.

    PubMed

    Shao, J L; Duan, S Q; He, A M; Qin, C S; Wang, P

    2009-06-17

    By using molecular dynamics simulations, we have successfully simulated the bcc [Formula: see text] hcp structural transition in single-crystal iron under isothermal compression along the [001] direction. The results reveal a distinct softening of C(33) and a hardening of C(31) (or C(32)) prior to the transition and an over-relaxation of the stress after transition. Above the critical stress the morphology evolution of structural transition is analyzed, which can be divided into four stages: hcp homogeneously nucleated, columnar grains formed, nuclei competed and merged, and a laminar structure formed along {110} planes. Besides, our simulations demonstrate that in mixed phases the hcp phase has negative shear stress and the potential of the hcp phase is higher than the bcc phase, and the shear stress of the system keeps a linear decrease with hcp mass fraction. The effect of temperature on the structural transition is also discussed. PMID:21693955

  3. Dynamic Group Diffie-Hellman Key Exchange under standard assumptions

    SciTech Connect

    Bresson, Emmanuel; Chevassut, Olivier; Pointcheval, David

    2002-02-14

    Authenticated Diffie-Hellman key exchange allows two principals communicating over a public network, and each holding public-private keys, to agree on a shared secret value. In this paper we study the natural extension of this cryptographic problem to a group of principals. We begin from existing formal security models and refine them to incorporate major missing details (e.g., strong-corruption and concurrent sessions). Within this model we define the execution of a protocol for authenticated dynamic group Diffie-Hellman and show that it is provably secure under the decisional Diffie-Hellman assumption. Our security result holds in the standard model and thus provides better security guarantees than previously published results in the random oracle model.

  4. Effect of Testosterone on Neuronal Morphology and Neuritic Growth of Fetal Lamb Hypothalamus-Preoptic Area and Cerebral Cortex in Primary Culture.

    PubMed

    Reddy, Radhika C; Amodei, Rebecka; Estill, Charles T; Stormshak, Fred; Meaker, Mary; Roselli, Charles E

    2015-01-01

    Testosterone plays an essential role in sexual differentiation of the male sheep brain. The ovine sexually dimorphic nucleus (oSDN), is 2 to 3 times larger in males than in females, and this sex difference is under the control of testosterone. The effect of testosterone on oSDN volume may result from enhanced expansion of soma areas and/or dendritic fields. To test this hypothesis, cells derived from the hypothalamus-preoptic area (HPOA) and cerebral cortex (CTX) of lamb fetuses were grown in primary culture to examine the direct morphological effects of testosterone on these cellular components. We found that within two days of plating, neurons derived from both the HPOA and CTX extend neuritic processes and express androgen receptors and aromatase immunoreactivity. Both treated and control neurites continue to grow and branch with increasing time in culture. Treatment with testosterone (10 nM) for 3 days significantly (P < 0.05) increased both total neurite outgrowth (35%) and soma size (8%) in the HPOA and outgrowth (21%) and number of branch points (33%) in the CTX. These findings indicate that testosterone-induced somal enlargement and neurite outgrowth in fetal lamb neurons may contribute to the development of a fully masculine sheep brain. PMID:26053052

  5. Dynamic response of a riser under excitation of internal waves

    NASA Astrophysics Data System (ADS)

    Lou, Min; Yu, Chenglong; Chen, Peng

    2015-12-01

    In this paper, the dynamic response of a marine riser under excitation of internal waves is studied. With the linear approximation, the governing equation of internal waves is given. Based on the rigid-lid boundary condition assumption, the equation is solved by Thompson-Haskell method. Thus the velocity field of internal waves is obtained by the continuity equation. Combined with the modified Morison formula, using finite element method, the motion equation of riser is solved in time domain with Newmark-β method. The computation programs are compiled to solve the differential equations in time domain. Then we get the numerical results, including riser displacement and transfiguration. It is observed that the internal wave will result in circular shear flow, and the first two modes have a dominant effect on dynamic response of the marine riser. In the high mode, the response diminishes rapidly. In different modes of internal waves, the deformation of riser has different shapes, and the location of maximum displacement shifts. Studies on wave parameters indicate that the wave amplitude plays a considerable role in response displacement of riser, while the wave frequency contributes little. Nevertheless, the internal waves of high wave frequency will lead to a high-frequency oscillation of riser; it possibly gives rise to fatigue crack extension and partial fatigue failure.

  6. Void collapse under distributed dynamic loading near material interfaces

    NASA Astrophysics Data System (ADS)

    Shpuntova, Galina; Austin, Joanna

    2012-11-01

    Collapsing voids cause significant damage in diverse applications from biomedicine to underwater propulsion to explosives. While shock-induced void collapse has been studied extensively, less attention has been devoted to stress wave loading, which will occur instead if there are mechanisms for wave attenuation or if the impact velocity is relatively low. A set of dynamic experiments was carried out in a model experimental setup to investigate the effect of acoustic heterogeneities in the surrounding medium on void collapse. Two tissue-surrogate polymer materials of varying acoustic properties were used to create flowfield geometries involving a boundary and a void. A stress wave, generated by projectile impact, triggered void collapse in the gelatinous polymer medium. When the length scales of features in the flow field were on the same order of magnitude as the stress wave length scale, the presence of the boundary was found to affect the void collapse process relative to collapse in the absence of a boundary. This effect was quantified for a range of geometries and impact conditions using a two-color, single-frame particle image velocimetry technique. Research supported by NSF Award #0954769, ``CAREER: Dynamics and damage of void collapse in biological materials under stress wave loading'' with Prof. Henning Winter as Program Manager.

  7. Sustainable infrastructure system modeling under uncertainties and dynamics

    NASA Astrophysics Data System (ADS)

    Huang, Yongxi

    Infrastructure systems support human activities in transportation, communication, water use, and energy supply. The dissertation research focuses on critical transportation infrastructure and renewable energy infrastructure systems. The goal of the research efforts is to improve the sustainability of the infrastructure systems, with an emphasis on economic viability, system reliability and robustness, and environmental impacts. The research efforts in critical transportation infrastructure concern the development of strategic robust resource allocation strategies in an uncertain decision-making environment, considering both uncertain service availability and accessibility. The study explores the performances of different modeling approaches (i.e., deterministic, stochastic programming, and robust optimization) to reflect various risk preferences. The models are evaluated in a case study of Singapore and results demonstrate that stochastic modeling methods in general offers more robust allocation strategies compared to deterministic approaches in achieving high coverage to critical infrastructures under risks. This general modeling framework can be applied to other emergency service applications, such as, locating medical emergency services. The development of renewable energy infrastructure system development aims to answer the following key research questions: (1) is the renewable energy an economically viable solution? (2) what are the energy distribution and infrastructure system requirements to support such energy supply systems in hedging against potential risks? (3) how does the energy system adapt the dynamics from evolving technology and societal needs in the transition into a renewable energy based society? The study of Renewable Energy System Planning with Risk Management incorporates risk management into its strategic planning of the supply chains. The physical design and operational management are integrated as a whole in seeking mitigations against the

  8. Bringing social standards into project evaluation under dynamic uncertainty.

    PubMed

    Knudsen, Odin K; Scandizzo, Pasquale L

    2005-04-01

    Society often sets social standards that define thresholds of damage to society or the environment above which compensation must be paid to the state or other parties. In this article, we analyze the interdependence between the use of social standards and investment evaluation under dynamic uncertainty where a negative externality above a threshold established by society requires an assessment and payment of damages. Under uncertainty, the party considering implementing a project or new technology must not only assess when the project is economically efficient to implement but when to abandon a project that could potentially exceed the social standard. Using real-option theory and simple models, we demonstrate how such a social standard can be integrated into cost-benefit analysis through the use of a development option and a liability option coupled with a damage function. Uncertainty, in fact, implies that both parties interpret the social standard as a target for safety rather than an inflexible barrier that cannot be overcome. The larger is the uncertainty, in fact, the greater will be the tolerance for damages in excess of the social standard from both parties. PMID:15876217

  9. Comminution of Ceramic Materials Under High-Shear Dynamic Compaction

    NASA Astrophysics Data System (ADS)

    Homel, Michael; Loiseau, Jason; Higgins, Andrew; Herbold, Eric; Hogan, Jamie

    The post-failure ``granular flow'' response of high-strength lightweight ceramics has important implications on the materials' effectiveness for ballistic protection. We study the dynamic compaction and shear flow of ceramic fragments and powders using computational and experimental analysis of a collapsing thick-walled cylinder geometry. Using newly developed tools for mesoscale simulation of brittle materials, we study the effect of fracture, comminution, shear-enhanced dilatation, and frictional contact on the continuum compaction response. Simulations are directly validated through particle Doppler velocimetry measurements at the inner surface of the cylindrical powder bed. We characterize the size distribution and morphologies of the initial and compacted material fragments to both validate the computational model and to elucidate the dominant failure processes. A portion of this work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344. Lawrence Livermore National Security, LLC. LLNL-ABS-678862.

  10. Bubble dynamics under acoustic excitation with multiple frequencies

    NASA Astrophysics Data System (ADS)

    Zhang, Y. N.; Zhang, Y. N.; Li, S. C.

    2015-01-01

    Because of its magnificent mechanical and chemical effects, acoustic cavitation plays an important role in a broad range of biomedical, chemical and mechanical engineering problems. Particularly, irradiation of the multiple frequency acoustic wave could enhance the effects of cavitation. The advantages of employment of multi-frequency ultrasonic field include decreasing the cavitation thresholds, promoting cavitation nuclei generation, increasing the mass transfer and improving energy efficiency. Therefore, multi-frequency ultrasonic systems are employed in a variety of applications, e.g., to enhance the intensity of sonoluminenscence, to increase efficiency of sonochemical reaction, to improve the accuracy of ultrasound imaging and the efficiency of tissue ablation. Compared to single-frequency systems, a lot of new features of bubble dynamics exist in multi-frequency systems, such as special properties of oscillating bubbles, unique resonances in the bubble response curves, and unusual chaotic behaviours. In present paper, the underlying mechanisms of the cavitation effects under multi-frequency acoustical excitation are also briefly introduced.

  11. Role of Tropomodulin’s Leucine Rich Repeat Domain in the Formation of Neurite-like Processes

    PubMed Central

    2015-01-01

    Actin dynamics is fundamental for neurite development; monomer depolymerization from pointed ends is rate-limiting in actin treadmilling. Tropomodulins (Tmod) make up a family of actin pointed end-capping proteins. Of the four known isoforms, Tmod1–Tmod3 are expressed in brain cells. We investigated the role of Tmod’s C-terminal (LRR) domain in the formation of neurite-like processes by overexpressing Tmod1 and Tmod2 with deleted or mutated LRR domains in PC12 cells, a model system used to study neuritogenesis. Tmod1 overexpression results in a normal quantity and a normal length of processes, while Tmod2 overexpression reduces both measures. The Tmod2 overexpression phenotype is mimicked by overexpression of Tmod1 with the LRR domain removed or with three point mutations in the LRR domain that disrupt exposed clusters of conserved residues. Removal of Tmod2’s LRR domain does not significantly alter the outgrowth of neurite-like processes compared to that of Tmod2. Overexpression of chimeras with the N-terminal and C-terminal domains switched between Tmod1 and Tmod2 reinforces the idea that Tmod1’s LRR domain counteracts the reductive effect of the Tmod N-terminal domain upon formation of processes while Tmod2’s LRR domain does not. We suggest that the TM-dependent actin capping ability of both Tmods inhibits the formation of processes, but in Tmod1, this inhibition can be controlled via its LRR domain. Circular dichroism, limited proteolysis, and molecular dynamics demonstrate structural differences in the C-terminal region of the LRR domains of Tmod1, Tmod2, and the Tmod1 mutant. PMID:24746171

  12. Evaluation of a human neurite growth assay as specific screen for developmental neurotoxicants.

    PubMed

    Krug, Anne K; Balmer, Nina V; Matt, Florian; Schönenberger, Felix; Merhof, Dorit; Leist, Marcel

    2013-12-01

    Organ-specific in vitro toxicity assays are often highly sensitive, but they lack specificity. We evaluated here examples of assay features that can affect test specificity, and some general procedures are suggested on how positive hits in complex biological assays may be defined. Differentiating human LUHMES cells were used as potential model for developmental neurotoxicity testing. Forty candidate toxicants were screened, and several hits were obtained and confirmed. Although the cells had a definitive neuronal phenotype, the use of a general cell death endpoint in these cultures did not allow specific identification of neurotoxicants. As alternative approach, neurite growth was measured as an organ-specific functional endpoint. We found that neurite extension of developing LUHMES was specifically inhibited by diverse compounds such as colchicine, vincristine, narciclasine, rotenone, cycloheximide, or diquat. These compounds reduced neurite growth at concentrations that did not compromise cell viability, and neurite growth was affected more potently than the integrity of developed neurites of mature neurons. A ratio of the EC50 values of neurite growth inhibition and cell death of >4 provided a robust classifier for compounds associated with a developmental neurotoxic hazard. Screening of unspecific toxicants in the test system always yielded ratios <4. The assay identified also compounds that accelerated neurite growth, such as the rho kinase pathway modifiers blebbistatin or thiazovivin. The negative effects of colchicine or rotenone were completely inhibited by a rho kinase inhibitor. In summary, we suggest that assays using functional endpoints (neurite growth) can specifically identify and characterize (developmental) neurotoxicants. PMID:23670202

  13. Nanomaterials under extreme environments: A study of structural and dynamic properties using reactive molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Shekhar, Adarsh

    Nanotechnology is becoming increasingly important with the continuing advances in experimental techniques. As researchers around the world are trying to expand the current understanding of the behavior of materials at the atomistic scale, the limited resolution of equipment, both in terms of time and space, act as roadblocks to a comprehensive study. Numerical methods, in general and molecular dynamics, in particular act as able compliment to the experiments in our quest for understanding material behavior. In this research work, large scale molecular dynamics simulations to gain insight into the mechano-chemical behavior under extreme conditions of a variety of systems with many real world applications. The body of this work is divided into three parts, each covering a particular system: 1) Aggregates of aluminum nanoparticles are good solid fuel due to high flame propagation rates. Multi-million atom molecular dynamics simulations reveal the mechanism underlying higher reaction rate in a chain of aluminum nanoparticles as compared to an isolated nanoparticle. This is due to the penetration of hot atoms from reacting nanoparticles to an adjacent, unreacted nanoparticle, which brings in external heat and initiates exothermic oxidation reactions. 2) Cavitation bubbles readily occur in fluids subjected to rapid changes in pressure. We use billion-atom reactive molecular dynamics simulations on a 163,840-processor BlueGene/P supercomputer to investigate chemical and mechanical damages caused by shock-induced collapse of nanobubbles in water near amorphous silica. Collapse of an empty nanobubble generates high-speed nanojet, resulting in the formation of a pit on the surface. The pit contains a large number of silanol groups and its volume is found to be directly proportional to the volume of the nanobubble. The gas-filled bubbles undergo partial collapse and consequently the damage on the silica surface is mitigated. 3) The structure and dynamics of water confined in

  14. Interface dynamics under nonequilibrium conditions: from a self-propelled droplet to dynamic pattern evolution.

    PubMed

    Chen, Y-J; Yoshikawa, K

    2011-04-01

    In this article, we describe the instability of a contact line under nonequilibrium conditions mainly based on the results of our recent studies. Two experimental examples are presented: the self-propelled motion of a liquid droplet and spontaneous dynamic pattern formation. For the self-propelled motion of a droplet, we introduce an experiment in which a droplet of aniline sitting on an aqueous layer moves spontaneously at an air-water interface. The spontaneous symmetry breaking of Marangoni-driven spreading causes regular motion. In a circular Petri dish, the droplet exhibits either beeline motion or circular motion. On the other hand, we show the emergence of a dynamic labyrinthine pattern caused by dewetting of a metastable thin film from the air-water interface. The contact line between the organic phase and the aqueous phase forms a unique spatio-temporal pattern characterized as a dynamic labyrinth. Motion of the contact line is controlled by diffusion processes. We propose a theoretical model to interpret essential aspects of the observed dynamic behavior. PMID:21509663

  15. Relaxation dynamics of lysozyme in solution under pressure: Combining molecular dynamics simulations and quasielastic neutron scattering

    NASA Astrophysics Data System (ADS)

    Calandrini, V.; Hamon, V.; Hinsen, K.; Calligari, P.; Bellissent-Funel, M.-C.; Kneller, G. R.

    2008-04-01

    This paper presents a study of the influence of non-denaturing hydrostatic pressure on the relaxation dynamics of lysozyme in solution, which combines molecular dynamics simulations and quasielastic neutron scattering experiments. We compare results obtained at ambient pressure and at 3 kbar. Experiments have been performed at pD 4.6 and at a protein concentration of 60 mg/ml. For both pressures we checked the monodispersity of the protein solution by small angle neutron scattering. To interpret the simulation results and the experimental data, we adopt the fractional Ornstein-Uhlenbeck process as a model for the internal relaxation dynamics of the protein. On the experimental side, global protein motions are accounted for by the model of free translational diffusion, neglecting the much slower rotational diffusion. We find that the protein dynamics in the observed time window from about 1 to 100 ps is slowed down under pressure, while its fractal characteristics is preserved, and that the amplitudes of the motions are reduced by about 20%. The slowing down of the relaxation is reduced with increasing q-values, where more localized motions are seen.

  16. Dynamics of transitions between capillary stable states under weightlessness

    NASA Astrophysics Data System (ADS)

    Srikanth, Praveen

    The study of two phase systems with one of the phases obstructing the other is of importance in a lot of fields. Liquid droplets in airways and air bubbles in the blood stream both fall under this category of problems. Helium bubbles in hydrazine fuel lines of satellites also have been found to cause frequent thruster shutdown and also seriously affect spacecraft control. Studies have been carried out until now to look at static equilibrium topologies and stability of such two phase systems in straight, bent and laterally compressed capillaries. In this investigation we look at the dynamics of the transitions between the stable topologies identified for a straight cylindrical capillary. The break up of the interface could adversely affect system performance. OpenFOAM is used to compute transitions from a stable droplet to a plug or the reverse by suitably adding or removing the obstructing phase through inlet patches on the wall of the cylinder. The main parameters presented are the non-dimensional energy, non-dimensional transition times, non-dimensional transition volumes and the general dynamics of the transitions itself. Before computing transitions the static equilibrium topologies computed by OpenFOAM are compared with those predicted by Surface Evolver and are found to be within acceptable deviations. The grid dependence of these transitions has also been studied. Transitions are computed for contact angles in the range of 10° to 170°. Different modes of transitions are observed depending on the contact angle of the case for both the types of transitions. The transition volumes are compared to the volume of existence limits for the corresponding initial topology at a particular contact angle for both the transitions.

  17. Growth, collapse, and stalling in a mechanical model for neurite motility

    NASA Astrophysics Data System (ADS)

    Recho, Pierre; Jerusalem, Antoine; Goriely, Alain

    2016-03-01

    Neurites, the long cellular protrusions that form the routes of the neuronal network, are capable of actively extending during early morphogenesis or regenerating after trauma. To perform this task, they rely on their cytoskeleton for mechanical support. In this paper, we present a three-component active gel model that describes neurites in the three robust mechanical states observed experimentally: collapsed, static, and motile. These states arise from an interplay between the physical forces driven by growth of the microtubule-rich inner core of the neurite and the acto-myosin contractility of its surrounding cortical membrane. In particular, static states appear as a mechanical traction or compression balance of these two parallel structures. The model predicts how the response of a neurite to a towing force depends on the force magnitude and recovers the response of neurites to several drug treatments that modulate the cytoskeleton active and passive properties.

  18. A Farnesyltransferase Acts to Inhibit Ectopic Neurite Formation in C. elegans

    PubMed Central

    Carr, David; Sanchez-Alvarez, Leticia; Imai, Janice H.; Slatculescu, Cristina; Noblett, Nathaniel; Mao, Lei; Beese, Lorena; Colavita, Antonio

    2016-01-01

    Genetic pathways that regulate nascent neurite formation play a critical role in neuronal morphogenesis. The core planar cell polarity components VANG-1/Van Gogh and PRKL-1/Prickle are involved in blocking inappropriate neurite formation in a subset of motor neurons in C. elegans. A genetic screen for mutants that display supernumerary neurites was performed to identify additional factors involved in this process. This screen identified mutations in fntb-1, the β subunit of farnesyltransferase. We show that fntb-1 is expressed in neurons and acts cell-autonomously to regulate neurite formation. Prickle proteins are known to be post-translationally modified by farnesylation at their C-terminal CAAX motifs. We show that PRKL-1 can be recruited to the plasma membrane in both a CAAX-dependent and CAAX-independent manner but that PRKL-1 can only inhibit neurite formation in a CAAX-dependent manner. PMID:27300162

  19. The neuritic plaque facilitates pathological conversion of tau in an Alzheimer's disease mouse model

    PubMed Central

    Li, Tong; Braunstein, Kerstin E.; Zhang, Juhong; Lau, Ashley; Sibener, Leslie; Deeble, Christopher; Wong, Philip C.

    2016-01-01

    A central question in Alzheimer's Disease (AD) is whether the neuritic plaque is necessary and sufficient for the development of tau pathology. Hyperphosphorylation of tau is found within dystrophic neurites surrounding β-amyloid deposits in AD mouse models but the pathological conversion of tau is absent. Likewise, expression of a human tau repeat domain in mice is insufficient to drive the pathological conversion of tau. Here we developed an Aβ-amyloidosis mouse model that expresses the human tau repeat domain and show that in these mice, the neuritic plaque facilitates the pathological conversion of wild-type tau. We show that this tau fragment seeds the neuritic plaque-dependent pathological conversion of wild-type tau that spreads from the cortex and hippocampus to the brain stem. These results establish that in addition to the neuritic plaque, a second determinant is required to drive the conversion of wild-type tau. PMID:27373369

  20. A three-dimensional image processing program for accurate, rapid, and semi-automated segmentation of neuronal somata with dense neurite outgrowth

    PubMed Central

    Ross, James D.; Cullen, D. Kacy; Harris, James P.; LaPlaca, Michelle C.; DeWeerth, Stephen P.

    2015-01-01

    Three-dimensional (3-D) image analysis techniques provide a powerful means to rapidly and accurately assess complex morphological and functional interactions between neural cells. Current software-based identification methods of neural cells generally fall into two applications: (1) segmentation of cell nuclei in high-density constructs or (2) tracing of cell neurites in single cell investigations. We have developed novel methodologies to permit the systematic identification of populations of neuronal somata possessing rich morphological detail and dense neurite arborization throughout thick tissue or 3-D in vitro constructs. The image analysis incorporates several novel automated features for the discrimination of neurites and somata by initially classifying features in 2-D and merging these classifications into 3-D objects; the 3-D reconstructions automatically identify and adjust for over and under segmentation errors. Additionally, the platform provides for software-assisted error corrections to further minimize error. These features attain very accurate cell boundary identifications to handle a wide range of morphological complexities. We validated these tools using confocal z-stacks from thick 3-D neural constructs where neuronal somata had varying degrees of neurite arborization and complexity, achieving an accuracy of ≥95%. We demonstrated the robustness of these algorithms in a more complex arena through the automated segmentation of neural cells in ex vivo brain slices. These novel methods surpass previous techniques by improving the robustness and accuracy by: (1) the ability to process neurites and somata, (2) bidirectional segmentation correction, and (3) validation via software-assisted user input. This 3-D image analysis platform provides valuable tools for the unbiased analysis of neural tissue or tissue surrogates within a 3-D context, appropriate for the study of multi-dimensional cell-cell and cell-extracellular matrix interactions. PMID

  1. Influence of cAMP and protein kinase A on neurite length from spiral ganglion neurons

    PubMed Central

    Xu, Ningyong; Engbers, Jonathan; Khaja, Sobia; Xu, Linjing; Clark, J. Jason; Hansen, Marlan R.

    2011-01-01

    Regrowth of peripheral spiral ganglion neuron (SGN) fibers is a primary objective in efforts to improve cochlear implant outcomes and to potentially reinnervate regenerated hair cells. Cyclic adenosine monophosphate (cAMP) regulates neurite growth and guidance via activation of protein kinase A (PKA) and Exchange Protein directly Activated by Cylic AMP (Epac). Here we explored the effects of cAMP signaling on SGN neurite length in vitro. We find that the cAMP analog, cpt-cAMP, exerts a biphasic effect on neurite length; increasing length at lower concentrations and reducing length at higher concentrations. This biphasic response occurs in cultures plated on laminin, fibronectin, or tenascin C suggesting that it is not substrate dependent. cpt-cAMP also reduces SGN neurite branching. The Epac-specific agonist, 8-pCPT-2’-O-Me-cAMP, does not alter SGN neurite length. Constitutively active PKA isoforms strongly inhibit SGN neurite length similar to higher levels of cAMP. Chronic membrane depolarization activates PKA in SGNs and also inhibits SGN neurite length. However, inhibition of PKA fails to rescue neurite length in depolarized cultures implying that activation of PKA is not necessary for the inhibition of SGN neurite length by chronic depolarization. Expression of constitutively active phosphatidylinositol 3-kinase, but not c-Jun N-terminal kinase, isoforms partially rescues SGN neurite length in the presence of activated PKA. Taken together, these results suggest that activation of cAMP/PKA represents a potential strategy to enhance SGN fiber elongation following deafness; however such therapies will likely require careful titration so as to simultaneously promote rather than inhibit nerve fiber regeneration. PMID:22154930

  2. Coastal-zone biogeochemical dynamics under global warming

    SciTech Connect

    Mackenzie, F.T.; Ver, L.M.; Lerman, A.

    2000-03-01

    The coastal zone, consisting of the continental shelves to a depth of 200 meters, including bays, lagoons, estuaries, and near-shore banks, is an environment that is strongly affected by its biogeochemical and physical interactions with reservoirs in the adjacent domains of land, atmosphere, open ocean, and marine sediments. Because the coastal zone is smaller in volume and area coverage relative to the open ocean, it traditionally has been studied as an integral part of the global oceans. In this paper, the authors show by numerical modeling that it is important to consider the coastal zone as an entity separate from the open ocean in any assessment of future Earth-system response under human perturbation. Model analyses for the early part of the 21st century suggest that the coastal zone plays a significant modifying role in the biogeochemical dynamics of the carbon cycle and the nutrient cycles coupled to it. This role is manifested in changes in primary production, storage, and/or export of organic matter, its remineralization, and calcium carbonate precipitation--all of which determine the state of the coastal zone with respect to exchange of CO{sub 2} with the atmosphere. Under a scenario of future reduced or complete cessation of the thermohaline circulation (THC) of the global oceans, coastal waters become an important sink for atmospheric CO{sub 2}, as opposed to the conditions in the past and present, when coastal waters are believed to be a source of CO{sub 2} to the atmosphere. Profound changes in coastal-zone primary productivity underscore the important role of phosphorus as a limiting nutrient. In addition, calculations indicate that the saturation state of coastal waters with respect to carbonate minerals will decline by {approximately}15% by the year 2030. Any future slowdown in the THC of the oceans will increase slightly the rate of decline in saturation state.

  3. Performance of HEPA filters under hot dynamic conditions

    SciTech Connect

    Frankum, D.P.; Costigan, G.

    1995-02-01

    Accidents in nuclear facilities involving fires may have implications upon the ventilation systems where high efficiency particulate air (HEPA) filters are used to minimise the airborne release of radioactive or toxic particles. The Filter Development Section at Harwell Laboratory has been investigating the effect of temperature on the performance of HEPA filters under hot dynamic conditions[{sub 1}] for a number of years. The test rig is capable of delivering air flows of 10001/s (at ambient conditions) at temperatures up to 500{degrees}C, where measurements of the penetration and pressure drop across the filter are obtained. This paper reports the experiments on different constructions of HEPA filters; rectangular and circular. The filters were tested at an air temperature of 200{degrees}C for up to 48 hours at the rated airflow to assess their performance. The penetration measurements for rectangular filters were observed to be below 0.021% after prolonged operation. In a number of cases, holes appeared along the pleat creases of circular filters although the penetration remained below 1%. The sealing gasket for these filters was noted to deform with temperature, permitting a leakage path. A prototype high strength circular filter was evaluated at temperatures of up to 400{degrees}C with a penetration less than 0.65%.

  4. Dynamic behavior of thermionic dispenser cathodes under ion bombardment

    NASA Astrophysics Data System (ADS)

    Cortenraad, R.; van der Gon, A. W. Denier; Brongersma, H. H.; Gärtner, G.; Raasch, D.; Manenschijn, A.

    2001-04-01

    We have investigated the surface coverage and electron emission of thermionic dispenser cathodes during 3 keV Ar+ ion bombardment, thereby simulating the bombardment of the cathodes by residual gases that takes place in cathode-ray tubes as used in television sets. During the ion bombardment at the operating temperature of 1030 °C, a dynamic equilibrium is established between the sputter removal and resupply mechanisms of the Ba and O atoms that form the dipole layer on the cathode substrate. We demonstrated that the performance of the cathodes under ion bombardment is governed by the O removal and resupply rates. It was found that the Ba resupply rate is almost an order of magnitude higher than the O resupply rate, but that the Ba can only be present on the surface bound to O atoms. Therefore, the Ba/O ratio is approximately equal to unity during the ion bombardment. Based on the investigations of the removal and resupply processes, we proposed a model that accurately describes the surface coverage and electron emission during the ion bombardment, including the dependence of the ion flux and cathode temperature.

  5. Analyzing freeway traffic under congestion: Traffic dynamics approach

    SciTech Connect

    Nam, D.H.; Drew, D.R.

    1998-05-01

    This paper presents an analysis of freeway traffic flows under congestion based on the principle of traffic dynamics, using the example of recurring congestion. Queuing and discharging mechanisms are analyzed using the fundamental concept of conservation of vehicles. These analysis results are applied for reviewing the two conventional macroscopic analysis tools, deterministic queuing analysis and shock-wave analysis. Comparative study results have demonstrated that (1) the two methods are fundamentally different from the traffic modeling point of view; (2) deterministic queuing analysis always underestimates the overall magnitude of delays compared to shock-wave analysis; and (3) the area between the demand and the capacity curves in a queuing diagram is analytically equivalent to total vehicle-hours of travel in congestion as opposed to the widely accepted total vehicle-hours of delay. The study results imply that the guidelines of the 1994 Highway Capacity Manual may result in the underestimation of congestion-related statistics. For the purposes of illustration and verification, a numerical example problem is provided.

  6. Behavior of sodium borosilicate glasses under compression using molecular dynamics

    SciTech Connect

    Kilymis, D. A.; Ispas, S.; Delaye, J.-M.

    2015-09-07

    We have performed classical molecular dynamics simulations in order to study the changes under compression in the local and medium range structural properties of three sodium borosilicate glasses with varying sodium content. These glasses have been isostatically compressed up to 20 GPa and then decompressed in order to analyze the different mechanisms that affect densification, alongside with the permanent modifications of the structure after a full compression/decompression cycle. The results show that the atomic packing is the prominent characteristic that governs the amount of densification in the glass, as well as the setup of the permanent densification. During compression, the bulk modulus increases linearly up to approximately 15 GPa and more rapidly for higher pressures, a behavior which is reflected on the rate of increase of the average coordination for B and Na. Radial distribution functions at different pressures during the cycle help to quantify the amount of distortions in the elementary structural units, with a pronounced shortening of the Na–Na and Na–O bond lengths during compression. A subsequent decomposition of the glassy matrix into elementary Voronoi volumes verifies the high compressibility of Na-rich regions.

  7. Skyrmion dynamics in chiral ferromagnets under spin-transfer torque

    NASA Astrophysics Data System (ADS)

    Komineas, Stavros; Papanicolaou, Nikos

    2015-11-01

    We study the dynamics of skyrmions under spin-transfer torque in Dzyaloshinskii-Moriya materials with easy-axis anisotropy. In particular, we study the motion of a topological skyrmion with skyrmion number Q =1 and a nontopological skyrmionium with Q =0 using their linear momentum, virial relations, and numerical simulations. The nontopological Q =0 skyrmionium is accelerated in the direction of the current flow and it either reaches a steady state with constant velocity, or it is elongated to infinity. The steady-state velocity is given by a balance between current and dissipation and has an upper limit. In contrast, the topological Q =1 skyrmion converges to a steady state with constant velocity at an angle to the current flow. When the spin current stops the Q =1 skyrmion is spontaneously pinned, whereas the Q =0 skyrmionium continues propagation. Exact solutions for the propagating skyrmionium are identified as solutions of equations given numerically in a previous work. Further exact results for propagating skyrmions are given in the case of the pure exchange model. The traveling solutions provide arguments that a spin-polarized current will cause rigid motion of a skyrmion or a skyrmionium.

  8. Stress relaxation in vanadium under shock and shockless dynamic compression

    SciTech Connect

    Kanel, G. I.; Razorenov, S. V.; Garkushin, G. V.; Savinykh, A. S.; Zaretsky, E. B.

    2015-07-28

    Evolutions of elastic-plastic waves have been recorded in three series of plate impact experiments with annealed vanadium samples under conditions of shockless and combined ramp and shock dynamic compression. The shaping of incident wave profiles was realized using intermediate base plates made of different silicate glasses through which the compression waves were entered into the samples. Measurements of the free surface velocity histories revealed an apparent growth of the Hugoniot elastic limit with decreasing average rate of compression. The growth was explained by “freezing” of the elastic precursor decay in the area of interaction of the incident and reflected waves. A set of obtained data show that the current value of the Hugoniot elastic limit and plastic strain rate is rather associated with the rate of the elastic precursor decay than with the local rate of compression. The study has revealed the contributions of dislocation multiplications in elastic waves. It has been shown that independently of the compression history the material arrives at the minimum point between the elastic and plastic waves with the same density of mobile dislocations.

  9. Molecular dynamics simulation of VN thin films under indentation

    NASA Astrophysics Data System (ADS)

    Fu, Tao; Peng, Xianghe; Huang, Cheng; Yin, Deqiang; Li, Qibin; Wang, Zhongchang

    2015-12-01

    We investigated with molecular dynamics simulation the mechanical responses of VN (0 0 1) thin films subjected to indentation with a diamond columnar indenter. We calculated the generalized stacking-fault energies as a function of the displacement in the rbond2 1 1 0lbond2 directions on the {0 0 1}, {1 1 0}, and {1 1 1} planes, and analyzed systematically the microstructures and their evolution during the indentation with the centro-symmetry parameters and the slices of the VN films. We found the slips on {1 1 0}rbond2 1 1 0lbond2 of the VN film under indentation at the initial stage. With the increase of indentation depth, slips are also activated on {1 1 1}rbond2 1 1 0lbond2 and {1 0 0}rbond2 0 1 1lbond2 systems. We further found that the slip system is determined by the stacking-fault energy rather than the layer spacing. The indentations with other different parameters were also performed, and the results further prove the validity of the conclusion.

  10. Buckling of circular cylindrical shells under dynamically applied axial loads

    NASA Technical Reports Server (NTRS)

    Tulk, J. D.

    1972-01-01

    A theoretical and experimental study was made of the buckling characteristics of perfect and imperfect circular cylindrical shells subjected to dynamic axial loading. Experimental data included dynamic buckling loads (124 data points), high speed photographs of buckling mode shapes and observations of the dynamic stability of shells subjected to rapidly applied sub-critical loads. A mathematical model was developed to describe the dynamic behavior of perfect and imperfect shells. This model was based on the Donnell-Von Karman compatibility and equilibrium equations and had a wall deflection function incorporating five separate modes of deflection. Close agreement between theory and experiment was found for both dynamic buckling strength and buckling mode shapes.

  11. Microfluidic Generation of Haptotactic Gradients through 3D Collagen Gels for Enhanced Neurite Growth

    PubMed Central

    Sundararaghavan, Harini G.; Masand, Shirley N.

    2011-01-01

    Abstract We adapted a microfluidic system used previously to generate durotactic gradients of stiffness in a 3D collagen gel, to produce haptotactic gradients of adhesive ligands through the collagen gel. Oligopeptide sequences that included bioactive peptide sequences from laminin, YIGSR, or IKVAV, were grafted separately onto type I collagen using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Solutions of peptide-grafted collagen and untreated collagen were then used as source and sink input solutions, respectively, in an H-shaped microfluidic network fabricated using traditional soft lithography. One-dimensional gradients of the peptide-grafted collagen solution were generated in the channel that connected the source and sink channels, and these gradients became immobilized upon self-assembly of the collagen into a 3D fibrillar gel. The slope and average concentration of the gradients were adjusted by changing the concentration of the source solutions and by changing the length of the cross-channel. A separate, underlying channel in the microfluidic construct allowed the introduction of a chick embryo dorsal root ganglion into the network. Neurites from these explants grew significantly longer up steep gradients of YIGSR, but shallow gradients of IKVAV in comparison to untreated collagen controls. When these two gradients were presented in combination, the bias in growth acceleration was the largest and most consistent. No differences were observed in the number of neurites choosing to grow up or down the gradients in any condition. These results suggest that the incorporation of distinct gradients of multiple bioactive ligands can improve directional acceleration of regenerating axons. PMID:21473683

  12. C dynamics in Amazonian podzols under climate change

    NASA Astrophysics Data System (ADS)

    Nunan, Naoise; Soro, Andre; Potard, Kevin; Pouteau, Valerie; Montes, Celia; Melphi, Adolpho; Lucas, Yves; Chenu, Claire

    2016-04-01

    It has recently been shown that the C stocks in Amazonian podzols are very large. They are much larger than was previously thought, particularly in the Bh horizon, which has been estimated to contain in excess of 13Pg C for Amazonia alone. It is predicted that the changes in regional climate will result in a drier soil water regime which may affect the C dynamics in these soils that are usually saturated. In order to determine the vulnerability to change of the organic C contained in the Amazonian podzols, a series of incubation experiments were established in which the effects of a number of different factors on microbial decomposition were measured. The direct effect of drier soil water regimes was tested by incubating undisturbed cores from the Bh horizon at a range of matric potentials (saturation to wilting point). Contrary to what is usually found in soils, no significant difference in mineralisation was found among matric potentials, suggesting that other factors control microbial mineralisation of this organic C. The effect of nitrogen additions, of anaerobic conditions and of the addition labile C substrate were also tested on undisturbed cores of the Bh horizon of the podzols. Samples incubated under aerobic conditions produced 3 times more CO2 than samples incubated under anaerobic conditions, whilst samples incubated under aerobic conditions with the addition of N mineralised 6.7 times more CO2 than the anaerobic samples. The addition of labile C did not have a significant effect on C mineralisation, i.e. there was no priming effect. The combined addition of labile C and mineral N did not stimulate C mineralisation more than N additions alone. By extrapolating the differences obtained here to the whole of the Amazonian podzols, it is estimated that changes in conditions which result in an increase in O2 and in N (i.e. changes in vegetation due to increases in dry periods with the establishment of a savanna for example) in the soil will cause the release

  13. Design improvement and dynamic finite element analysis of novel ITI dental implant under dynamic chewing loads.

    PubMed

    Cheng, Yung-Chang; Lin, Deng-Huei; Jiang, Cho-Pei; Lee, Shyh-Yuan

    2015-01-01

    The main aim of this article was to introduce the application of a uniform design for experimental methods to drop the micromotion of a novel ITI dental implant model under the dynamic loads. Combining the characteristics of the traditional ITI and Nano-Tite implants, a new implant with concave holes has been constructed. Compared to the traditional ITI dental implant model, the micromotion of the new dental implant model was significantly reduced by explicit dynamic finite element analysis. From uniform design of experiments, the dynamic finite element analysis method was applied to caluculated the maximum micromotion of the full model. Finally, the chief design in all the experiment simulations which cause the minimum micromotion is picked as the advanced model of the design. Related to the original design, which was associated with a micromotion of 45.11 μm, the micromotion of the improved version was 31.37 μm, for an improvement rate of 30.5%. PMID:26406049

  14. Evolution of specialization under non-equilibrium population dynamics.

    PubMed

    Nurmi, Tuomas; Parvinen, Kalle

    2013-03-21

    We analyze the evolution of specialization in resource utilization in a mechanistically underpinned discrete-time model using the adaptive dynamics approach. We assume two nutritionally equivalent resources that in the absence of consumers grow sigmoidally towards a resource-specific carrying capacity. The consumers use resources according to the law of mass-action with rates involving trade-off. The resulting discrete-time model for the consumer population has over-compensatory dynamics. We illuminate the way non-equilibrium population dynamics affect the evolutionary dynamics of the resource consumption rates, and show that evolution to the trimorphic coexistence of a generalist and two specialists is possible due to asynchronous non-equilibrium population dynamics of the specialists. In addition, various forms of cyclic evolutionary dynamics are possible. Furthermore, evolutionary suicide may occur even without Allee effects and demographic stochasticity. PMID:23306058

  15. Examining Hyporheic Dynamics Under Fluctuating Stream Stage Conditions

    NASA Astrophysics Data System (ADS)

    Dudley-Southern, M. J.; Binley, A. M.; Pates, J.; Wynn, P.

    2013-12-01

    Gaining river systems that are connected to groundwaters with increasing nitrate levels are at risk from increased nitrate loading. The consequences of greater nitrate transfer to surface waters are uncertain, but attenuation of nitrate waters at the groundwater -surface water interface may help to reduce the ecological impact on receiving surface waters. The majority of studies of groundwater-surface water interactions have focussed on low flow conditions. Some studies have revealed evidence of biogeochemical reactions occurring at a greater depth in the subsurface than could be supported by mixing between surface water and groundwater under low flow conditions. We believe that, under particular geomorphological settings, short-lived changes in groundwater flow pathways may lead to transformations of the extent of hyporheic flow, and thus potentially impact on biogeochemical cycling at this interface. Here we focus on the influence of changes in stream stage, during storm events, on the extent of the hyporheic zone. It is hypothesised that when there is a large sudden change in surface water level, ambient groundwater gradients can undergo a transient reversal, leading to temporary downwelling of surface water which alters the physical and biogeochemical conditions in the subsurface. Physically, downwelling surface water increases the residence time of water within the subsurface by impeding the movement of upwelling groundwater. Biogeochemically, downwelling surface water supplies, for example, dissolved organic carbon to the subsurface, potentially supporting favourable redox conditions for nutrient transformations. To evaluate this concept, the dynamics of groundwater-surface water interactions are being examined at an instrumented gaining reach of the River Leith, Cumbria, UK. Experimental evidence is being gathered by continuously logged hydraulic head data, electrical geophysics and temperature profiles. These data are supported by repeat spot sampling

  16. Transcriptome dynamics of Pseudomonas putida KT2440 under water stress.

    PubMed

    Gülez, Gamze; Dechesne, Arnaud; Workman, Christopher T; Smets, Barth F

    2012-02-01

    Water deprivation can be a major stressor to microbial life in surface and subsurface soil. In unsaturated soils, the matric potential (Ψ(m)) is often the main component of the water potential, which measures the thermodynamic availability of water. A low matric potential usually translates into water forming thin liquid films in the soil pores. Little is known of how bacteria respond to such conditions, where, in addition to facing water deprivation that might impair their metabolism, they have to adapt their dispersal strategy as swimming motility may be compromised. Using the pressurized porous surface model (PPSM), which allows creation of thin liquid films by controlling Ψ(m), we examined the transcriptome dynamics of Pseudomonas putida KT2440. We identified the differentially expressed genes in cells exposed to a mild matric stress (-0.4 MPa) for 4, 24, or 72 h. The major response was detected at 4 h before gradually disappearing. Upregulation of alginate genes was notable in this early response. Flagellar genes were not downregulated, and the microarray data even suggested increasing expression as the stress prolonged. Moreover, we tested the effect of polyethylene glycol 8000 (PEG 8000), a nonpermeating solute often used to simulate Ψ(m), on the gene expression profile and detected a different profile than that observed by directly imposing Ψ(m). This study is the first transcriptome profiling of KT2440 under directly controlled Ψ(m) and also the first to show the difference in gene expression profiles between a PEG 8000-simulated and a directly controlled Ψ(m). PMID:22138988

  17. Pn anisotropic tomography and dynamics under eastern Tibetan plateau

    NASA Astrophysics Data System (ADS)

    Lei, Jianshe; Li, Yuan; Xie, Furen; Teng, Jiwen; Zhang, Guangwei; Sun, Changqing; Zha, Xiaohui

    2014-03-01

    We present a new anisotropic tomographic model of the uppermost mantle around eastern Tibet using Pn traveltime data from a newly deployed temporary seismic array and recent observation bulletins of Chinese provincial networks. Our results are generally consistent with previous results but provide new insights into the dynamics of Tibetan plateau. Prominent high-velocity (high-V) anomalies are visible under Alashan block and Qaidam and Sichuan basins, which clearly outline their tectonic margins. A distinct high-V zone representing the double-sided subduction of Indo-Eurasian plates is imaged from Lhasa block to the south of Qaidam basin. A pronounced low-velocity (low-V) zone is observed from Songpan-Ganzi block to southern Chuan-Dian diamond block, suggesting the existence of hot material upwelling there. Crustal strong earthquakes frequently occurred around high-V anomalies or transition zones from high-V to low-V anomalies, suggesting that these earthquakes could be related to lateral heterogeneities in the mantle. The Pn fast direction approximately rotates around Eastern Himalayan Syntaxis, and it is tangential to the margins of Sichuan basin, suggesting that the mantle material flow of Tibetan plateau may have affected east China. In the Yunnan region to the south of 26°N, the Pn fast direction is different from SKS splitting results, indicating that the mantle lithosphere could be mechanically decoupled at certain depth below the uppermost mantle, which might be attributable to the subduction of Indian (or Burma) slab. Although the correlation between anisotropy and velocity is complicated, anisotropy strength could be associated with the pattern of velocity anomalies in the region.

  18. Dynamics of non-Brownian fiber suspensions under periodic shear.

    PubMed

    Franceschini, Alexandre; Filippidi, Emmanouela; Guazzelli, Elisabeth; Pine, David J

    2014-09-21

    We report experiments studying the dynamics of dense non-Brownian fiber suspensions subjected to periodic oscillatory shear. We find that periodic shear initially causes fibers to collide and to undergo irreversible diffusion. As time progresses, the fibers tend to orient in the vorticity direction while the number of collisions decreases. Ultimately, the system goes to one of two steady states: an absorbing steady state, where collisions cease and the fibers undergo reversible trajectories; an active state, where fibers continue to collide causing them to diffuse and undergo irreversible trajectories. Collisions between fibers can be characterized by an effective volume fraction Φ with a critical volume fraction Φc that separates absorbing from active (diffusing) steady states. The effective volume fraction Φ depends on the mean fiber orientation and thus decreases in time as fibers progressively orient under periodic shear. In the limit that the temporal evolution of Φ is slow compared to the activity relaxation time τ, all the data for all strain amplitudes and all concentrations can be scaled onto a single master curve with a functional dependence well-described by t(-β/ν)R(e(-t)R), where tR is the rescaled time. As Φ → Φc, τ diverges. Therefore, for experiments in which Φ(t) starts above Φc but goes to a steady state below Φc, departures from scaling are observed for Φ very near Φc. The critical exponents are measured to be β = 0.84 ± 0.04 and ν = 1.1 ± 0.1, which is consistent with the Manna universality class for directed percolation. PMID:25068577

  19. FGF-2 deficiency causes dysregulation of Arhgef6 and downstream targets in the cerebral cortex accompanied by altered neurite outgrowth and dendritic spine morphology.

    PubMed

    Baum, Philip; Vogt, Miriam A; Gass, Peter; Unsicker, Klaus; von Bohlen Und Halbach, Oliver

    2016-05-01

    Fibroblast growth factor 2 (FGF-2) is an abundant growth factor in the brain and exerts multiple functions on neural cells ranging from cell division, cell fate determination to differentiation. However, many details of the molecular mechanisms underlying the diverse functions of FGF-2 are poorly understood. In a comparative microarray analysis of motor sensory cortex (MSC) tissue of adult knockout (FGF-2(-/-)) and control (FGF-2(+/+)) mice, we found a substantial number of regulated genes, which are implicated in cytoskeletal machinery dynamics. Specifically, we found a prominent downregulation of Arhgef6. Arhgef6 mRNA was significantly reduced in the FGF-2(-/-) cortex, and Arhgef6 protein virtually absent, while RhoA protein levels were massively increased and Cdc42 protein levels were reduced. Since Arhgef6 is localized to dendritic spines, we next analyzed dendritic spines of adult FGF2(-/-) and control mouse cortices. Spine densities were significantly increased, whereas mean length of spines on dendrites of layer V of MSC neurons in adult FGF-2(-/-) mice was significantly decreased as compared to respective controls. Furthermore, neurite length in dissociated cortical cultures from E18 FGF-2(-/-) mice was significantly reduced at DIV7 as compared to wildtype neurons. Despite the fact that altered neuronal morphology and alterations in dendritic spines were observed, FGF-2(-/-) mice behave relatively unsuspicious in several behavioral tasks. However, FGF-2(-/-) mice exhibited decreased thermal pain sensitivity in the hotplate-test. PMID:26970009

  20. Retinoic acid receptor beta2 and neurite outgrowth in the adult mouse spinal cord in vitro.

    PubMed

    Corcoran, Jonathan; So, Po-Lin; Barber, Robert D; Vincent, Karen J; Mazarakis, Nicholas D; Mitrophanous, Kyriacos A; Kingsman, Susan M; Maden, Malcolm

    2002-10-01

    Retinoic acid, acting through the nuclear retinoic acid receptor beta2 (RARbeta2), stimulates neurite outgrowth from peripheral nervous system tissue that has the capacity to regenerate neurites, namely, embryonic and adult dorsal root ganglia. Similarly, in central nervous system tissue that can regenerate, namely, embryonic mouse spinal cord, retinoic acid also stimulates neurite outgrowth and RARbeta2 is upregulated. By contrast, in the adult mouse spinal cord, which cannot regenerate, no such upregulation of RARbeta2 by retinoic acid is observed and no neurites are extended in vitro. To test our hypothesis that the upregulation of RARbeta2 is crucial to neurite regeneration, we have transduced adult mouse or rat spinal cord in vitro with a minimal equine infectious anaemia virus vector expressing RARbeta2. After transduction, prolific neurite outgrowth occurs. Outgrowth does not occur when the cord is transduced with a different isoform of RARbeta nor does it occur following treatment with nerve growth factor. These data demonstrate that RARbeta2 is involved in neurite outgrowth, at least in vitro, and that this gene may in the future be of some therapeutic use. PMID:12235288

  1. Neurite outgrowth at the interface of 2D and 3D growth environments

    NASA Astrophysics Data System (ADS)

    Kofron, Celinda M.; Fong, Vivian J.; Hoffman-Kim, Diane

    2009-02-01

    Growing neurons navigate complex environments, but in vitro systems for studying neuronal growth typically limit the cues to flat surfaces or a single type of cue, thereby limiting the resulting growth. Here we examined the growth of neurons presented with two-dimensional (2D) substrate-bound cues when these cues were presented in conjunction with a more complex three-dimensional (3D) architecture. Dorsal root ganglia (DRG) explants were cultured at the interface between a collagen I matrix and a glass coverslip. Laminin (LN) or chondroitin sulfate proteoglycans (CSPG) were uniformly coated on the surface of the glass coverslip or patterned in 50 µm tracks by microcontact printing. Quantitative analysis of neurite outgrowth with a novel grid system at multiple depths in the gel revealed several interesting trends. Most of the neurites extended at the surface of the gel when LN was presented whereas more neurites extended into the gel when CSPG was presented. Patterning of cues did not affect neurite density or depth of growth. However, neurite outgrowth near the surface of the gel aligned with LN patterns, and these extensions were significantly longer than neurites extended in other cultures. In interface cultures, DRG growth patterns varied with the type of cue where neurite density was higher in cultures presenting LN than in cultures presenting CSPG. These results represent an important step toward understanding how neurons integrate local structural and chemical cues to make net growth decisions.

  2. The neurite-initiating effect of microbial extracellular glycolipids in PC12 cells.

    PubMed

    Isoda, H; Shinmoto, H; Matsumura, M; Nakahara, T

    1999-09-01

    The effects of several kinds of microbial extracellular glycolipids on neurite initiation in PC12 cells were examined. Addition of mannosylerythritol lipid-A (MEL-A), MEL-B, and sophorose lipid (SL) to PC12 cells caused significant neurite outgrowth. Other glycolipids, such as polyol lipid (PL), rhamnose lipid (RL), succinoyl trehalose lipid-A (STL-A) and STL-B caused no neurite-initiation. MEL-A increased acetylcholine esterase (AChE) activity to an extent similar to nerve growth factor (NGF). However, MEL-A induced one or two long neurites from the cell body, while NGF induced many neurites. In addition, MEL-A-induced differentiation was transient, and after 48 h, percentage of cells with neurites started to decrease in contrast to neurons induced by NGF, which occurred in a time-dependent manner. MEL-A could induce neurite outgrowth after treatment of PC12 cells with an anti-NGF receptor antibody that obstructed NGF action. These results indicate that MEL-A and NGF induce differentiation of PC12 cells through different mechanisms. PMID:19003137

  3. 15d-prostaglandin J2 enhancement of nerve growth factor-induced neurite outgrowth is blocked by the chemoattractant receptor- homologous molecule expressed on T-helper type 2 cells (CRTH2) antagonist CAY10471 in PC12 cells.

    PubMed

    Hatanaka, Michiyoshi; Shibata, Norihiro; Shintani, Norihito; Haba, Ryota; Hayata, Atsuko; Hashimoto, Hitoshi; Baba, Akemichi

    2010-01-01

    The chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTH2) is the most recently identified prostaglandin (PG) receptor for both PGD(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). We examined the mechanism by which 15d-PGJ(2) enhances nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. CAY10471 (CRTH2 antagonist) inhibited both the neurite-promotion and p38 mitogen-activated protein (MAP) kinase phosphorylation induced by 15d-PGJ(2). In contrast, 13,14-dihydro-15-keto-PGD(2 )(DK-PGD(2)) (selective CRTH2 agonist) stimulated its phosphorylation but failed to produce neurite-promoting effects. These suggest, for the first time, the action of 15d-PGJ(2) is mediated by CRTH2, although the CRTH2 activation alone is insufficient for the underlying action. PMID:20424389

  4. Single Polymer Dynamics under Large Amplitude Oscillatory Extensional (LAOE) Flow

    NASA Astrophysics Data System (ADS)

    Zhou, Yuecheng; Schroeder, Charles M.

    Over the past two decades, advances in fluorescence imaging and particle manipulation have enabled the direct observation of single polymer dynamics in model flows such as shear flow and planar extensional flow. The vast majority of single polymer studies, however, has focused on chain dynamics using simple transient step forcing functions. In order to study single polymer dynamics in non-idealized model flows, there is a clear need to implement more complicated transient flow forcing functions. In bulk rheology, large amplitude oscillatory shear (LAOS) was widely used to study the linear and nonlinear viscoelasticity of materials, but not yet been applied to molecular rheology. In this work, we directly probe single polymer dynamics using oscillatory extensional flow in precisely controlled microfluidic devices. We are able to generate large and small amplitude sinusoidal oscillatory extensional flow in a cross-slot microfluidic device while imaging the conformational dynamics of a single polymer trapped at the stagnation point. In this flow, polymer chains are stretched, squeezed, and rotated between extensional/compressional axes in a highly dynamic and transient manner. Using this technique, we studied the dynamics and coil-stretch transition of a single λ-DNA as a function of the Weissenberg number (Wi) and Deborah number (De). Moreover, we use Brownian dynamics simulation to map a wide range of Pipkin space for polymers from linear steady-state conditions to non-linear unsteady-states. Our results reveal a critical Wi at the coil-stretch transition that is function of the De in LAOE flow. Department of Materials Science and Engineering.

  5. Examining Hyporheic Dynamics Under Fluctuating Stream Stage Conditions

    NASA Astrophysics Data System (ADS)

    Dudley-Southern, Marina; Binley, Andrew; Pates, Jackie; Wynn, Peter

    2014-05-01

    Gaining river systems that are connected to groundwaters with increasing nitrate levels are at risk from increased nitrate loading. The consequences of greater nitrate transfer to surface waters are uncertain, but attenuation of nitrate waters at the groundwater -surface water interface may help to reduce the ecological impact on receiving surface waters. The majority of studies of groundwater-surface water interactions have focussed on low flow conditions. Some studies have revealed evidence of biogeochemical reactions occurring at a greater depth in the subsurface than could be supported by mixing between surface water and groundwater under low flow conditions. We believe that, under particular geomorphological settings, short-lived changes in groundwater flow pathways may lead to transformations of the extent of hyporheic flow, and thus potentially impact on biogeochemical cycling at this interface. Here we focus on the influence of changes in stream stage, during storm events, on the extent of the hyporheic zone. It is hypothesised that when there is a large sudden change in surface water level, ambient groundwater gradients can undergo a transient reversal, leading to temporary downwelling of surface water which alters the physical and biogeochemical conditions in the subsurface. Physically, downwelling surface water increases the residence time of water within the subsurface by impeding the movement of upwelling groundwater. Biogeochemically, downwelling surface water supplies, for example, dissolved organic carbon to the subsurface, potentially supporting favourable redox conditions for nutrient transformations. To evaluate this concept, the dynamics of groundwater-surface water interactions are being examined at an instrumented gaining reach of the River Leith, Cumbria, UK. Experimental evidence is being gathered by continuously logged hydraulic head data, electrical geophysics and temperature profiles. These data are supported by repeat spot sampling

  6. Pseudo generators for under-resolved molecular dynamics

    NASA Astrophysics Data System (ADS)

    Bittracher, A.; Hartmann, C.; Junge, O.; Koltai, P.

    2015-09-01

    Many features of a molecule which are of physical interest (e.g. molecular conformations, reaction rates) are described in terms of its dynamics in configuration space. This article deals with the projection of molecular dynamics in phase space onto configuration space. Specifically, we study the situation that the phase space dynamics is governed by a stochastic Langevin equation and study its relation with the configurational Smoluchowski equation in the three different scaling regimes: Firstly, the Smoluchowski equations in non-Cartesian geometries are derived from the overdamped limit of the Langevin equation. Secondly, transfer operator methods are used to describe the metastable behaviour of the system at hand, and an explicit small-time asymptotics is derived on which the Smoluchowski equation turns out to govern the dynamics of the position coordinate (without any assumptions on the damping). By using an adequate reduction technique, these considerations are then extended to one-dimensional reaction coordinates. Thirdly, we sketch three different approaches to approximate the metastable dynamics based on time-local information only.

  7. Dynamic Stability of Uncertain Laminated Beams Under Subtangential Loads

    NASA Technical Reports Server (NTRS)

    Goyal, Vijay K.; Kapania, Rakesh K.; Adelman, Howard (Technical Monitor); Horta, Lucas (Technical Monitor)

    2002-01-01

    Because of the inherent complexity of fiber-reinforced laminated composites, it can be challenging to manufacture composite structures according to their exact design specifications, resulting in unwanted material and geometric uncertainties. In this research, we focus on the deterministic and probabilistic stability analysis of laminated structures subject to subtangential loading, a combination of conservative and nonconservative tangential loads, using the dynamic criterion. Thus a shear-deformable laminated beam element, including warping effects, is derived to study the deterministic and probabilistic response of laminated beams. This twenty-one degrees of freedom element can be used for solving both static and dynamic problems. In the first-order shear deformable model used here we have employed a more accurate method to obtain the transverse shear correction factor. The dynamic version of the principle of virtual work for laminated composites is expressed in its nondimensional form and the element tangent stiffness and mass matrices are obtained using analytical integration The stability is studied by giving the structure a small disturbance about an equilibrium configuration, and observing if the resulting response remains small. In order to study the dynamic behavior by including uncertainties into the problem, three models were developed: Exact Monte Carlo Simulation, Sensitivity Based Monte Carlo Simulation, and Probabilistic FEA. These methods were integrated into the developed finite element analysis. Also, perturbation and sensitivity analysis have been used to study nonconservative problems, as well as to study the stability analysis, using the dynamic criterion.

  8. Dynamics of range margins for metapopulations under climate change.

    PubMed

    Anderson, B J; Akçakaya, H R; Araújo, M B; Fordham, D A; Martinez-Meyer, E; Thuiller, W; Brook, B W

    2009-04-22

    We link spatially explicit climate change predictions to a dynamic metapopulation model. Predictions of species' responses to climate change, incorporating metapopulation dynamics and elements of dispersal, allow us to explore the range margin dynamics for two lagomorphs of conservation concern. Although the lagomorphs have very different distribution patterns, shifts at the edge of the range were more pronounced than shifts in the overall metapopulation. For Romerolagus diazi (volcano rabbit), the lower elevation range limit shifted upslope by approximately 700 m. This reduced the area occupied by the metapopulation, as the mountain peak currently lacks suitable vegetation. For Lepus timidus (European mountain hare), we modelled the British metapopulation. Increasing the dispersive estimate caused the metapopulation to shift faster on the northern range margin (leading edge). By contrast, it caused the metapopulation to respond to climate change slower, rather than faster, on the southern range margin (trailing edge). The differential responses of the leading and trailing range margins and the relative sensitivity of range limits to climate change compared with that of the metapopulation centroid have important implications for where conservation monitoring should be targeted. Our study demonstrates the importance and possibility of moving from simple bioclimatic envelope models to second-generation models that incorporate both dynamic climate change and metapopulation dynamics. PMID:19324811

  9. Dynamics of range margins for metapopulations under climate change

    PubMed Central

    Anderson, B.J.; Akçakaya, H.R.; Araújo, M.B.; Fordham, D.A.; Martinez-Meyer, E.; Thuiller, W.; Brook, B.W.

    2009-01-01

    We link spatially explicit climate change predictions to a dynamic metapopulation model. Predictions of species' responses to climate change, incorporating metapopulation dynamics and elements of dispersal, allow us to explore the range margin dynamics for two lagomorphs of conservation concern. Although the lagomorphs have very different distribution patterns, shifts at the edge of the range were more pronounced than shifts in the overall metapopulation. For Romerolagus diazi (volcano rabbit), the lower elevation range limit shifted upslope by approximately 700 m. This reduced the area occupied by the metapopulation, as the mountain peak currently lacks suitable vegetation. For Lepus timidus (European mountain hare), we modelled the British metapopulation. Increasing the dispersive estimate caused the metapopulation to shift faster on the northern range margin (leading edge). By contrast, it caused the metapopulation to respond to climate change slower, rather than faster, on the southern range margin (trailing edge). The differential responses of the leading and trailing range margins and the relative sensitivity of range limits to climate change compared with that of the metapopulation centroid have important implications for where conservation monitoring should be targeted. Our study demonstrates the importance and possibility of moving from simple bioclimatic envelope models to second-generation models that incorporate both dynamic climate change and metapopulation dynamics. PMID:19324811

  10. ROCK inhibition enhances neurite outgrowth in neural stem cells by upregulating YAP expression in vitro

    PubMed Central

    Jia, Xu-feng; Ye, Fei; Wang, Yan-bo; Feng, Da-xiong

    2016-01-01

    Spontaneous axonal regeneration of neurons does not occur after spinal cord injury because of inhibition by myelin and other inhibitory factors. Studies have demonstrated that blocking the Rho/Rho-kinase (ROCK) pathway can promote neurite outgrowth in spinal cord injury models. In the present study, we investigated neurite outgrowth and neuronal differentiation in neural stem cells from the mouse subventricular zone after inhibition of ROCK in vitro. Inhibition of ROCK with Y-27632 increased neurite length, enhanced neuronal differentiation, and upregulated the expression of two major signaling pathway effectors, phospho-Akt and phospho-mitogen-activated protein kinase, and the Hippo pathway effector YAP. These results suggest that inhibition of ROCK mediates neurite outgrowth in neural stem cells by activating the Hippo signaling pathway. PMID:27482229

  11. ANALYSIS OF THE STRUCTURE OF MAGNETIC FIELDS THAT INDUCED INHIBITION OF STIMULATED NEURITE OUTGROWTH

    EPA Science Inventory

    The important experiments showing nonlinear amplitude dependences of the neurite outgrowth in pheochromocytoma nerve cells due to ELF magnetic field exposure had been carried out in a nonuniform ac magnetic field. The nonuniformity entailed larger than expected variances in magne...

  12. Expression of Ndufb11 encoding the neuronal protein 15.6 during neurite outgrowth and development.

    PubMed

    Gurok, Ulf; Bork, Kaya; Nuber, Ulrike; Spörle, Ralf; Nöhring, Sabine; Horstkorte, Rüdiger

    2007-01-01

    Neurite outgrowth (e.g. axonal or dendrite outgrowth) of neurons is necessary for the development and functioning of the central nervous system. It is well accepted that the differentiation of neurons and neurite outgrowth involve alterations in gene expression. Furthermore, mitochondria play a role in different aspects of neurite outgrowth. Here we show that the expression of Ndufb11, a gene encoding the mitochondrial protein NP15.6 is decreased in the course of neuronal differentiation. NP15.6 is homologous to the bovine protein ESSS, a component of the mitochondrial complex 1. The homologous human NDUFB11 gene is localized to Xp11.3-Xp11.23, a region associated with neurogenetic disorders. The down-regulation of NP15.6 correlates with neurite outgrowth of PC12 cells induced by nerve growth factor. Furthermore, we analyzed the expression of Ndufb11 in the embryonic and adult mouse. PMID:16962385

  13. Morphological assessment of neurite outgrowth in hippocampal neuron-astrocyte co-cultures.

    PubMed

    Giordano, Gennaro; Costa, Lucio G

    2012-05-01

    Neurite outgrowth is a fundamental event in brain development, as well as in regeneration of damaged neurons. Astrocytes play a major role in neuritogenesis, by expressing and releasing factors that facilitate neurite outgrowth, such as extracellular matrix proteins, and factors that can inhibit neuritogenesis, such as the chondroitin sulfate proteoglycan neurocan. In this unit we describe a noncontact co-culture system of hippocampal neurons and cortical (or hippocampal) astrocytes for measurement of neurite outgrowth. Hippocampal pyramidal neurons are plated on glass coverslips, which are inverted onto an astrocyte feeder layer, allowing exposure of neurons to astrocyte-derived factors without direct contact between these two cell types. After co-culture, neurons are stained and photographed, and processes are assessed morphologically using Metamorph software. This method allows exposing astrocytes to various agents before co-culture in order to assess how these exposures may influence the ability of astrocytes to foster neurite outgrowth. PMID:22549268

  14. Gait recognition under carrying condition: a static dynamic fusion method

    NASA Astrophysics Data System (ADS)

    Yu, Guan; Li, Chang-Tsun; Hu, Yongjian

    2012-06-01

    When an individual carries an object, such as a briefcase, conventional gait recognition algorithms based on average silhouette/Gait Energy Image (GEI) do not always perform well as the object carried may have the potential of being mistakenly regarded as a part of the human body. To solve such a problem, in this paper, instead of directly applying GEI to represent the gait information, we propose a novel dynamic feature template for classification. Based on this extracted dynamic information and some static feature templates (i.e., head part and trunk part), we cast gait recognition on the large USF (University of South Florida) database by adopting a static/dynamic fusion strategy. For the experiments involving carrying condition covariate, significant improvements are achieved when compared with other classic algorithms.

  15. Design of three-dimensional engineered protein hydrogels for tailored control of neurite growth.

    PubMed

    Lampe, Kyle J; Antaris, Alexander L; Heilshorn, Sarah C

    2013-03-01

    The design of bioactive materials allows tailored studies probing cell-biomaterial interactions, however, relatively few studies have examined the effects of ligand density and material stiffness on neurite growth in three-dimensions. Elastin-like proteins (ELPs) have been designed with modular bioactive and structural regions to enable the systematic characterization of design parameters within three-dimensional (3-D) materials. To promote neurite out-growth and better understand the effects of common biomaterial design parameters on neuronal cultures we here focused on the cell-adhesive ligand density and hydrogel stiffness as design variables for ELP hydrogels. With the inherent design freedom of engineered proteins these 3-D ELP hydrogels enabled decoupled investigations into the effects of biomechanics and biochemistry on neurite out-growth from dorsal root ganglia. Increasing the cell-adhesive RGD ligand density from 0 to 1.9×10(7)ligands μm(-3) led to a significant increase in the rate, length, and density of neurite out-growth, as quantified by a high throughput algorithm developed for dense neurite analysis. An approximately two-fold improvement in total neurite out-growth was observed in materials with the higher ligand density at all time points up to 7 days. ELP hydrogels with initial elastic moduli of 0.5, 1.5, or 2.1kPa and identical RGD ligand densities revealed that the most compliant materials led to the greatest out-growth, with some neurites extending over 1800μm by day 7. Given the ability of ELP hydrogels to efficiently promote neurite out-growth within defined and tunable 3-D microenvironments these materials may be useful in developing therapeutic nerve guides and the further study of basic neuron-biomaterial interactions. PMID:23128159

  16. Functional coordination of muscles underlying changes in behavioural dynamics.

    PubMed

    Vernooij, Carlijn A; Rao, Guillaume; Perdikis, Dionysios; Huys, Raoul; Jirsa, Viktor K; Temprado, Jean-Jacques

    2016-01-01

    The dynamical systems approach addresses Bernstein's degrees of freedom problem by assuming that the neuro-musculo-skeletal system transiently assembles and dismantles its components into functional units (or synergies) to meet task demands. Strikingly, little is known from a dynamical point of view about the functioning of the muscular sub-system in this process. To investigate the interaction between the dynamical organisation at muscular and behavioural levels, we searched for specific signatures of a phase transition in muscular coordination when a transition is displayed at the behavioural level. Our results provide evidence that, during Fitts' task when behaviour switches to a different dynamical regime, muscular activation displays typical signatures of a phase transition; a reorganisation in muscular coordination patterns accompanied by a peak in the variability of muscle activation. This suggests that consistent changes occur in coordination processes across the different levels of description (i.e., behaviour and muscles). Specifically, in Fitts' task, target size acts as a control parameter that induces a destabilisation and a reorganisation of coordination patterns at different levels of the neuro-musculo-skeletal system. PMID:27282349

  17. Functional coordination of muscles underlying changes in behavioural dynamics

    PubMed Central

    Vernooij, Carlijn A.; Rao, Guillaume; Perdikis, Dionysios; Huys, Raoul; Jirsa, Viktor K.; Temprado, Jean-Jacques

    2016-01-01

    The dynamical systems approach addresses Bernstein’s degrees of freedom problem by assuming that the neuro-musculo-skeletal system transiently assembles and dismantles its components into functional units (or synergies) to meet task demands. Strikingly, little is known from a dynamical point of view about the functioning of the muscular sub-system in this process. To investigate the interaction between the dynamical organisation at muscular and behavioural levels, we searched for specific signatures of a phase transition in muscular coordination when a transition is displayed at the behavioural level. Our results provide evidence that, during Fitts’ task when behaviour switches to a different dynamical regime, muscular activation displays typical signatures of a phase transition; a reorganisation in muscular coordination patterns accompanied by a peak in the variability of muscle activation. This suggests that consistent changes occur in coordination processes across the different levels of description (i.e., behaviour and muscles). Specifically, in Fitts’ task, target size acts as a control parameter that induces a destabilisation and a reorganisation of coordination patterns at different levels of the neuro-musculo-skeletal system. PMID:27282349

  18. Soil phosphorus dynamics under sprinkler and furrow irrigation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Furrow irrigation detaches and transports soil particles and subsequently nutrients such as phosphorus. To reduce the risk of erosion and offsite phosphorus movement, producers can convert from furrow to sprinkler irrigation. We completed research on soil phosphorus dynamics in furrow versus sprin...

  19. Amyloid β-Protein as a Substrate Interacts with Extracellular Matrix to Promote Neurite Outgrowth

    NASA Astrophysics Data System (ADS)

    Koo, Edward H.; Park, Lisa; Selkoe, Dennis J.

    1993-05-01

    Progressive deposition of amyloid β-protein (Aβ) in brain parenchyma and blood vessels is a characteristic feature of Alzheimer disease. Recent evidence suggests that addition of solubilized synthetic Aβ to medium may produce toxic or trophic effects on cultured hippocampal neurons. Because soluble Aβ may not accumulate in significant quantities in brain, we asked whether immobilized Aβ peptide as a substrate alters neurite outgrowth from cultured rat peripheral sensory neurons. This paradigm may closely mimic the conditions in Alzheimer disease brain tissue, in which neurites contact insoluble, extracellular aggregates of β-amyloid. We detected no detrimental effects of Aβ substrate on neurite outgrowth. Rather, Aβ in combination with low doses of laminin or fibronectin enhanced neurite out-growth from these neuronal explants. Our results suggest that insoluble Aβ in the cerebral neuropil may serve as a neurite-promoting matrix, perhaps explaining the apparent regenerative response of neurites observed around amyloid plaques in Alzheimer disease. Moreover, in concert with the recent discovery of Aβ production by cultured neurons, our data suggest that Aβ plays a normal physiological role in brain by complexing with the extracellular matrix.

  20. Hypothermia-induced neurite outgrowth is mediated by tumor necrosis factor-alpha.

    PubMed

    Schmitt, Katharina R L; Boato, Francesco; Diestel, Antje; Hechler, Daniel; Kruglov, Andrei; Berger, Felix; Hendrix, Sven

    2010-07-01

    Systemic or brain-selective hypothermia is a well-established method for neuroprotection after brain trauma. There is increasing evidence that hypothermia exerts beneficial effects on the brain and may also support regenerative responses after brain damage. Here, we have investigated whether hypothermia influences neurite outgrowth in vitro via modulation of the post-injury cytokine milieu. Organotypic brain slices were incubated: deep hypothermia (2 h at 17 degrees C), rewarming (2 h up to 37 degrees C), normothermia (20 h at 37 degrees C). Neurite density and cytokine release (IL 1beta, IL-6, IL-10, and TNF-alpha) were investigated after 24 h. For functional analysis mice deficient in NT-3/NT-4 and TNF-alpha as well as the TNF-alpha inhibitor etanercept were used. Hypothermia led to a significant increase of neurite outgrowth, which was independent of neurotrophin signaling. In contrast to other cytokines investigated, TNF-alpha secretion by organotypic brain slices was significantly increased after deep hypothermia. Moreover, hypothermia-induced neurite extension was abolished after administration of the TNF-alpha inhibitor and in TNF-alpha knockout mice. We demonstrate that TNF-alpha is responsible for inducing neurite outgrowth in the context of deep hypothermia and rewarming. These data suggest that hypothermia not only exerts protective effects in the CNS but may also support neurite outgrowth as a potential mechanism of regeneration. PMID:20070303

  1. Survival and neurite growth of chick embryo spinal cord cells in serum-free culture.

    PubMed

    Tanaka, H; Obata, K

    1982-07-01

    Cell survival and neurite growth were investigated in serum-free spinal cord cell cultures on polyornithine coating (PORN). Cells were obtained from 6- or 7-day-old chick embryos. Isolated spinal cord cells required promoting factors for their survival and neurite growth. The survival-promoting factors were initially present in spinal cord cells. High density cultures, co-cultures with spinal cord explants, and spinal cord extract promoted survival of isolated spinal cord cells in MEM with no additives. Other tissue extracts (brain, liver, heart and skeletal muscle), serum, and serum-free conditioned medium (SF-CM) of muscle or glioma C6 cells also promoted survival. The active substances in the brain extract and SF-CM were shown to be protein and were separated into 3 fractions (approximately molecular weight 150,000, 70,000, 40,000) by gel filtration chromatography. Survival and neurite growth were suggested to be promoted by different factors because: (1) survival was promoted by both tissue extract and SF-CM, but neurite growth was promoted only by SF-CM; (2) the neurite growth-stimulating activity of SF-CM was lost following dialysis and heat (100 degrees C, 2 min) treatment; however, the survival-promoting activity was not. It was also suggested that spinal cord cells produce neurite growth promoting factors, but did not initially contain these factors. PMID:7104764

  2. MorphoNeuroNet: an automated method for dense neurite network analysis.

    PubMed

    Pani, Giuseppe; De Vos, Winnok H; Samari, Nada; de Saint-Georges, Louis; Baatout, Sarah; Van Oostveldt, Patrick; Benotmane, Mohammed Abderrafi

    2014-02-01

    High content cell-based screens are rapidly gaining popularity in the context of neuronal regeneration studies. To analyze neuronal morphology, automatic image analysis pipelines have been conceived, which accurately quantify the shape changes of neurons in cell cultures with non-dense neurite networks. However, most existing methods show poor performance for well-connected and differentiated neuronal networks, which may serve as valuable models for inter alia synaptogenesis. Here, we present a fully automated method for quantifying the morphology of neurons and the density of neurite networks, in dense neuronal cultures, which are grown for more than 10 days. MorphoNeuroNet, written as a script for ImageJ, Java based freeware, automatically determines various morphological parameters of the soma and the neurites (size, shape, starting points, and fractional occupation). The image analysis pipeline consists of a multi-tier approach in which the somas are segmented by adaptive region growing using nuclei as seeds, and the neurites are delineated by a combination of various intensity and edge detection algorithms. Quantitative comparison showed a superior performance of MorphoNeuroNet to existing analysis tools, especially for revealing subtle changes in thin neurites, which have weak fluorescence intensity compared to the rest of the network. The proposed method will help determining the effects of compounds on cultures with dense neurite networks, thereby boosting physiological relevance of cell-based assays in the context of neuronal diseases. PMID:24222510

  3. In vitro neurite guidance effects induced by polylysine pinstripe micropatterns with polylysine background.

    PubMed

    Joo, Sunghoon; Kang, Kyungtae; Nam, Yoonkey

    2015-08-01

    Engineered culture substrates with chemical neurite guidance cues have been used for studying the mechanism of axon pathfinding at cellular level. In this study, we designed a novel poly-l-lysine (PLL) micropattern ("pinstripe micropattern") to investigate how the same biomolecules with slightly different surface concentration can affect in vitro neuronal growth. The pinstripe micropattern was fabricated by stamping PLL on a PLL-coated glass coverslip, which resulted in denser PLL lines and a less-dense PLL background. There were two effects of the substrate on cultured primary hippocampal neuron: neurite initiation and growth cone turning. Although the whole surface was permissive for neurite outgrowth, we observed that the growth direction of neurites had a strong tendency to follow the stamped PLL line patterns with PLL background. However, the micropattern did not affect the spreading of cell body on the substrate. According to these investigations, we concluded that the PLL pinstripe pattern with PLL background, which had the step difference of polylysine concentrations, would be very useful for designing novel cell assays for the investigation of neurite guidance mechanisms, and suggested it as a new design method for controlling the direction of neurite growth on in vitro neural network. PMID:25630479

  4. Multiscale Analysis of Neurite Orientation and Spatial Organization in Neuronal Images.

    PubMed

    Singh, Pankaj; Negi, Pooran; Laezza, Fernanda; Papadakis, Manos; Labate, Demetrio

    2016-10-01

    The spatial organization of neurites, the thin processes (i.e., dendrites and axons) that stem from a neuron's soma, conveys structural information required for proper brain function. The alignment, direction and overall geometry of neurites in the brain are subject to continuous remodeling in response to healthy and noxious stimuli. In the developing brain, during neurogenesis or in neuroregeneration, these structural changes are indicators of the ability of neurons to establish axon-to-dendrite connections that can ultimately develop into functional synapses. Enabling a proper quantification of this structural remodeling would facilitate the identification of new phenotypic criteria to classify developmental stages and further our understanding of brain function. However, adequate algorithms to accurately and reliably quantify neurite orientation and alignment are still lacking. To fill this gap, we introduce a novel algorithm that relies on multiscale directional filters designed to measure local neurites orientation over multiple scales. This innovative approach allows us to discriminate the physical orientation of neurites from finer scale phenomena associated with local irregularities and noise. Building on this multiscale framework, we also introduce a notion of alignment score that we apply to quantify the degree of spatial organization of neurites in tissue and cultured neurons. Numerical codes were implemented in Python and released open source and freely available to the scientific community. PMID:27369547

  5. Myoblasts and myoblast-conditioned medium attract the earliest spinal neurites from frog embryos.

    PubMed Central

    McCaig, C D

    1986-01-01

    A study was made of the capacity of newly segmented somites, unsegmented mesoderm and medium conditioned by each of these tissues to attract the growth of the earliest spinal neurites from the neural tube of Xenopus laevis in tissue culture. When presented with segmented somitic myoblasts or sheets of skin, spinal neurites grew selectively towards the somitic myoblasts. Neurites were not attracted specifically to somitic myoblasts from their own rostrocaudal level. A variable proportion of myoblasts from unsegmented caudal mesoderm differentiated and elongated in co-culture with neural tube and skin. These myoblasts also attracted neural outgrowths, but only if present in sufficient numbers. An agar slab containing medium conditioned by the presence of segmented myoblasts for 1 day attracted neurite outgrowths. A source of medium conditioned by the presence of undifferentiated, unsegmented myotomal mesoderm alone did not attract neurite outgrowths. Nerve growth factor (NGF) at a range of concentrations in the agar source (500-10,000 ng/ml) did not attract the earliest neurite outgrowths. It is concluded that the earliest skeletal myoblasts from Xenopus laevis embryos may attract neural outgrowths by releasing a soluble factor. Myoblasts may have to develop to the stage of somite segmentation before secretion of such an agent begins. The release of a myoblast-derived factor so early in development may assist directed nerve growth in vivo. Images Plate 1 Plate 2 PMID:3795063

  6. Oxytocin Increases Neurite Length and Expression of Cytoskeletal Proteins Associated with Neuronal Growth.

    PubMed

    Lestanova, Z; Bacova, Z; Kiss, A; Havranek, T; Strbak, V; Bakos, J

    2016-06-01

    Neuropeptide oxytocin acts as a growth and differentiation factor; however, its effects on neurite growth are poorly understood. The aims of the present study were (1) to evaluate time effects of oxytocin on expression of nestin and MAP2; (2) to measure the effect of oxytocin on gene expression of β-actin, vimentin, cofilin, and drebrin; and (3) to measure changes in neurite length and number in response to oxytocin/oxytocin receptor antagonist L-371,257. Exposure of SH-SY5Y cells to 1 μM oxytocin resulted in a significant increase in gene expression and protein levels of nestin after 12, 24, and 48 h. Oxytocin treatment induced no changes in gene expression of MAP2; however, a decrease of protein levels was observed in all time intervals. Gene expression of β-actin, vimentin, and drebrin increased in response to oxytocin. Oxytocin induced significant elongation of neurites after 12, 24, and 48 h. No change in neurite length was observed in the presence of the combination of retinoic acid and oxytocin receptor antagonist L-371,257. Oxytocin treatment for 12 h increased the number of neurites. Overall, the present data suggest that oxytocin contributes to the regulation of expression of cytoskeletal proteins associated with growth of neuronal cones and induces neurite elongation mediated by oxytocin receptors at least in certain types of neuronal cells. PMID:26474566

  7. Sigma-1 Receptor Enhances Neurite Elongation of Cerebellar Granule Neurons via TrkB Signaling

    PubMed Central

    Kimura, Yuriko; Fujita, Yuki; Shibata, Kumi; Mori, Megumi; Yamashita, Toshihide

    2013-01-01

    Sigma-1 receptor (Sig-1R) is an integral membrane protein predominantly expressed in the endoplasmic reticulum. Sig-1R demonstrates a high affinity to various synthetic compounds including well-known psychotherapeutic drugs in the central nervous system (CNS). For that, it is considered as an alternative target for psychotherapeutic drugs. On the cellular level, when Sig-1R is activated, it is known to play a role in neuroprotection and neurite elongation. These effects are suggested to be mediated by its ligand-operated molecular chaperone activity, and/or upregulation of various Ca2+ signaling. In addition, recent studies show that Sig-1R activation induces neurite outgrowth via neurotrophin signaling. Here, we tested the hypothesis that Sig-1R activation promotes neurite elongation through activation of tropomyosin receptor kinase (Trk), a family of neurotrophin receptors. We found that 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate (PRE-084), a selective Sig-1R agonist, significantly promoted neurite outgrowth, and K252a, a Trk inhibitor, attenuated Sig-1R-mediated neurite elongation in cerebellar granule neurons (CGNs). Moreover, we revealed that Sig-1R interacts with TrkB, and PRE-084 treatment enhances phosphorylation of Y515, but not Y706. Thus, our results indicate that Sig-1R activation promotes neurite outgrowth in CGNs through Y515 phosphorylation of TrkB. PMID:24116072

  8. Control of Retinal Ganglion Cell Positioning and Neurite Growth: Combining 3D Printing with Radial Electrospun Scaffolds.

    PubMed

    Kador, Karl E; Grogan, Shawn P; Dorthé, Erik W; Venugopalan, Praseeda; Malek, Monisha F; Goldberg, Jeffrey L; D'lima, Darryl D

    2016-02-01

    Retinal ganglion cells (RGCs) are responsible for the transfer of signals from the retina to the brain. As part of the central nervous system, RGCs are unable to regenerate following injury, and implanted cells have limited capacity to orient and integrate in vivo. During development, secreted guidance molecules along with signals from extracellular matrix and the vasculature guide cell positioning, for example, around the fovea, and axon outgrowth; however, these changes are temporally regulated and are not the same in the adult. Here, we combine electrospun cell transplantation scaffolds capable of RGC neurite guidance with thermal inkjet 3D cell printing techniques capable of precise positioning of RGCs on the scaffold surface. Optimal printing parameters are developed for viability, electrophysiological function and, neurite pathfinding. Different media, commonly used to promote RGC survival and growth, were tested under varying conditions. When printed in growth media containing both brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), RGCs maintained survival and normal electrophysiological function, and displayed radial axon outgrowth when printed onto electrospun scaffolds. These results demonstrate that 3D printing technology may be combined with complex electrospun surfaces in the design of future retinal models or therapies. PMID:26729061

  9. Minimum Wind Dynamic Soaring Trajectories under Boundary Layer Thickness Limits

    NASA Astrophysics Data System (ADS)

    Bousquet, Gabriel; Triantafyllou, Michael; Slotine, Jean-Jacques

    2015-11-01

    Dynamic soaring is the flight technique where a glider, either avian or manmade, extracts its propulsive energy from the non-uniformity of horizontal winds. Albatrosses have been recorded to fly an impressive 5000 km/week at no energy cost of their own. In the sharp boundary layer limit, we show that the popular image, where the glider travels in a succession of half turns, is suboptimal for travel speed, airspeed, and soaring ability. Instead, we show that the strategy that maximizes the three criteria simultaneously is a succession of infinitely small arc-circles connecting transitions between the calm and windy layers. The model is consistent with the recordings of albatross flight patterns. This lowers the required wind speed for dynamic soaring by over 50% compared to previous beliefs. In the thick boundary layer limit, energetic considerations allow us to predict a minimum wind gradient necessary for sustained soaring consistent with numerical models.

  10. Studies of TLP dynamic response under wind, waves and current

    NASA Astrophysics Data System (ADS)

    Gu, Jia-yang; Yang, Jian-min; Lv, Hai-ning

    2012-09-01

    Investigated is the coupled response of a tension leg platform (TLP) for random waves. Inferred are the mass matrix, coupling stiffness matrix, damping matrix in the vibration differential equation and external load of TLP in moving coordinating system. Infinitesimal method is applied to divide columns and pontoons into small parts. Time domain motion equation is solved by Runge-Kutta integration scheme. Jonswap spectrum is simulated in the random wave, current is simulated by linear interpolation, and NPD spectrum is applied as wind spectrum. The Monte Carlo method is used to simulate random waves and fluctuated wind. Coupling dynamic response, change of tendon tension and riser tension in different sea conditions are analyzed by power spectral density (PSD). The influence of approach angle on dynamic response of TLP and tendon tension is compared.

  11. Forward dynamics simulation of human body under tilting perturbations

    NASA Astrophysics Data System (ADS)

    Naderi, D.; Pasha Zanoosi, A. A.; Sadeghi-Mehr, M.

    2012-02-01

    Human body uses different strategies to maintain its stability and these strategies vary from fixed-foot strategies to strategies which foot is moved in order to increase the support base. Tilting movement of foot is one type of the perturbations usually is exposed to human body. In the presence of such perturbations human body must employ appropriate reactions to prevent threats like falling. But it is not clear that how human body maintains its stability by central nervous system (CNS). At present study it is tried that by presenting a musculoskeletal model of human lower extremity with four links, three degrees of freedom (DOF) and eight skeletal muscles, the level of muscle activations causes the maintenance of stability, be investigated. Using forward dynamics solution, leads to a more general problem, rather than inverse dynamics. Hence, forward dynamics solution by forward optimization has been used for solving this highly nonlinear problem. To this end, first the system's equations of motion has been derived using lagrangian dynamics. Eight Hill-type muscles as actuators of the system were modeled. Because determination of muscle forces considering their number is an undetermined problem, optimization of an appropriate goal function should be practiced. For optimization problem, the characteristics of genetic algorithms as a method based on direct search, and the direct collocation method, has been profited. Also by considering requirements of problem, some constraints such as conservation of model stability are entered into optimization procedure. Finally to investigate validation of model, the results from optimization and experimental data are compared and good agreements are obtained.

  12. Cell patterning with a heptagon acoustic tweezer--application in neurite guidance.

    PubMed

    Gesellchen, F; Bernassau, A L; Déjardin, T; Cumming, D R S; Riehle, M O

    2014-07-01

    Accurate control over positioning of cells is a highly desirable feature in tissue engineering applications since it allows, for example, population of substrates in a controlled fashion, rather than relying on random seeding. Current methods to achieve a differential distribution of cells mostly use passive patterning methods to change chemical, mechanical or topographic properties of surfaces, making areas differentially permissive to the adhesion of cells. However, these methods have no ad hoc control over the actual deposition of cells. Direct patterning methods like bioprinting offer good control over cell position, but require sophisticated instrumentation and are often cost- and time-intensive. Here, we present a novel electronically controlled method of generating dynamic cell patterns by acoustic trapping of cells at a user-determined position, with a heptagonal acoustic tweezer device. We demonstrate the capability of the device to create complex patterns of cells using the device's ability to re-position acoustic traps by using a phase shift in the acoustic wave, and by switching the configuration of active piezoelectric transducers. Furthermore, we show that by arranging Schwann cells from neonatal rats in a linear pattern we are able to create Bands of Büngner-like structures on a non-structured surface and demonstrate that these features are able to guide neurite outgrowth from neonatal rat dorsal root ganglia. PMID:24817215

  13. Dynamics of a bacterial flagellum under reverse rotation.

    PubMed

    Adhyapak, Tapan Chandra; Stark, Holger

    2016-07-01

    To initiate tumbling of an E. coli, one of the helical flagella reverses its sense of rotation. It then transforms from its normal form first to the transient semicoiled state and subsequently to the curly-I state. The dynamics of polymorphism is effectively modeled by describing flagellar elasticity through an extended Kirchhoff free energy. However, the complete landscape of the free energy remains undetermined because the ground state energies of the polymorphic forms are not known. We investigate how variations in these ground state energies affect the dynamics of a reversely rotated flagellum of a swimming bacterium. We find that the flagellum exhibits a number of distinct dynamical states and comprehensively summarize them in a state diagram. As a result, we conclude that tuning the landscape of the extended Kirchhoff free energy alone cannot generate the intermediate full-length semicoiled state. However, our model suggests an ad hoc method to realize the sequence of polymorphic states as observed for a real bacterium. Since the elastic properties of bacterial flagella are similar, our findings can easily be extended to other peritrichous bacteria. PMID:27265475

  14. Ultrasonic Study of Crack Under a Dynamic Thermal Load

    SciTech Connect

    Pitkaenen, J.; Kemppainen, M.; Virkkunen, I.

    2004-02-26

    In piping the defects play a key role for determining the life of component. Also the risk for pipe failure combined to the defects has to be taken into account. In this study thermal dynamic load has been applied to austenitic material (AISI 304) in order to introduce dynamic behaviour into the crack. The studied crack ({approx}20 mm x 7 mm) has been produced by thermal fatigue in advance. Different ultrasonic techniques were used to reveal information from interaction of ultrasonic waves from dynamic behaviour of a crack face in the sonified volume. The ultrasonic probes in the study are typical probes for defect detection and sizing on site inspections This information helps us to understand some effects in nuclear piping such as detection of cracks with special techniques and difficulties in sizing of the cracks in real situations. In this case the material is loaded to exceed the yield strength. The thermal cycles used caused high variations in the temperature scale from 20 deg. C (68 F) to 600 deg. C (1112 F) in the crack volume especially on the crack surface area. These factors cause large stress variations in the vicinity of the crack. Effects which have been detected during analysis from the measurements explain well difficulties in ultrasonic inspections of those materials on site. Experimental work explains reasons why some defects are missed in the real piping. Ultrasonic techniques used are described in details and conclusion for applicability of those techniques has been drawn.

  15. Ultrasonic Study of Crack Under a Dynamic Thermal Load

    NASA Astrophysics Data System (ADS)

    Pitkänen, J.; Kemppainen, M.; Virkkunen, I.

    2004-02-01

    In piping the defects play a key role for determining the life of component. Also the risk for pipe failure combined to the defects has to be taken into account. In this study thermal dynamic load has been applied to austenitic material (AISI 304) in order to introduce dynamic behaviour into the crack. The studied crack (˜20 mm × 7 mm) has been produced by thermal fatigue in advance. Different ultrasonic techniques were used to reveal information from interaction of ultrasonic waves from dynamic behaviour of a crack face in the sonified volume. The ultrasonic probes in the study are typical probes for defect detection and sizing on site inspections This information helps us to understand some effects in nuclear piping such as detection of cracks with special techniques and difficulties in sizing of the cracks in real situations. In this case the material is loaded to exceed the yield strength. The thermal cycles used caused high variations in the temperature scale from 20°C (68 F) to 600°C (1112 F) in the crack volume especially on the crack surface area. These factors cause large stress variations in the vicinity of the crack. Effects which have been detected during analysis from the measurements explain well difficulties in ultrasonic inspections of those materials on site. Experimental work explains reasons why some defects are missed in the real piping. Ultrasonic techniques used are described in details and conclusion for applicability of those techniques has been drawn.

  16. Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers.

    PubMed

    Xiong, Yi; Zhu, Ji-Xiang; Fang, Zheng-Yu; Zeng, Cheng-Guang; Zhang, Chao; Qi, Guo-Long; Li, Man-Hui; Zhang, Wei; Quan, Da-Ping; Wan, Jun

    2012-01-01

    Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury. PMID:22619535

  17. Dynamical Models for Sloshing Dynamics of Helium 2 Under Low-G Conditions

    NASA Technical Reports Server (NTRS)

    Hung, R. J.; Long, Y. T.

    1997-01-01

    Coupling of sloshing dynamics within a partially filled rotating dewar of superfluid helium 2 with spacecraft dynamics are investigated in response to the realistic environmental disturbance forces and torques acting on the spacecraft during normal operation. This study investigates: (1) the rotating bubble of superfluid helium 2 reacting to combined environmental disturbances, including gravity gradient, aerodynamic, and magnetic forces and torques; (2) characteristics of slosh reaction forces and torques coupling with spacecraft dynamics; (3) the contribution of slosh dynamics to over-all spacecraft dynamics; and (4) activating of attitude and translation control system. The numerical computation of sloshing dynamics is based on the rotational frame, while the spacecraft dynamics is associated with non-rotational frame. Results show that the contributions of spacecraft dynamics are driven by the environmental disturbances coupling with slosh dynamics. Without considering the effects of environmental disturbances-driven slosh dynamics acting on spacecraft coupling with the spacecraft dynamics may lead to the wrong results for the development of spacecraft system guidance and attitude control techniques.

  18. Changing growth of neurites of sensory ganglion by terahertz radiation

    NASA Astrophysics Data System (ADS)

    Tsurkan, M. V.; Smolyanskaya, O. A.; Bespalov, V. G.; Penniyainen, V. A.; Kipenko, A. V.; Lopatina, E. V.; Krylov, B. V.

    2012-02-01

    Application of terahertz radiation for the creation of medical equipment and solving of biological problems has become widely spread. From this point of view, the influence of THz radiation on the nerve fibers is of primary concern. In addition, several studies indicated both stimulating and depressive effects on nerve cells. However, the mechanism of this effect has not yet been studied, including the dose and exposure time. Our research was devoted to the impact of broadband pulsed THz radiation in the frequency range of 0.05 to 2 THz on the neurite growth in the sensory ganglia of 10-12-day chicken embryos. Dependence of changes in functional responses of cells on the average output power has been found. An increase in the stimulating effect was observed at the lowest power density used (0.5 μW/cm2). Through non-destructive process and choosing the correct parameters of THz radiation, potential control of neural response becomes possible, which can subsequently lead to new medical treatments.

  19. Effects of fundamental structure parameters on dynamic responses of submerged floating tunnel under hydrodynamic loads

    NASA Astrophysics Data System (ADS)

    Long, Xu; Ge, Fei; Wang, Lei; Hong, Youshi

    2009-06-01

    This paper investigates the effects of structure parameters on dynamic responses of submerged floating tunnel (SFT) under hydrodynamic loads. The structure parameters includes buoyancy-weight ratio (BWR), stiffness coefficients of the cable systems, tunnel net buoyancy and tunnel length. First, the importance of structural damp in relation to the dynamic responses of SFT is demonstrated and the mechanism of structural damp effect is discussed. Thereafter, the fundamental structure parameters are investigated through the analysis of SFT dynamic responses under hydrodynamic loads. The results indicate that the BWR of SFT is a key structure parameter. When BWR is 1.2, there is a remarkable trend change in the vertical dynamic response of SFT under hydrodynamic loads. The results also indicate that the ratio of the tunnel net buoyancy to the cable stiffness coefficient is not a characteristic factor affecting the dynamic responses of SFT under hydrodynamic loads.

  20. On learning dynamics underlying the evolution of learning rules.

    PubMed

    Dridi, Slimane; Lehmann, Laurent

    2014-02-01

    In order to understand the development of non-genetically encoded actions during an animal's lifespan, it is necessary to analyze the dynamics and evolution of learning rules producing behavior. Owing to the intrinsic stochastic and frequency-dependent nature of learning dynamics, these rules are often studied in evolutionary biology via agent-based computer simulations. In this paper, we show that stochastic approximation theory can help to qualitatively understand learning dynamics and formulate analytical models for the evolution of learning rules. We consider a population of individuals repeatedly interacting during their lifespan, and where the stage game faced by the individuals fluctuates according to an environmental stochastic process. Individuals adjust their behavioral actions according to learning rules belonging to the class of experience-weighted attraction learning mechanisms, which includes standard reinforcement and Bayesian learning as special cases. We use stochastic approximation theory in order to derive differential equations governing action play probabilities, which turn out to have qualitative features of mutator-selection equations. We then perform agent-based simulations to find the conditions where the deterministic approximation is closest to the original stochastic learning process for standard 2-action 2-player fluctuating games, where interaction between learning rules and preference reversal may occur. Finally, we analyze a simplified model for the evolution of learning in a producer-scrounger game, which shows that the exploration rate can interact in a non-intuitive way with other features of co-evolving learning rules. Overall, our analyses illustrate the usefulness of applying stochastic approximation theory in the study of animal learning. PMID:24055617

  1. Antijamming technique research in dynamic stress test under random loading

    NASA Astrophysics Data System (ADS)

    Wang, Wenjing; Liu, Zhiming; Li, Qiang; Shen, Yanpeng

    2002-05-01

    Anti-jamming techniques were studied in dynamic stress test on bogie structure form the hardware and software. The paper sums up the hardware techniques like compound protection technique and anti-radiation jamming technique; and mainly introduces the software techniques such as zero drift signal processing, digital signal filtering processing, and wavelet signal processing. Additionally, an algorithm 'three-peak-valley stress value compare' is proposed in the wavelet signal processing. The results in application prove these measurements help to provide valid and reliable stress-time history signals for programming the bogie stress spectrum.

  2. Binary dynamics on star networks under external perturbations.

    PubMed

    Moreira, Carolina A; Schneider, David M; de Aguiar, Marcus A M

    2015-10-01

    We study a binary dynamical process that is a representation of the voter model with two candidates and opinion makers. The voters are represented by nodes of a network of social contacts with internal states labeled 0 or 1 and nodes that are connected can influence each other. The network is also perturbed by opinion makers, a set of external nodes whose states are frozen in 0 or 1 and that can influence all nodes of the network. The quantity of interest is the probability of finding m nodes in state 1 at time t. Here we study this process on star networks, which are simple representations of hubs found in complex systems, and compare the results with those obtained for networks that are fully connected. In both cases a transition from disordered to ordered equilibrium states is observed as the number of external nodes becomes small. For fully connected networks the probability distribution becomes uniform at the critical point. For star networks, on the other hand, we show that the equilibrium distribution splits in two peaks, reflecting the two possible states of the central node. We obtain approximate analytical solutions for the equilibrium distribution that clarify the role of the central node in the process. We show that the network topology also affects the time scale of oscillations in single realizations of the dynamics, which are much faster for the star network. Finally, extending the analysis to two stars we compare our results with simulations in simple scale-free networks. PMID:26565294

  3. Dynamics of public opinion under the influence of epidemic spreading

    NASA Astrophysics Data System (ADS)

    Wu, Junhui; Ni, Shunjiang; Shen, Shifei

    2016-02-01

    In this paper, we propose a novel model with dynamically adjusted confidence level of others to investigate the propagation of public opinion on whether to buy chicken in the case of avian influenza infection in humans. We study how people adjust their confidence level in other people’s opinions according to their perceived infection risk and how the opinion evolution and epidemic spreading affect each other on different complex networks by taking into account the spreading feature of avian influenza, that is, only people who buy chicken are possible to be infected. The simulation results show that in a closed system, people who support buying chicken and people who are infected can achieve a dynamic balance after a few time-steps, and the final stable state is mainly dependent on the level of people’s risk perception, rather than the initial distribution of the different opinions. Our results imply that in the course of the epidemic spread, transparent and timely announcement of the number of infections and the risk of infection can help people take the right self-protection actions, and thus help control the spread of avian influenza.

  4. Binary dynamics on star networks under external perturbations

    NASA Astrophysics Data System (ADS)

    Moreira, Carolina A.; Schneider, David M.; de Aguiar, Marcus A. M.

    2015-10-01

    We study a binary dynamical process that is a representation of the voter model with two candidates and opinion makers. The voters are represented by nodes of a network of social contacts with internal states labeled 0 or 1 and nodes that are connected can influence each other. The network is also perturbed by opinion makers, a set of external nodes whose states are frozen in 0 or 1 and that can influence all nodes of the network. The quantity of interest is the probability of finding m nodes in state 1 at time t . Here we study this process on star networks, which are simple representations of hubs found in complex systems, and compare the results with those obtained for networks that are fully connected. In both cases a transition from disordered to ordered equilibrium states is observed as the number of external nodes becomes small. For fully connected networks the probability distribution becomes uniform at the critical point. For star networks, on the other hand, we show that the equilibrium distribution splits in two peaks, reflecting the two possible states of the central node. We obtain approximate analytical solutions for the equilibrium distribution that clarify the role of the central node in the process. We show that the network topology also affects the time scale of oscillations in single realizations of the dynamics, which are much faster for the star network. Finally, extending the analysis to two stars we compare our results with simulations in simple scale-free networks.

  5. Dynamics of Nano-Confined Water under Pressure

    SciTech Connect

    Omar Diallo, Souleymane; Jazdzewska, Monika; Palmer, Jeremy; Mamontov, Eugene; Gubbins, Dr. K. E.; Sliwinska-Bartkowiak, M

    2013-01-01

    We report a study of the effects of pressure on the diffusivity of water molecules confined in single- wall carbon nanotubes (SWNT) with average mean pore diameter of 16 A. The measurements were carried out using high-resolution neutron scattering, over the temperature range 220 T 260 K, and at two pressure conditions: ambient and elevated pressure. The high pressure data were collected at constant volume on cooling, with P varying from 1.92 kbar at temperature T = 260 K to 1.85 kbar at T = 220 K. Analysis of the observed dynamic structure factor S(Q, E) reveals the presence of two relaxation processes, a faster diffusion component (FC) associated with the motion of caged or restricted molecules, and a slower component arising from the free water molecules diffusing within the SWNT matrix. While the temperature dependence of the slow relaxation time exhibits a Vogel-Fulcher-Tammann law and is non-Arrhenius in nature, the faster component follows an Arrhenius exponential law at both pressure conditions. The application of pressure remarkably slows down the overall molecular dynamics, in agreement with previous observations, but most notably affects the slow relaxation. The faster relaxation shows marginal or no change with pressure within the experimental conditions.

  6. Dynamic surface tension of natural surfactant extract under superimposed oscillations.

    PubMed

    Reddy, Prasika I; Al-Jumaily, Ahmed M; Bold, Geoff T

    2011-01-01

    Surfactant dysfunction plays a major role in respiratory distress syndrome (RDS). This research seeks to determine whether the use of natural surfactant, Curosurf™ (Cheisi Farmaceutici, Parma, Italy), accompanied with pressure oscillations at the level of the alveoli can reduce the surface tension in the lung, thereby making it easier for infants with RDS to maintain the required level of functional residual capacity (FRC) without collapse. To simulate the alveolar environment, dynamic surface tension measurements were performed on a modified pulsating bubble surfactometer (PBS) type device and showed that introducing superimposed oscillations about the tidal volume excursion between 10 and 70 Hz in a surfactant bubble lowers interfacial surface tension below values observed using tidal volume excursion alone. The specific mechanisms responsible for this improvement are yet to be established; however it is believed that one mechanism may be the rapid transient changes in the interfacial area increase the number of interfacial binding sites for surfactant molecules, increasing adsorption and diffusion to the interface, thereby decreasing interfacial surface tension. Existing mathematical models in the literature reproduce trends noticed in experiments in the range of breathing frequencies only. Thus, a modification is introduced to an existing model to both incorporate superimposed pressure oscillations and demonstrate that these may improve the dynamic surface tension in the alveoli. PMID:20883997

  7. Dynamical Response of Networks Under External Perturbations: Exact Results

    NASA Astrophysics Data System (ADS)

    Chinellato, David D.; Epstein, Irving R.; Braha, Dan; Bar-Yam, Yaneer; de Aguiar, Marcus A. M.

    2015-04-01

    We give exact statistical distributions for the dynamic response of influence networks subjected to external perturbations. We consider networks whose nodes have two internal states labeled 0 and 1. We let nodes be frozen in state 0, in state 1, and the remaining nodes change by adopting the state of a connected node with a fixed probability per time step. The frozen nodes can be interpreted as external perturbations to the subnetwork of free nodes. Analytically extending and to be smaller than 1 enables modeling the case of weak coupling. We solve the dynamical equations exactly for fully connected networks, obtaining the equilibrium distribution, transition probabilities between any two states and the characteristic time to equilibration. Our exact results are excellent approximations for other topologies, including random, regular lattice, scale-free and small world networks, when the numbers of fixed nodes are adjusted to take account of the effect of topology on coupling to the environment. This model can describe a variety of complex systems, from magnetic spins to social networks to population genetics, and was recently applied as a framework for early warning signals for real-world self-organized economic market crises.

  8. Dynamics of sex ratio and female unmatedness under haplodiploidy

    PubMed Central

    Gardner, Andy

    2014-01-01

    Haplodiploid sex determination allows unmated females to produce sons. Consequently, a scarcity of males may lead to a significant proportion of females remaining unmated, which may in turn give rise to a surfeit of males in the following generation. Stable oscillation of the sex ratio has been predicted by classic models, and it remains a puzzle as to why this is not observed in natural populations. Here, I investigate the dynamics of sex allocation over ecological and evolutionary timescales to assess the potential for sustained oscillation. I find that, whilst stable oscillation of the sex ratio is possible, the scope for such dynamical behavior is reduced if sex allocation strategies are evolutionary labile, especially if mated females may facultatively adjust their sex allocation according to the present availability of mating partners. My model, taken together with empirical estimates of female unmatedness in haplodiploid taxa, suggests that sustained oscillation of the sex ratio is implausible in natural populations. However, this phenomenon may be relevant to artificially introduced biological control agents. PMID:24967080

  9. Dynamics of drop coalescence on under-liquid substrates

    NASA Astrophysics Data System (ADS)

    Mitra, Surjyasish; Mitra, Sushanta

    2015-11-01

    Theoretical understanding of drop coalescence on under-liquid substrates is a challenging problem due to the presence of a surrounding viscous medium. Though, most work till date have focused on coalescence in air medium, the presence of a surrounding viscous medium is a significant extension to this classical coalescence problem. Such instances are often found in physical systems such as oil-spills, wetting of marine ecosystem, etc. In the present work, a modified one-dimensional lubrication equation has been developed to describe the early coalescence behavior of two symmetric sessile drops for under-liquid substrates, which takes into account the viscosities of both the drop and the surrounding medium. We found a new time scale which governs the process and there exist a cross-over time between the universal scaling of the bridge height growth \\hcirc ~ \\tcirc (valid for both under-liquid and air) and a much slower bridge growth \\hcirc ~\\tcirc 0 . 24 occurring at a later time. It is also found that the evolving bridge profile has a self-similarity, which breaks up much earlier for under-liquid substrates as opposed to symmetric coalescence in air.

  10. Optimal Dynamic Advertising Strategy Under Age-Specific Market Segmentation

    NASA Astrophysics Data System (ADS)

    Krastev, Vladimir

    2011-12-01

    We consider the model proposed by Faggian and Grosset for determining the advertising efforts and goodwill in the long run of a company under age segmentation of consumers. Reducing this model to optimal control sub problems we find the optimal advertising strategy and goodwill.

  11. Core Formation Under Dynamic Conditions: Physical Processes and Geochemical Signatures

    NASA Technical Reports Server (NTRS)

    Rushmer, T.; Gaetani, G.; Jones, J. H.; Sparks, J.

    2001-01-01

    We have experimentally investigated liquid metal segregation from a solid silicate matrix under conditions of applied stress. Liquid moves in fractures and formation of fayalitic olivine from orthopyroxene by migrating Fe-Ni-S-O liquids is observed. Additional information is contained in the original extended abstract.

  12. Water use dynamics of peach trees under postharvest deficit irrigation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Postharvest deficit irrigation is a potential strategy for conserving valuable fresh water for production of early season tree fruit crops such as peaches. However, behaviors of evapotranspiration characteristics and crop coefficient (Kc) under deficit irrigation conditions are largely unknown. A th...

  13. Specificity of prenatal cocaine on inhibition of locus coeruleus neurite outgrowth.

    PubMed

    Dey, S; Mactutus, C F; Booze, R M; Snow, D M

    2006-01-01

    Prenatal cocaine exposure induces alterations in attentional function that presumably involve locus coeruleus noradrenergic neurons and their projections. Previous reports indicate that embryonic rat locus coeruleus neurons exposed to cocaine, both in vitro and in vivo, showed in decreased cell survival and inhibition of neurite outgrowth, and that the effects were most deleterious during early gestation. The present study performed in vitro addressed the specificity of the inhibitory effects of cocaine by comparing locus coeruleus neurite formation and extension to that of dopaminergic substantia nigra neurons following exposure to a physiologically-relevant dose of cocaine (500 ng/ml, two times a day, for four days) during peak neuritogenesis. Following cocaine treatment, immunocytochemistry (anti-norepinephrine antibody to locus coeruleus; anti-tyrosine hydroxylase antibody to substantia nigra) and image analysis were performed to measure a variety of neurite outgrowth parameters. For locus coeruleus neurons, cocaine treatment decreased the 1) number of cells initiating neurites [P<0.001], 2) mean number [P<0.05] and length of neurites [P<0.0001], 3) mean number [P<0.0016] and length of branched neurites [P<0.0006], and 4) mean length of the longest neurites [P<0.0001]. In comparison, substantia nigra neurons were not significantly affected by cocaine for any of the parameters examined. More importantly, a significant interaction between cocaine treatment and brain region was observed [P<0.0002] indicating greater vulnerability of locus coeruleus, relative to substantia nigra neurons, to cocaine exposure. These data support our hypothesis that cocaine targets the noradrenergic system by negatively regulating locus coeruleus neuronal outgrowth, which likely affects pathfinding, synaptic connectivity, and ultimately attentional behavior in cocaine-exposed offspring. PMID:16483722

  14. Electrical and Neurotrophin Enhancement of Neurite Outgrowth within a 3D Collagen Scaffold

    PubMed Central

    Adams, Robert D.; Rendell, Sara R.; Counts, Lauren R.; Papke, Jason B.; Willits, Rebecca K.; Harkins, Amy B.

    2016-01-01

    Electrical and chemical stimulation have been studied as potent mechanisms of enhancing nerve regeneration and wound healing. However, it remains unclear how electrical stimuli affect nerve growth, particularly in the presence of neurotrophic factors. The objective of this study was to explore (1) the effect of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) supplementation to support neurite outgrowth in a 3D scaffold, and (2) the effect of brief, low voltage, electrical stimulation (ES) on neurite outgrowth prior to neurotrophin supplementation. Dissociated E11 chick dorsal root ganglia (DRG) were seeded within a 1.5 mg/mL type-I collagen scaffold. For neurotrophin treatments, scaffolds were incubated for 24 hrs in culture media containing nerve growth factor (NGF, 10 ng/mL) or BDNF (200 ng/mL), or both. For ES groups, scaffolds containing neurons were stimulated for 10 min at 8–10 V/m DC, then incubated for 24 hrs with neurotrophin. Fixed and labeled neurons were imaged to measure neurite growth and directionality. BDNF supplementation was not as effective as NGF at supporting DRG neurite outgrowth. ES prior to NGF supplementation improved DRG neurite outgrowth compared to NGF alone. This combination of brief ES with NGF treatment was the most effective treatment compared to NGF or BDNF alone. Brief ES had no impact on neurite directionality in the 3D scaffolds. These results demonstrate that ES improves neurite outgrowth in the presence of neurotrophins, and could provide a potential therapeutic approach to improve nerve regeneration when coupled with neurotrophin treatment. PMID:24710795

  15. Dynamic shear of granular material under variable gravity conditions

    NASA Technical Reports Server (NTRS)

    White, B. R.; Klein, S. P.

    1988-01-01

    This paper describes some experiments with granular materials which recently have been conducted aboard the NASA KC-135 aircraft during variable gravity maneuvers. The main experimental apparatus consisted of a small drum containing granular material which was rotated slowly while the angle assumed by the slip surface with respect to the horizontal was observed and recorded photographically. Conventional wisdom has held that this 'dynamic angle of response' was a material constant, independent of (among other things) gravitational level. The results presented here are quite contrary, suggesting instead an angle that varies with the reciprocal of the square root of gravity. This finding may have important consequences on the understanding of many active processes in Planetary Geology involving granular materials and may provide qualitative confirmation of some of the theoretical predictions of modern models of granular shear flows.

  16. DYNAMICS OF CHROMOSPHERIC UPFLOWS AND UNDERLYING MAGNETIC FIELDS

    SciTech Connect

    Yurchyshyn, V.; Abramenko, V.; Goode, P.

    2013-04-10

    We used H{alpha}-0.1 nm and magnetic field (at 1.56{mu}) data obtained with the New Solar Telescope to study the origin of the disk counterparts to type II spicules, so-called rapid blueshifted excursions (RBEs). The high time cadence of our chromospheric (10 s) and magnetic field (45 s) data allowed us to generate x-t plots using slits parallel to the spines of the RBEs. These plots, along with potential field extrapolation, led us to suggest that the occurrence of RBEs is generally correlated with the appearance of new, mixed, or unipolar fields in close proximity to network fields. RBEs show a tendency to occur at the interface between large-scale fields and small-scale dynamic magnetic loops and thus are likely to be associated with the existence of a magnetic canopy. Detection of kinked and/or inverse {sup Y-}shaped RBEs further confirm this conclusion.

  17. Orientational dynamics of nematic liquid crystals under shear flow

    NASA Astrophysics Data System (ADS)

    Rienäcker, G.; Hess, S.

    The orientational dynamics of low molecular weight and polymeric nematic liquid crystals in a flow field is investigated, based on a nonlinear relaxation equation for the second rank alignment tensor. Various approximations are discussed: Assuming uniaxial alignment with a constant order parameter, the results of the Ericksen-Leslie theory are recovered. The detailed analysis to be presented here for plane Couette flow concerns (i) uniaxial alignment with a variable degree of order and (ii) the tensorial analysis involving the three symmetry-adapted components of the five components of the alignment tensor. The transitions between tumbling, wagging and aligning behavior observed in polymeric liquid crystals and described by the Doi theory of rod-like nematic polymers are recovered. Consequences for the rheological behavior are indicated.

  18. The unique dynamical system underlying RR Lyrae pulsations

    NASA Astrophysics Data System (ADS)

    Kollath, Z.

    2016-05-01

    Hydrodynamic models of RR Lyrae pulsation display a very rich behaviour. Contrary to earlier expectations, high order resonances play a crucial role in the nonlinear dynamics representing the interacting modes. Chaotic attractors can be found at different time scales: both in the pulsation itself and in the amplitude equations shaping the possible modulation of the oscillations. Although there is no one-to-one connection between the nonlinear features found in the numerical models and the observed behaviour, the richness of the found phenomena suggests that the interaction of modes should be taken seriously in the study of the still unsolved puzzle of Blazhko effect. One of the main lessons of this complex system is that we should rethink the simple interpretation of the observed effect of resonances.

  19. Fundamental studies on the Cs dynamics under ion source conditions

    SciTech Connect

    Friedl, R. Fantz, U.

    2014-02-15

    The performance of surface conversion based negative hydrogen ion sources is mainly determined by the caesium dynamics. Therefore, fundamental investigations in vacuum and plasma are performed at a flexible laboratory setup with ion source parameters. Studies on the influence of Cs on the plasma parameters of H{sub 2} and D{sub 2} plasmas showed that n{sub e} and T{sub e} in the bulk plasma are not affected by relevant amounts of Cs and no isotopic differences could be observed. The coating of the vessel surfaces with Cs, however, leads to a considerable gettering of hydrogen atoms from the plasma volume and to the decrease of n{sub e} close to a sample surface due to the formation of negative ions.

  20. Dynamic response of shear thickening fluid under laser induced shock

    SciTech Connect

    Wu, Xianqian Yin, Qiuyun; Huang, Chenguang; Zhong, Fachun

    2015-02-16

    The dynamic response of the 57 vol./vol. % dense spherical silica particle-polyethylene glycol suspension at high pressure was investigated through short pulsed laser induced shock experiments. The measured back free surface velocities by a photonic Doppler velocimetry showed that the shock and the particle velocities decreased while the shock wave transmitted in the shear thickening fluid (STF), from which an equation of state for the STF was obtained. In addition, the peak stress decreased and the absorbed energy increased rapidly with increasing the thickness for a thin layer of the STF, which should be attributed to the impact-jammed behavior through compression of particle matrix, the deformation or crack of the hard-sphere particles, and the volume compression of the particles and the polyethylene glycol.

  1. The cortical dynamics underlying effective switching of auditory spatial attention

    PubMed Central

    Larson, Eric; Lee, Adrian KC

    2012-01-01

    Successful rapid deployment of attention to relevant sensory stimuli is critical for survival. In a complex environment, attention can be captured by salient events or be deployed volitionally. Furthermore, when multiple events are of interest concurrently, effective interaction with one's surroundings hinges on efficient top-down control of shifting attention. It has been hypothesized that two separate cortical networks coordinate attention shifts across multiple modalities. However, the cortical dynamics of these networks and their behavioral relevance to switching of auditory attention are unknown. Here we show that the strength of each subject's right temporal-parietal junction (RTPJ, part of the ventral network) activation was highly correlated with their behavioral performance in an auditory task. We also provide evidence that the recruitment of the RTPJ likely precedes the right frontal eye fields (FEF; participating in both the dorsal and ventral networks) and middle frontal gyrus (MFG) by around 100 ms when subjects switch their auditory spatial attention. PMID:22974974

  2. Dynamics of a nanodroplet under a transmission electron microscope

    SciTech Connect

    Leong, Fong Yew; Mirsaidov, Utkur M.; Matsudaira, Paul; Mahadevan, L.

    2014-01-15

    We investigate the cyclical stick-slip motion of water nanodroplets on a hydrophilic substrate viewed with and stimulated by a transmission electron microscope. Using a continuum long wave theory, we show how the electrostatic stress imposed by non-uniform charge distribution causes a pinned convex drop to deform into a toroidal shape, with the shape characterized by the competition between the electrostatic stress and the surface tension of the drop, as well as the charge density distribution which follows a Poisson equation. A horizontal gradient in the charge density creates a lateral driving force, which when sufficiently large, overcomes the pinning induced by surface heterogeneities in the substrate disjoining pressure, causing the drop to slide on the substrate via a cyclical stick-slip motion. Our model predicts step-like dynamics in drop displacement and surface area jumps, qualitatively consistent with experimental observations.

  3. Microstructural Effects on Materials under Extreme Dynamic Environments

    NASA Astrophysics Data System (ADS)

    Williams, Cyril

    Studies have shown that microstructure and microstructure evolution can play a major role on the shock response of metals and metallic alloys. When metals and metallic alloys are deformed during shock compression, large numbers of lattice defects such as dislocations can be introduced in the material. These dislocations can lead to strengthening effects such as hardening and/or softening such as dynamic recovery which may consequently change the material behavior. Therefore, to better understand the effects of microstructure and microstructure evolution on the spall response of metals, both in-situ and end-state gas gun plate impact experiments were employed to study 1100-O aluminum. The results show a sharp increase in pullback velocity for 1100-O aluminum with increase in peak shock stress between 4.0 and 8.3 GPa due to shock hardening, followed by a decrease for peak shock stresses up to 12.0 GPa due to softening induced by dynamic recovery. addition, the effects of microstructure on the spall properties of two magnesium alloys fabricated via ECAE (AZ31B-4E) and SWAP (AMX602) were also investigated. The pullback velocities were found to decrease by approximately 15% for AZ31B-4E between 1.7 GPa to 4.6 GPa shock stress. On the contrary, the pullback velocities for AMX602 were found to be random for the same shock stress range studied. Residual microstructure of the post-shocked AZ31B-4E magnesium shows that aluminum-manganese intermetallic inclusions were perhaps responsible for the reduction in pullback velocity. Also, the post-shocked residual microstructure of the AMX602 magnesium revealed features that may have been responsible for its random response.

  4. Soap film dynamics and topological jumps under continuous deformation

    NASA Astrophysics Data System (ADS)

    Moffatt, Keith

    2015-11-01

    Consider the dynamics of a soap-film bounded by a flexible wire (or wires) which can be continuously and slowly deformed. At each instant the soap-film relaxes in quasi-static manner to a minimum-area (i.e. minimum-energy) state compatible with the boundary configuration. This can however pass through a critical configuration at which a topological jump is inevitable. We have studied an interesting example of this behaviour: the jump of a one-sided (Möbius strip) soap-film to a two-sided film as the boundary is unfolded and untwisted from the double cover of a circle. The nature of this jump will be demonstrated and explained. More generally, dynamical systems have a natural tendency to relax through dissipative processes to a minimum-energy state, subject to any relevant constraints. An example is provided by the relaxation of a magnetic field in a perfectly conducting but viscous fluid, subject to the constraint that the magnetic field lines are frozen in the fluid. One may infer the existence of magnetostatic equilibria (and analogous steady Euler flows) of arbitrary field-line topology. In general, discontinuities (current sheets) appear during this relaxation process, and this is where reconnection of field-lines (with associated change of topology) can occur. Just as for the soap film, slow change of boundary conditions can lead to critical conditions in which such topological jumps are inevitable. (Work in collaboration with Ray Goldstein, Adriana Pesci, Renzo Ricca and Gareth Alexander.) This work was supported by Engineering and Physical Sciences Research Council Grant EP/I036060/1.

  5. Centrosome movements in vivo correlate with specific neurite formation downstream of LIM homeodomain transcription factor activity.

    PubMed

    Andersen, Erica F; Halloran, Mary C

    2012-10-01

    Neurons must develop complex structure to form proper connections in the nervous system. The initiation of axons in defined locations on the cell body and their extension to synaptic targets are critical steps in neuronal morphogenesis, yet the mechanisms controlling axon formation in vivo are poorly understood. The centrosome has been implicated in multiple aspects of neuronal morphogenesis; however, its function in axon development is under debate. Conflicting results from studies of centrosome function in axonogenesis suggest that its role is context dependent and underscore the importance of studying centrosome function as neurons develop in their natural environment. Using live imaging of zebrafish Rohon-Beard (RB) sensory neurons in vivo, we discovered a spatiotemporal relationship between centrosome position and the formation of RB peripheral, but not central, axons. We tested centrosome function by laser ablation and found that centrosome disruption inhibited peripheral axon outgrowth. In addition, we show that centrosome position and motility are regulated by LIM homeodomain transcription factor activity, which is specifically required for the development of RB peripheral axons. Furthermore, we show a correlation between centrosome mislocalization and ectopic axon formation in bashful (laminin alpha 1) mutants. Thus, both intrinsic transcription factor activity and extracellular cues can influence centrosome position and axon formation in vivo. This study presents the first positive association between the centrosome and axon formation in vivo and suggests that the centrosome is important for differential neurite formation in neurons with complex axonal morphologies. PMID:22899847

  6. Salubrinal inhibits the expression of proteoglycans and favors neurite outgrowth from cortical neurons in vitro.

    PubMed

    Barreda-Manso, M Asunción; Yanguas-Casás, Natalia; Nieto-Sampedro, Manuel; Romero-Ramírez, Lorenzo

    2015-07-01

    After CNS injury, astrocytes and mesenchymal cells attempt to restore the disrupted glia limitans by secreting proteoglycans and extracellular matrix proteins (ECMs), forming the so-called glial scar. Although the glial scar is important in sealing the lesion, it is also a physical and functional barrier that prevents axonal regeneration. The synthesis of secretory proteins in the RER is under the control of the initiation factor of translation eIF2α. Inhibiting the synthesis of secretory proteins by increasing the phosphorylation of eIF2α, might be a pharmacologically efficient way of reducing proteoglycans and other profibrotic proteins present in the glial scar. Salubrinal, a neuroprotective drug, decreased the expression and secretion of proteoglycans and other profibrotic proteins induced by EGF or TGFβ, maintaining eIF2α phosphorylated. Besides, Salubrinal also reduced the transcription of proteoglycans and other profibrotic proteins, suggesting that it induced the degradation of non-translated mRNA. In a model in vitro of the glial scar, cortical neurons grown on cocultures of astrocytes and fibroblasts with TGFβ treated with Salubrinal, showed increased neurite outgrowth compared to untreated cells. Our results suggest that Salubrinal may be considered of therapeutic value facilitating axonal regeneration, by reducing overproduction and secretion of proteoglycans and profibrotic protein inhibitors of axonal growth. PMID:25882497

  7. Leaf Dynamics of Panicum maximum under Future Climatic Changes.

    PubMed

    Britto de Assis Prado, Carlos Henrique; Haik Guedes de Camargo-Bortolin, Lívia; Castro, Érique; Martinez, Carlos Alberto

    2016-01-01

    Panicum maximum Jacq. 'Mombaça' (C4) was grown in field conditions with sufficient water and nutrients to examine the effects of warming and elevated CO2 concentrations during the winter. Plants were exposed to either the ambient temperature and regular atmospheric CO2 (Control); elevated CO2 (600 ppm, eC); canopy warming (+2°C above regular canopy temperature, eT); or elevated CO2 and canopy warming (eC+eT). The temperatures and CO2 in the field were controlled by temperature free-air controlled enhancement (T-FACE) and mini free-air CO2 enrichment (miniFACE) facilities. The most green, expanding, and expanded leaves and the highest leaf appearance rate (LAR, leaves day(-1)) and leaf elongation rate (LER, cm day(-1)) were observed under eT. Leaf area and leaf biomass were higher in the eT and eC+eT treatments. The higher LER and LAR without significant differences in the number of senescent leaves could explain why tillers had higher foliage area and leaf biomass in the eT treatment. The eC treatment had the lowest LER and the fewest expanded and green leaves, similar to Control. The inhibitory effect of eC on foliage development in winter was indicated by the fewer green, expanded, and expanding leaves under eC+eT than eT. The stimulatory and inhibitory effects of the eT and eC treatments, respectively, on foliage raised and lowered, respectively, the foliar nitrogen concentration. The inhibition of foliage by eC was confirmed by the eC treatment having the lowest leaf/stem biomass ratio and by the change in leaf biomass-area relationships from linear or exponential growth to rectangular hyperbolic growth under eC. Besides, eC+eT had a synergist effect, speeding up leaf maturation. Therefore, with sufficient water and nutrients in winter, the inhibitory effect of elevated CO2 on foliage could be partially offset by elevated temperatures and relatively high P. maximum foliage production could be achieved under future climatic change. PMID:26894932

  8. Leaf Dynamics of Panicum maximum under Future Climatic Changes

    PubMed Central

    Britto de Assis Prado, Carlos Henrique; Haik Guedes de Camargo-Bortolin, Lívia; Castro, Érique; Martinez, Carlos Alberto

    2016-01-01

    Panicum maximum Jacq. ‘Mombaça’ (C4) was grown in field conditions with sufficient water and nutrients to examine the effects of warming and elevated CO2 concentrations during the winter. Plants were exposed to either the ambient temperature and regular atmospheric CO2 (Control); elevated CO2 (600 ppm, eC); canopy warming (+2°C above regular canopy temperature, eT); or elevated CO2 and canopy warming (eC+eT). The temperatures and CO2 in the field were controlled by temperature free-air controlled enhancement (T-FACE) and mini free-air CO2 enrichment (miniFACE) facilities. The most green, expanding, and expanded leaves and the highest leaf appearance rate (LAR, leaves day-1) and leaf elongation rate (LER, cm day-1) were observed under eT. Leaf area and leaf biomass were higher in the eT and eC+eT treatments. The higher LER and LAR without significant differences in the number of senescent leaves could explain why tillers had higher foliage area and leaf biomass in the eT treatment. The eC treatment had the lowest LER and the fewest expanded and green leaves, similar to Control. The inhibitory effect of eC on foliage development in winter was indicated by the fewer green, expanded, and expanding leaves under eC+eT than eT. The stimulatory and inhibitory effects of the eT and eC treatments, respectively, on foliage raised and lowered, respectively, the foliar nitrogen concentration. The inhibition of foliage by eC was confirmed by the eC treatment having the lowest leaf/stem biomass ratio and by the change in leaf biomass-area relationships from linear or exponential growth to rectangular hyperbolic growth under eC. Besides, eC+eT had a synergist effect, speeding up leaf maturation. Therefore, with sufficient water and nutrients in winter, the inhibitory effect of elevated CO2 on foliage could be partially offset by elevated temperatures and relatively high P. maximum foliage production could be achieved under future climatic change. PMID:26894932

  9. Dynamic Void Growth and Shrinkage in Mg under Electron Irradiation

    SciTech Connect

    Xu, W. Z.; Zhang, Y. F.; Cheng, G. M.; Jian, W. W.; Millett, P. C.; Koch, C. C.; Mathaudhu, S. N.; Zhu, Y. T.

    2014-04-30

    We report in-situ atomic-scale investigation of void evolution, including growth, coalescence and shrinkage, under electron irradiation. With increasing irradiation dose, the total volume of voids increased linearly, while nucleation rate of new voids decreased slightly, and the total number of voids decreased. Some voids continued to grow while others shrank to disappear, depending on the nature of their interactions with nearby self-interstitial loops. For the first time, surface diffusion of adatoms was observed largely responsible for the void coalescence and thickening. These findings provide fundamental understanding to help with the design and modeling of irradiation-resistant materials.

  10. Beller Lectureship: Dynamics of skyrmions under electric current

    NASA Astrophysics Data System (ADS)

    Nagaosa, Naoto

    2013-03-01

    Current-driven motion of the skyrmions and skyrmion crystal is attracting intense attention because of the very small critical current density, but the microscopic mechanism of their motion is not yet explored. In this talk, I will present a numerical simulation of the Landau-Lifshitz-Gilbert (LLG) equation and an analytic theory, which reveals a remarkably robust and universal current-velocity relation of the skyrmion motion driven by the spin transfer torque unaffected by either impurities or nonadiabatic effect in sharp contrast to the case of domain wall or spin helix. This is due to the peculiar dynamics of skyrmions characterized by inherent absence of the intrinsic pinning and flexible shape-deformation of skyrmions so as to avoid pinning centers. The effect of the constricted geometry will be also discussed. This work has been done in collaboration with J. Iwasaki and M. Mochizuki. This work was supported by Grant-in-Aids for Scientific Research (No. 24224009) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST).

  11. Peru-Chile upwelling dynamics under climate change

    NASA Astrophysics Data System (ADS)

    Oerder, Véra; Colas, Francois; Echevin, Vincent; Codron, Francis; Tam, Jorge; Belmadani, Ali

    2015-02-01

    The consequences of global warming on the Peru-Chile Current System (PCCS) ocean circulation are examined with a high-resolution, eddy-resolving regional oceanic model. We performed a dynamical downscaling of climate scenarios from the IPSL-CM4 Coupled General Circulation Model (CGCM), corresponding to various levels of CO2 concentrations in the atmosphere. High-resolution atmospheric forcing for the regional ocean model are obtained from the IPSL atmospheric model run on a stretched grid with increased horizontal resolution in the PCCS region. When comparing future scenarios to preindustrial (PI) conditions, the circulation along the Peru and Chile coasts is strongly modified by changes in surface winds and increased stratification caused by the regional warming. While the coastal poleward undercurrent is intensified, the surface equatorial coastal jet shoals and the nearshore mesoscale activity are reinforced. Reduction in alongshore wind stress and nearshore wind stress curl drive a year-round reduction in upwelling intensity off Peru. Modifications in geostrophic circulation mitigate this upwelling decrease in late austral summer. The depth of the upwelling source waters becomes shallower in warmer conditions, which may have a major impact on the system's biological productivity.

  12. A Dynamic Search Process Underlies MicroRNA Targeting

    PubMed Central

    Chandradoss, Stanley D.; MacRae, Ian J.; Joo, Chirlmin

    2016-01-01

    Summary Argonaute proteins play a central role in mediating post-transcriptional gene regulation by microRNAs (miRNAs). Argonautes use the nucleotide sequences in miRNAs as guides for identifying target messenger RNAs for repression. Here we used single-molecule FRET to directly visualize how human Argonaute-2 (Ago2) searches for and identifies target sites in RNAs complementary to its miRNA guide. Our results suggest that Ago2 initially scans for target sites with complementarity to nucleotides 2–4 of the miRNA. This initial transient interaction propagates into a stable association when target complementarity extends to nucleotides 2–8. This stepwise recognition process is coupled to lateral diffusion of Ago2 along the target RNA, which promotes target search by enhancing the retention of Ago2 on the RNA. The combined results reveal the mechanisms that Argonaute likely uses to efficiently identify miRNA target sites within the vast and dynamic agglomeration of RNA molecules in the living cell. PMID:26140593

  13. Spatiotemporal dynamics of insect pest population under viral infection.

    PubMed

    Ghosh, Suma; Bhattacharyya, Samit

    2013-07-01

    The interrelationship between pathogen infection and host mobility is of great importance for successful spread of disease in spatial pest population. As spread of infection depends on horizontal transmission of pathogen, there are numerous factors like susceptibility, latent period, host movement that influence overall effectiveness of the control policy. Initiation of new infection cycle depends on density of infected inoculum in the site. So, spatial movement of infected hosts during the course of infection influence the dynamics. Also, infected individuals are more vulnerable to predators and hence production of virus particles in the site depends on predation to some extent. We derive a four dimensional delayed reaction-diffusion model in one spatial dimension and compute the minimum travelling speed of transmission of infection. We show that the minimum speed is sensitive to several parameters of the system. For example, the minimum speed decreases only with increase in delay in lysis process, but otherwise it increases with increase in force of infection, diffusivity of infectives or per capita virus production. A concluding discussion with numerical simulation is presented in the end. PMID:23562890

  14. A Dynamic Search Process Underlies MicroRNA Targeting.

    PubMed

    Chandradoss, Stanley D; Schirle, Nicole T; Szczepaniak, Malwina; MacRae, Ian J; Joo, Chirlmin

    2015-07-01

    Argonaute proteins play a central role in mediating post-transcriptional gene regulation by microRNAs (miRNAs). Argonautes use the nucleotide sequences in miRNAs as guides for identifying target messenger RNAs for repression. Here, we used single-molecule FRET to directly visualize how human Argonaute-2 (Ago2) searches for and identifies target sites in RNAs complementary to its miRNA guide. Our results suggest that Ago2 initially scans for target sites with complementarity to nucleotides 2-4 of the miRNA. This initial transient interaction propagates into a stable association when target complementarity extends to nucleotides 2-8. This stepwise recognition process is coupled to lateral diffusion of Ago2 along the target RNA, which promotes the target search by enhancing the retention of Ago2 on the RNA. The combined results reveal the mechanisms that Argonaute likely uses to efficiently identify miRNA target sites within the vast and dynamic agglomeration of RNA molecules in the living cell. PMID:26140593

  15. Polymer Brushes under Shear: Molecular Dynamics Simulations Compared to Experiments.

    PubMed

    Singh, Manjesh K; Ilg, Patrick; Espinosa-Marzal, Rosa M; Kröger, Martin; Spencer, Nicholas D

    2015-04-28

    Surfaces coated with polymer brushes in a good solvent are known to exhibit excellent tribological properties. We have performed coarse-grained equilibrium and nonequilibrium molecular dynamics (MD) simulations to investigate dextran polymer brushes in an aqueous environment in molecular detail. In a first step, we determined simulation parameters and units by matching experimental results for a single dextran chain. Analyzing this model when applied to a multichain system, density profiles of end-tethered polymer brushes obtained from equilibrium MD simulations compare very well with expectations based on self-consistent field theory. Simulation results were further validated against and correlated with available experimental results. The simulated compression curves (normal force as a function of surface separation) compare successfully with results obtained with a surface forces apparatus. Shear stress (friction) obtained via nonequilibrium MD is contrasted with nanoscale friction studies employing colloidal-probe lateral force microscopy. We find good agreement in the hydrodynamic regime and explain the observed leveling-off of the friction forces in the boundary regime by means of an effective polymer-wall attraction. PMID:25830715

  16. Phase Resetting Reveals Network Dynamics Underlying a Bacterial Cell Cycle

    PubMed Central

    Lin, Yihan; Li, Ying; Crosson, Sean; Dinner, Aaron R.; Scherer, Norbert F.

    2012-01-01

    Genomic and proteomic methods yield networks of biological regulatory interactions but do not provide direct insight into how those interactions are organized into functional modules, or how information flows from one module to another. In this work we introduce an approach that provides this complementary information and apply it to the bacterium Caulobacter crescentus, a paradigm for cell-cycle control. Operationally, we use an inducible promoter to express the essential transcriptional regulatory gene ctrA in a periodic, pulsed fashion. This chemical perturbation causes the population of cells to divide synchronously, and we use the resulting advance or delay of the division times of single cells to construct a phase resetting curve. We find that delay is strongly favored over advance. This finding is surprising since it does not follow from the temporal expression profile of CtrA and, in turn, simulations of existing network models. We propose a phenomenological model that suggests that the cell-cycle network comprises two distinct functional modules that oscillate autonomously and couple in a highly asymmetric fashion. These features collectively provide a new mechanism for tight temporal control of the cell cycle in C. crescentus. We discuss how the procedure can serve as the basis for a general approach for probing network dynamics, which we term chemical perturbation spectroscopy (CPS). PMID:23209388

  17. Fluctuation and dynamics of a lipid bilayer membrane under an electric field

    NASA Astrophysics Data System (ADS)

    Young, Yuan-Nan; Miksis, Michael; Vlahovska, Petia

    2015-11-01

    Membrane fluctuation and dynamics under an electric field is investigated, and results show that the membrane instability and dynamics depend not only on the mismatch in conductivity and permittivity between the bulk fluids, but also on the membrane charging time. In addition, the (entropic) membrane tension is found to depend on the electric field. Lubrication theory is utilized to examine the nonlinear dynamics of a planar lipid bilayer membrane with and without electrokinetics. Partial support from NSF/DMS 1222550, 1412789.

  18. Micropatterned coumarin polyester thin films direct neurite orientation.

    PubMed

    McCormick, Aleesha M; Maddipatla, Murthy V S N; Shi, Shuojia; Chamsaz, Elaheh A; Yokoyama, Hiroshi; Joy, Abraham; Leipzig, Nic D

    2014-11-26

    Guidance and migration of cells in the nervous system is imperative for proper development, maturation, and regeneration. In the peripheral nervous system (PNS), it is challenging for axons to bridge critical-sized injury defects to achieve repair and the central nervous system (CNS) has a very limited ability to regenerate after injury because of its innate injury response. The photoreactivity of the coumarin polyester used in this study enables efficient micropatterning using a custom digital micromirror device (DMD) and has been previously shown to be biodegradable, making these thin films ideal for cell guidance substrates with potential for future in vivo applications. With DMD, we fabricated coumarin polyester thin films into 10×20 μm and 15×50 μm micropatterns with depths ranging from 15 to 20 nm to enhance nervous system cell alignment. Adult primary neurons, oligodendrocytes, and astrocytes were isolated from rat brain tissue and seeded onto the polymer surfaces. After 24 h, cell type and neurite alignment were analyzed using phase contrast and fluorescence imaging. There was a significant difference (p<0.0001) in cell process distribution for both emergence angle (from the body of the cell) and orientation angle (at the tip of the growth cone) confirming alignment on patterned surfaces compared to control substrates (unpatterned polymer and glass surfaces). The expected frequency distribution for parallel alignment (≤15°) is 14% and the two micropatterned groups ranged from 42 to 49% alignment for emergence and orientation angle measurements, where the control groups range from 12 to 22% for parallel alignment. Despite depths being 15 to 20 nm, cell processes could sense these topographical changes and preferred to align to certain features of the micropatterns like the plateau/channel interface. As a result this initial study in utilizing these new DMD micropatterned coumarin polyester thin films has proven beneficial as an axon guidance platform

  19. Dopamine uptake dynamics are preserved under isoflurane anesthesia.

    PubMed

    Brodnik, Zachary D; España, Rodrigo A

    2015-10-01

    Fast scan cyclic voltammetry is commonly used for measuring the kinetics of dopamine release and uptake. For experiments using an anesthetized preparation, urethane is preferentially used because it does not alter dopamine uptake kinetics compared to freely moving animals. Unfortunately, urethane is highly toxic, can induce premature death during experiments, and cannot be used for recovery surgeries. Isoflurane is an alternative anesthetic that is less toxic than urethane, produces a stable level of anesthesia over extended periods, and is often used for recovery surgeries. Despite these benefits, the effects of isoflurane on dopamine release and uptake have not been directly characterized. In the present studies, we assessed the utility of isoflurane for voltammetry experiments by testing dopamine signaling parameters under baseline conditions, after treatment with the dopamine uptake inhibitor cocaine, and after exposure to increasing concentrations of isoflurane. Our results indicate that surgical levels of isoflurane do not significantly alter terminal mechanisms of dopamine release and uptake over prolonged periods of time. Consequently, we propose that isoflurane is an acceptable anesthetic for voltammetry experiments, which in turn permits the design of studies in which dopamine signaling is examined under anesthesia prior to recovery and subsequent experimentation in the same animals. PMID:26321152

  20. Eliminating Piezoresistivity in Flexible Conducting Polymers for Accurate Temperature Sensing under Dynamic Mechanical Deformations.

    PubMed

    Sezen, Melda; Register, Jeffrey T; Yao, Yao; Glisic, Branko; Loo, Yueh-Lin

    2016-06-01

    The polarity and the magnitude of polyaniline's gauge factor are tuned through structural modification. Combining conducting polymers with gauge factors of opposite polarities yields an accurate temperature sensor, even when deployed under dynamic strains. PMID:27061270

  1. Motor Coordination Dynamics Underlying Graphic Motion in 7- to 11-Year-Old Children

    ERIC Educational Resources Information Center

    Danna, Jeremy; Enderli, Fabienne; Athenes, Sylvie; Zanone, Pier-Giorgio

    2012-01-01

    Using concepts and tools of a dynamical system approach in order to understand motor coordination underlying graphomotor skills, the aim of the current study was to establish whether the basic coordination dynamics found in adults is already established in children at elementary school, when handwriting is trained and eventually acquired. In the…

  2. Pavarotti/MKLP1 regulates microtubule sliding and neurite outgrowth in Drosophila neurons

    PubMed Central

    del Castillo, Urko; Lu, Wen; Winding, Michael; Lakonishok, Margot; Gelfand, Vladimir I.

    2014-01-01

    Summary Recently, we demonstrated that kinesin-1 can slide microtubules against each other providing the mechanical force required for initial neurite extension in Drosophila neurons. This sliding is only observed in young neurons actively forming neurites and is dramatically downregulated in older neurons. The downregulation is not caused by the global shut-down of kinesin-1, as the ability of kinesin-1 to transport membrane organelles is not diminished in mature neurons, suggesting that microtubule sliding is regulated by a dedicated mechanism [1]. Here, we have identified the “mitotic” kinesin Pavarotti (Pav-KLP) as an inhibitor of kinesin-1-driven microtubule sliding. Depletion of Pav-KLP in neurons strongly stimulated the sliding of long microtubules and neurite outgrowth, while its ectopic overexpression in the cytoplasm blocked both of these processes. Furthermore, postmitotic depletion of Pav-KLP in Drosophila neurons in vivo reduced embryonic/larval viability, with only a few animals surviving to the third instar larval stage. A detailed examination of motor neurons in the surviving larvae revealed the overextension of axons and mistargeting of neuromuscular junctions, resulting in uncoordinated locomotion. Taken together, our results identify a new role for Pav-KLP as a negative regulator of kinesin-1 driven neurite formation. These data suggest an important parallel between long microtubule-microtubule sliding in anaphase B and sliding of interphase microtubules during neurite formation. PMID:25557664

  3. IL-1{beta} promotes neurite outgrowth by deactivating RhoA via p38 MAPK pathway

    SciTech Connect

    Temporin, Ko; Tanaka, Hiroyuki Kuroda, Yusuke; Okada, Kiyoshi; Yachi, Koji; Moritomo, Hisao; Murase, Tsuyoshi; Yoshikawa, Hideki

    2008-01-11

    Expression of the pro-inflammatory cytokine interleukin-1 beta (IL-1{beta}) is increased following the nervous system injury. Generally IL-1{beta} induces inflammation, leading to neural degeneration, while several neuropoietic effects have also been reported. Although neurite outgrowth is an important step in nerve regeneration, whether IL-1{beta} takes advantages on it is unclear. Now we examine how it affects neurite outgrowth. Following sciatic nerve injury, expression of IL-1{beta} is increased in Schwann cells around the site of injury, peaking 1 day after injury. In dorsal root ganglion (DRG) neurons and cerebellar granule neurons (CGNs), neurite outgrowth is inhibited by the addition of myelin-associated glycoprotein (MAG), activating RhoA. IL-1{beta} overcomes MAG-induced neurite outgrowth inhibition, by deactivating RhoA. Intracellular signaling experiments reveal that p38 MAPK, and not nuclear factor-kappa B (NF-{kappa}B), mediated this effect. These findings suggest that IL-1{beta} may contribute to nerve regeneration by promoting neurite outgrowth following nerve injury.

  4. Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status

    SciTech Connect

    Lu, Jiaqi; Cao, Yuanzhao; Cheng, Kuoyuan; Xu, Bo; Wang, Tianchang; Yang, Qi; Yang, Qin; Feng, Xudong; Xia, Qing

    2015-06-10

    As a widely used anti-bacterial agent and a metabolic inhibitor as well as AMP-activated protein kinase (AMPK) activator, berberine (BBR) has been shown to cross the blood–brain barrier. Its efficacy has been investigated in various disease models of the central nervous system. Neurite outgrowth is critical for nervous system development and is a highly energy-dependent process regulated by AMPK-related pathways. In the present study, we aimed to investigate the effects of BBR on AMPK activation and neurite outgrowth in neurons. The neurite outgrowth of primary rat cortical neurons at different stages of polarization was monitored after exposure of BBR. Intracellular energy level, AMPK activation and polarity-related pathways were also inspected. The results showed that BBR suppressed neurite outgrowth and affected cytoskeleton stability in the early stages of neuronal polarization, which was mediated by lowered energy status and AMPK activation. Liver kinase B1 and PI3K–Akt–GSK3β signaling pathways were also involved. In addition, mitochondrial dysfunction and endoplasmic reticulum stress contributed to the lowered energy status induced by BBR. This study highlighted the knowledge of the complex activities of BBR in neurons and corroborated the significance of energy status during the neuronal polarization. - Highlights: • BBR inhibited neurite outgrowth in early stages of neuronal development. • Lowered neuronal energy status was induced by BBR treatment. • Neuronal energy stress induced by BBR activated AMPK-related pathways. • BBR induced mitochondrial dysfunction and endoplasmic reticulum stress.

  5. Identification of molecules in leech extracellular matrix that promote neurite outgrowth.

    PubMed

    Masuda-Nakagawa, L; Beck, K; Chiquet, M

    1988-12-22

    The molecular composition of the substrate is of critical importance for neurite extension by isolated identified leech nerve cells in culture. One substrate upon which rapid growth occurs in defined medium is a cell-free extract of extracellular matrix (ECM) that surrounds the leech central nervous system (CNS). Here we report the co-purification of neurite-promoting activity with a laminin-like molecule. High molecular mass proteins from leech ECM purified by gel filtration exhibited increased specific activity for promoting neurite outgrowth. The most active fractions contained three major polypeptide bands of ca. 340, 250 and 220 kDa. Electron microscopy of rotary-shadowed samples showed three macromolecules, one of which had a cross-shaped structure similar to vertebrate laminin. A second six-armed molecule resembled vertebrate tenascin and a third rod-like molecule resembled vertebrate collagen type IV. The most active fractions contained a protein of ca. 1 MDa on non-reducing gels with disulphide-linked subunits of ca. 220 and 340 kDa, with cross-shaped laminin-like molecules. We conclude that a laminin-like molecule represents a major neurite promoting component present in leech ECM. The experiments represent a first step in determining the location of leech laminin within the CNS and assessing its role in neurite outgrowth during development and regeneration. PMID:2907383

  6. Neurite outgrowth and synapse formation by identified leech neurones in culture.

    PubMed

    Chiquet, M; Nicholls, J G

    1987-09-01

    After injury, neurones in the central nervous system (CNS) of the leech regenerate with a high degree of specificity. The aim of our experiments has been to study the sequential steps involved in neurite growth and synapse formation using isolated identified neurones in culture. An important requirement for sprouting of leech neurones is the substrate. Neurites grow only slowly and sparsely on polylysine or vertebrate laminin. The extracellular matrix of leech ganglion capsules contains a protease-sensitive factor which can be extracted with urea. With this material as substrate, growth proceeds rapidly in defined medium. Another neurite-promoting substrate is provided by the plant lectin concanavalin A (Con A). The activity of Con A, but not of the capsule matrix factor, is blocked by the Con A-specific hapten methyl alpha-D-mannoside. The morphology and branching pattern of the neurites in culture depend on the specific substrate and on the type of neurone. During stimulation, less Ca2+ uptake occurs into growth cones than in cell bodies. The mechanism of neurite growth seems not to depend on activity-mediated Ca2+ influx or on interactions between neuronal cell surfaces. However, even without profuse outgrowth, electrical and chemical synapses develop between neighbouring neurones. The type of synapse depends predictably on the types of neurones within the cell pair. Since the development of a synapse can be followed with time in culture, the sequential events can each be studied separately for this multi-step process. PMID:3323399

  7. Mutations changing tropomodulin affinity for tropomyosin alter neurite formation and extension.

    PubMed

    Moroz, Natalia; Guillaud, Laurent; Desai, Brinda; Kostyukova, Alla S

    2013-01-01

    Assembly of the actin cytoskeleton is an important part of formation of neurites in developing neurons. Tropomodulin, a tropomyosin-dependent capping protein for the pointed end of the actin filament, is one of the key players in this process. Tropomodulin binds tropomyosin in two binding sites. Tmod1 and Tmod2, tropomodulin isoforms found in neurons, were overexpressed in PC12 cells, a model system for neuronal differentiation. Tmod1 did not affect neuronal differentiation; while cells expressing Tmod2 showed a significant reduction in the number and the length of neurites. Both tropomodulins bind short α-, γ- and δ-tropomyosin isoforms. Mutations in one of the tropomyosin-binding sites of Tmod1, which increased its affinity to short γ- and δ-tropomyosin isoforms, caused a decrease in binding short α-tropomyosin isoforms along with a 2-fold decrease in the length of neurites. Our data demonstrate that Tmod1 is involved in neuronal differentiation for proper neurite formation and outgrowth, and that Tmod2 inhibits these processes. The mutations in the tropomyosin-binding site of Tmod1 impair neurite outgrowth, suggesting that the integrity of this binding site is critical for the proper function of Tmod1 during neuronal differentiation. PMID:23638401

  8. Bingham-NODDI: Mapping anisotropic orientation dispersion of neurites using diffusion MRI.

    PubMed

    Tariq, Maira; Schneider, Torben; Alexander, Daniel C; Gandini Wheeler-Kingshott, Claudia A; Zhang, Hui

    2016-06-01

    This paper presents Bingham-NODDI, a clinically-feasible technique for estimating the anisotropic orientation dispersion of neurites. Direct quantification of neurite morphology on clinical scanners was recently realised by a diffusion MRI technique known as neurite orientation dispersion and density imaging (NODDI). However in its current form NODDI cannot estimate anisotropic orientation dispersion, which is widespread in the brain due to common fanning and bending of neurites. This work proposes Bingham-NODDI that extends the NODDI formalism to address this limitation. Bingham-NODDI characterises anisotropic orientation dispersion by utilising the Bingham distribution to model neurite orientation distribution. The new model estimates the extent of dispersion about the dominant orientation, separately along the primary and secondary dispersion orientations. These estimates are subsequently used to estimate the overall dispersion about the dominant orientation and the dispersion anisotropy. We systematically evaluate the ability of the new model to recover these key parameters of anisotropic orientation dispersion with standard NODDI protocol, both in silico and in vivo. The results demonstrate that the parameters of the proposed model can be estimated without additional acquisition requirements over the standard NODDI protocol. Thus anisotropic dispersion can be determined and has the potential to be used as a marker for normal brain development and ageing or in pathology. We additionally find that the original NODDI model is robust to the effects of anisotropic orientation dispersion, when the quantification of anisotropic dispersion is not of interest. PMID:26826512

  9. Tiam1 mediates neurite outgrowth induced by ephrin-B1 and EphA2

    PubMed Central

    Tanaka, Masamitsu; Ohashi, Riuko; Nakamura, Ritsuko; Shinmura, Kazuya; Kamo, Takaharu; Sakai, Ryuichi; Sugimura, Haruhiko

    2004-01-01

    Bidirectional signals mediated by Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, play pivotal roles in the formation of neural networks by induction of both collapse and elongation of neurites. However, the downstream molecular modules to deliver these cues are largely unknown. We report here that the interaction of a Rac1-specific guanine nucleotide-exchanging factor, Tiam1, with ephrin-B1 and EphA2 mediates neurite outgrowth. In cells coexpressing Tiam1 and ephrin-B1, Rac1 is activated by the extracellular stimulation of clustered soluble EphB2 receptors. Similarly, soluble ephrin-A1 activates Rac1 in cells coexpressing Tiam1 and EphA2. Cortical neurons from the E14 mouse embryos and neuroblastoma cells significantly extend neurites when placed on surfaces coated with the extracellular domain of EphB2 or ephrin-A1, which were abolished by the forced expression of the dominant-negative mutant of ephrin-B1 or EphA2. Furthermore, the introduction of a dominant-negative form of Tiam1 also inhibits neurite outgrowth induced by the ephrin-B1 and EphA2 signals. These results indicate that Tiam1 is required for neurite outgrowth induced by both ephrin-B1-mediated reverse signaling and EphA2-mediated forward signaling. PMID:14988728

  10. Two stages in neurite formation distinguished by differences in tubulin metabolism.

    PubMed

    Sekimoto, S; Tashiro, T; Komiya, Y

    1995-01-01

    Changes in tubulin solubility during neurite formation were studied biochemically using rat dorsal root ganglion neurons in culture. When fractionated with Ca(2+)-containing buffer at low temperature, a considerable proportion of total cellular tubulin was recovered in the insoluble fraction. We designated this cold/Ca(2+)-insoluble tubulin (InsT) and distinguished it from cold/Ca(2+)-soluble tubulin (SoIT). From the relative amount of InsT, neurite formation was found to proceed through two distinct stages. The first 6 days after plating (stage 1) in which the proportion of InsT increased dramatically (from 5 to 60%) coincided with neurite outgrowth. In the following period (stage 2), a constant level of InsT was maintained, whereas neurite maturation took place. Pulse-labeling experiments further revealed that the two stages differed significantly in terms of tubulin metabolism. High rates of synthesis as well as conversion from SoIT to InsT were observed in stage 1, whereas stage 2 was characterized by a decrease in both of these rates and an increase in the rate of degradation. The results show for the first time the coordinated changes in tubulin metabolism that underlie the process of neurite formation. PMID:7798932

  11. Lignosus rhinocerus (Cooke) Ryvarden: A Medicinal Mushroom That Stimulates Neurite Outgrowth in PC-12 Cells

    PubMed Central

    Eik, Lee-Fang; Naidu, Murali; David, Pamela; Wong, Kah-Hui; Tan, Yee-Shin; Sabaratnam, Vikineswary

    2012-01-01

    A national treasure mushroom, Lignosus rhinocerus, has been used to treat variety of ailments by local and indigenous communities in Malaysia. The aim of this study was to investigate the potential of the most valuable part of L. rhinocerus, the sclerotium, on neurite outgrowth activity by using PC-12Adh cell line. Differentiated cells with one thin extension at least double the length of the cell diameter were scored positive. Our results showed that aqueous sclerotium L. rhinocerus extract induced neurite outgrowths of 24.4% and 42.1% at 20 μg/mL (w/v) of aqueous extract alone and a combination of 20 μg/mL (w/v) aqueous extract and 30 ng/mL (w/v) of NGF, respectively. Combination of NGF and sclerotium extract had additive effects and enhanced neurite outgrowth. Neuronal differentiation was demonstrated by indirect immunofluorescence of neurofilament protein. Aqueous sclerotium extract contained neuroactive compounds that stimulated neurite outgrowth in vitro. To our knowledge this is the first report on neurite-stimulating activities of L. rhinocerus. PMID:22203867

  12. Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity

    PubMed Central

    Ding, Yuemin; Li, Yuying; Lu, Lingchao; Zhang, Ruyi; Zeng, Linghui; Wang, Linlin; Zhang, Xiong

    2015-01-01

    Nischarin is a cytoplasmic protein expressed in various organs that plays an inhibitory role in cell migration and invasion and the carcinogenesis of breast cancer cells. We previously reported that Nischarin is highly expressed in neuronal cell lines and is differentially expressed in the brain tissue of adult rats. However, the physiological function of Nischarin in neural cells remains unknown. Here, we show that Nischarin is expressed in rat primary cortical neurons but not in astrocytes. Nischarin is localized around the nucleus and dendrites. Using shRNA to knockdown the expression of endogenous Nischarin significantly increases the percentage of neurite-bearing cells, remarkably increases neurite length, and accelerates neurite extension in neuronal cells. Silencing Nischarin expression also promotes dendrite elongation in rat cortical neurons where Nischarin interacts with p21-activated kinase 1/2 (PAK1/2) and negatively regulates phosphorylation of both PAK1 and PAK2. The stimulation of neurite growth observed in cells with decreased levels of Nischarin is partially abolished by IPA3-mediated inhibition of PAK1 activity. Our findings indicate that endogenous Nischarin inhibits neurite outgrowth by blocking PAK1 activation in neurons. PMID:26670864

  13. Essential role of NKCC1 in NGF-induced neurite outgrowth

    SciTech Connect

    Nakajima, Ken-ichi; Miyazaki, Hiroaki; Niisato, Naomi; Marunaka, Yoshinori . E-mail: marunaka@koto.kpu-m.ac.jp

    2007-08-03

    The Na{sup +}/K{sup +}/2Cl{sup -} cotransporter (NKCC) mediates electroneutral transport of 2Cl{sup -} coupled with Na{sup +} and K{sup +} across the plasma membrane, and plays crucial roles in Cl{sup -} uptake into the cells, homeostasis of cellular Cl{sup -}, and cell volume regulation. However, we have very limited information on the roles of ion transporters in neurite outgrowth in neuronal cells. In the present study, we report the role of NKCC1 (an isoform of NKCC) in NGF-induced neurite outgrowth of rat pheochromocytoma PC12D cells. The expression level of NKCC1 protein was increased by NGF treatment. Knock-down of NKCC1 by RNA interference (RNAi) drastically diminished the NGF-induced neurite outgrowth. Transfection of enhanced green fluorescent protein (EGFP)-tagged rat NKCC1 into cells for clarification of intracellular localization of NKCC1 revealed that the EGFP-rNKCC1 was mainly localized in the plasma membrane at growth cone during neurite outgrowth. These observations suggest that NKCC1 plays a fundamental role in NGF-induced neurite outgrowth of PC12D cells.

  14. Enhanced Neurite Growth from Mammalian Neurons in Three-Dimensional Salmon Fibrin Gels

    PubMed Central

    Ju, Yo-El; Janmey, Paul A.; McCormick, Margaret; Sawyer, Evelyn S.; Flanagan, Lisa A.

    2007-01-01

    Three-dimensional fibrin matrices have been used as cellular substrates in vitro and as bridging materials for central nervous system repair. Cells can be embedded within fibrin gels since the polymerization process is non-toxic, making fibrin an attractive scaffold for transplanted cells. Most studies have utilized fibrin prepared from human or bovine blood proteins. However, fish fibrin may be well suited for neuronal growth since fish undergo remarkable central nervous system regeneration and molecules implicated in this process are present in fibrin. We assessed the growth of mammalian central nervous system neurons in bovine, human, and salmon fibrin and found that salmon fibrin gels encouraged the greatest degree of neurite (dendrite and axon) growth and were the most resistant to degradation by cellular proteases. The neurite growth-promoting effect was not due to the thrombin used to polymerize the gels or to any copurifying plasminogen. Co-purified fibronectin partially accounted for the effect on neurites, and blockade of fibrinogen/fibrin-binding integrins markedly decreased neurite growth. Anion exchange chromatography revealed different elution profiles for salmon and mammalian fibrinogens. These data demonstrate that salmon fibrin encourages the growth of neurites from mammalian neurons and suggest that salmon fibrin may be a beneficial scaffold for neuronal regrowth after CNS injury. PMID:17258313

  15. Barchan dunes morphology dynamics under different environmental conditions

    NASA Astrophysics Data System (ADS)

    Dluzewski, M.

    2012-04-01

    The aim of this study was to emphasize significance of diversified dynamics of barchans dune morphology. We analyzed and compared barchans found in two dune fields: Kharga (S Egypt) and Tarfaya-Laâyoune (S-Morocco). These dune fields are characterized by significantly different factors responsible for dunes development e.g. textural and mineralogical composition of dune sand, dune sand moisture, air humidity, inter dune vegetation cover. For each investigated dune filed and study period (2008, 2010, 2012 for Kharga and 2007, 2011, 2012 for Tarfaya-Laâyoune dune fields) detailed shape measurement of 20 simple isolated barchans of different dune sizes was made. The ± 10-2 m horizontal and ± 1,5 10-2m vertical accuracy was obtained (1 measuring point per 1m2 on average).In order to compare barchan dunes morphology and to determine depositional and erosional patterns, the 3D models were created. For better understanding of this processes, sand bulk density of barchan surface was measured (1 measuring point per 2m2 on average). The velocity of dunes in relation to dune shape was also analyzed. The results show that the relationship between typically correlated parameters change during movement of the barchans. Most values change by a few percent per year (slip face height, dune base area and dune volume) or by a dozen or so percent per year (windward side length, horns length and width). We obtain good linear relationship (with 0,05 significant level) between slip face height and the dune base area (0,77 < R2 < 0,83), dune volume (0,66 < R2 < 0,72), windward side length (0,58 < R2 < 0,87), horns length (0,71 < R2 < 0,90) or horns width (0,79 < R2 < 0,93). The linear relationship between displacement rate and the morphological parameters is not strong (0,54< R2 < 0,81) for Kharga dune field and (0,41< R2 < 0,66) for Tarfaya-Laâyoune dune field. We noted also good linear relationship between displacement rate and the angle of span of the horns (R2=0,73 on Tarfaya

  16. Moderately nonlinear diffuse-charge dynamics under an ac voltage

    NASA Astrophysics Data System (ADS)

    Stout, Robert F.; Khair, Aditya S.

    2015-09-01

    The response of a symmetric binary electrolyte between two parallel, blocking electrodes to a moderate amplitude ac voltage is quantified. The diffuse charge dynamics are modeled via the Poisson-Nernst-Planck equations for a dilute solution of point-like ions. The solution to these equations is expressed as a Fourier series with a voltage perturbation expansion for arbitrary Debye layer thickness and ac frequency. Here, the perturbation expansion in voltage proceeds in powers of Vo/(kBT /e ) , where Vo is the amplitude of the driving voltage and kBT /e is the thermal voltage with kB as Boltzmann's constant, T as the temperature, and e as the fundamental charge. We show that the response of the electrolyte remains essentially linear in voltage amplitude at frequencies greater than the RC frequency of Debye layer charging, D /λDL , where D is the ion diffusivity, λD is the Debye layer thickness, and L is half the cell width. In contrast, nonlinear response is predicted at frequencies below the RC frequency. We find that the ion densities exhibit symmetric deviations from the (uniform) equilibrium density at even orders of the voltage amplitude. This leads to the voltage dependence of the current in the external circuit arising from the odd orders of voltage. For instance, the first nonlinear contribution to the current is O (Vo3) which contains the expected third harmonic but also a component oscillating at the applied frequency. We use this to compute a generalized impedance for moderate voltages, the first nonlinear contribution to which is quadratic in Vo. This contribution predicts a decrease in the imaginary part of the impedance at low frequency, which is due to the increase in Debye layer capacitance with increasing Vo. In contrast, the real part of the impedance increases at low frequency, due to adsorption of neutral salt from the bulk to the Debye layer.

  17. Dynamics of Dark-Fly Genome Under Environmental Selections

    PubMed Central

    Izutsu, Minako; Toyoda, Atsushi; Fujiyama, Asao; Agata, Kiyokazu; Fuse, Naoyuki

    2015-01-01

    Environmental adaptation is one of the most fundamental features of organisms. Modern genome science has identified some genes associated with adaptive traits of organisms, and has provided insights into environmental adaptation and evolution. However, how genes contribute to adaptive traits and how traits are selected under an environment in the course of evolution remain mostly unclear. To approach these issues, we utilize “Dark-fly”, a Drosophila melanogaster line maintained in constant dark conditions for more than 60 years. Our previous analysis identified 220,000 single nucleotide polymorphisms (SNPs) in the Dark-fly genome, but did not clarify which SNPs of Dark-fly are truly adaptive for living in the dark. We found here that Dark-fly dominated over the wild-type fly in a mixed population under dark conditions, and based on this domination we designed an experiment for genome reselection to identify adaptive genes of Dark-fly. For this experiment, large mixed populations of Dark-fly and the wild-type fly were maintained in light conditions or in dark conditions, and the frequencies of Dark-fly SNPs were compared between these populations across the whole genome. We thereby detected condition-dependent selections toward approximately 6% of the genome. In addition, we observed the time-course trajectory of SNP frequency in the mixed populations through generations 0, 22, and 49, which resulted in notable categorization of the selected SNPs into three types with different combinations of positive and negative selections. Our data provided a list of about 100 strong candidate genes associated with the adaptive traits of Dark-fly. PMID:26637434

  18. Effects of nerve growth factor and heart cell conditioned medium on neurite regeneration of aged sympathetic neurons in culture.

    PubMed

    Uchida, Y; Tomonaga, M

    1985-11-25

    The effects of nerve growth factor (NGF) and heart-cell-conditioned medium (HCM) on the neurite regeneration of aged sympathetic neurons were investigated in culture. Investigation of HCM was carried out by two different methods: one was the use of whole HCM on collagen substratum, which reflected component(s) effective in solution (HCM-S); the other was the use of polyornithine (PORN)-binding component(s) (P-HCM). Superior cervical ganglion neurons prepared from male mice from 6 to 30 months of age were cultured in MEM-10% FCS on collagen or gelatin-PORN substratum for 3 days. The number of neurons with neurites and the length of neurites were quantified as neurite production and elongation, respectively. Neuronal survival was not affected by addition of NGF, HCM-S or P-HCM. Neurite production of early adult neurons was enhanced by NGF, HCM-S or P-HCM. In contrast, neurite production of aged neurons was enhanced by only HCM-S, but not NGF or P-HCM. HCM-S did not promote neurite elongation in neurons at any age. Neurite elongation of early adult neurons was enhanced by NGF or P-HCM. Neurite elongation of aged neurons was enhanced by P-HCM. However, responsiveness of NGF for neurite elongation varied according to substrata. No age-related difference was found in neurite production and elongation in the absence of NGF, HCM-S or P-HCM. These results indicate that responsiveness of aged sympathetic neurons is various in different growth factors. PMID:3840716

  19. Moderately nonlinear diffuse-charge dynamics under an ac voltage.

    PubMed

    Stout, Robert F; Khair, Aditya S

    2015-09-01

    The response of a symmetric binary electrolyte between two parallel, blocking electrodes to a moderate amplitude ac voltage is quantified. The diffuse charge dynamics are modeled via the Poisson-Nernst-Planck equations for a dilute solution of point-like ions. The solution to these equations is expressed as a Fourier series with a voltage perturbation expansion for arbitrary Debye layer thickness and ac frequency. Here, the perturbation expansion in voltage proceeds in powers of V_{o}/(k_{B}T/e), where V_{o} is the amplitude of the driving voltage and k_{B}T/e is the thermal voltage with k_{B} as Boltzmann's constant, T as the temperature, and e as the fundamental charge. We show that the response of the electrolyte remains essentially linear in voltage amplitude at frequencies greater than the RC frequency of Debye layer charging, D/λ_{D}L, where D is the ion diffusivity, λ_{D} is the Debye layer thickness, and L is half the cell width. In contrast, nonlinear response is predicted at frequencies below the RC frequency. We find that the ion densities exhibit symmetric deviations from the (uniform) equilibrium density at even orders of the voltage amplitude. This leads to the voltage dependence of the current in the external circuit arising from the odd orders of voltage. For instance, the first nonlinear contribution to the current is O(V_{o}^{3}) which contains the expected third harmonic but also a component oscillating at the applied frequency. We use this to compute a generalized impedance for moderate voltages, the first nonlinear contribution to which is quadratic in V_{o}. This contribution predicts a decrease in the imaginary part of the impedance at low frequency, which is due to the increase in Debye layer capacitance with increasing V_{o}. In contrast, the real part of the impedance increases at low frequency, due to adsorption of neutral salt from the bulk to the Debye layer. PMID:26465471

  20. Venom Down Under: Dynamic Evolution of Australian Elapid Snake Toxins

    PubMed Central

    Jackson, Timothy N. W.; Sunagar, Kartik; Undheim, Eivind A. B.; Koludarov, Ivan; Chan, Angelo H. C.; Sanders, Kate; Ali, Syed A.; Hendrikx, Iwan; Dunstan, Nathan; Fry, Bryan G.

    2013-01-01

    Despite the unparalleled diversity of venomous snakes in Australia, research has concentrated on a handful of medically significant species and even of these very few toxins have been fully sequenced. In this study, venom gland transcriptomes were sequenced from eleven species of small Australian elapid snakes, from eleven genera, spanning a broad phylogenetic range. The particularly large number of sequences obtained for three-finger toxin (3FTx) peptides allowed for robust reconstructions of their dynamic molecular evolutionary histories. We demonstrated that each species preferentially favoured different types of α-neurotoxic 3FTx, probably as a result of differing feeding ecologies. The three forms of α-neurotoxin [Type I (also known as (aka): short-chain), Type II (aka: long-chain) and Type III] not only adopted differential rates of evolution, but have also conserved a diversity of residues, presumably to potentiate prey-specific toxicity. Despite these differences, the different α-neurotoxin types were shown to accumulate mutations in similar regions of the protein, largely in the loops and structurally unimportant regions, highlighting the significant role of focal mutagenesis. We theorize that this phenomenon not only affects toxin potency or specificity, but also generates necessary variation for preventing/delaying prey animals from acquiring venom-resistance. This study also recovered the first full-length sequences for multimeric phospholipase A2 (PLA2) ‘taipoxin/paradoxin’ subunits from non-Oxyuranus species, confirming the early recruitment of this extremely potent neurotoxin complex to the venom arsenal of Australian elapid snakes. We also recovered the first natriuretic peptides from an elapid that lack the derived C-terminal tail and resemble the plesiotypic form (ancestral character state) found in viper venoms. This provides supporting evidence for a single early recruitment of natriuretic peptides into snake venoms. Novel forms of kunitz

  1. Interfacial dynamics of two liquids under an oscillating gravitational field

    NASA Technical Reports Server (NTRS)

    Duval, Walter M. B.; Jacqmin, David A.

    1990-01-01

    The evolution of two miscible liquids meeting at an initially sharp interface inside a cavity under microgravity g-jitter conditions is studied numerically. The response of the interface and kinematics of the flowfield to various g-jitter accelerations and aspect ratio variations is shown. The interface region acts like a vortex source sheet, and it can be unstable to Kelvin-Helmholtz and Rayleigh-Taylor instabilities. The vortices produced along the interface can serve as a stirring mechanism to promote local mixing. Below the critical Stokes-Reynolds number, the destabilization of the interface results in deformation into wavy structures. In some parameter regions, these structures oscillate in time; in others, they are quasi-steady. Above the critical Stokes-Reynolds number, 'chaotic' instability results, and the interface breaks into concentration pockets. The morphology of the initial breakup is similar to observed Rayleigh-Taylor instability. Subsequent mixing of the two fluids after the breakup of the interface is then very rapid.

  2. Mechanical Model for Dynamic Behavior of Concrete Under Impact Loading

    NASA Astrophysics Data System (ADS)

    Sun, Yuanxiang

    Concrete is a geo-material which is used substantively in the civil building and military safeguard. One coupled model of damage and plasticity to describe the complex behavior of concrete subjected to impact loading is proposed in this research work. The concrete is assumed as homogeneous continuum with pre-existing micro-cracks and micro-voids. Damage to concrete is caused due to micro-crack nucleation, growth and coalescence, and defined as the probability of fracture at a given crack density. It induces a decrease of strength and stiffness of concrete. Compaction of concrete is physically a collapse of the material voids. It produces the plastic strain in the concrete and, at the same time, an increase of the bulk modulus. In terms of crack growth model, micro-cracks are activated, and begin to propagate gradually. When crack density reaches a critical value, concrete takes place the smashing destroy. The model parameters for mortar are determined using plate impact experiment with uni-axial strain state. Comparison with the test results shows that the proposed model can give consistent prediction of the impact behavior of concrete. The proposed model may be used to design and analysis of concrete structures under impact and shock loading. This work is supported by State Key Laboratory of Explosion science and Technology, Beijing Institute of Technology (YBKT14-02).

  3. Clustering and decoherence of correlated spins under double quantum dynamics

    NASA Astrophysics Data System (ADS)

    Sánchez, Claudia M.; Acosta, Rodolfo H.; Levstein, Patricia R.; Pastawski, Horacio M.; Chattah, Ana K.

    2014-10-01

    We present an improved approach for the study of the evolution of spin correlations and decoherence in multiple quantum nuclear magnetic resonance experiments. The infinite system, constituted by the protons of a polycrystalline adamantane sample, evolves under a double quantum Hamiltonian. The distribution of multiple quantum coherence orders is represented by a contribution of spin clusters with different sizes that exchange spins, increasing their size with the evolution time. A cluster with nearly exponential growth at all times is observed, in agreement with previous models. Remarkably, a small cluster that stabilizes in a size corresponding to 18 correlated spins is revealed. In addition, by performing a renormalization of the obtained data with the experimental Loschmidt echo, the contribution of the different clusters to the observable signal is determined. This procedure accounts for the effect of decoherence on the evolution of the system, and allows setting the range of confidence of the experimental data. Our analysis confirms the natural hint that, correlated states involving higher coherence orders are far more sensitive to the uncontrolled decoherent interactions, than those involving lower orders.

  4. Immunosuppressant FK506 promotes neurite outgrowth in cultures of PC12 cells and sensory ganglia.

    PubMed Central

    Lyons, W E; George, E B; Dawson, T M; Steiner, J P; Snyder, S H

    1994-01-01

    The immunosuppressant drug FK506 acts by binding to receptor proteins, FK506-binding proteins (FKBPs), which in turn can bind to and regulate a Ca(2+)-dependent phosphatase, calcineurin, and a Ca2+ release channel, the ryanodine receptor. Based on our findings in regeneration models that levels of FKBPs during neural regeneration parallel those of growth-associated protein GAP43, a calcineurin substrate that regulates neurite extension, we examined effects of FK506 in PC12 rat pheochromocytoma cells and in rat sensory ganglia. FK506 enhances neurite outgrowth in both systems by increasing sensitivity to nerve growth factor. Blockade of FK506 actions in sensory ganglia by rapamycin, an FK506 antagonist, establishes that these effects involve FKBPs. Rapamycin itself stimulates neurite outgrowth in PC12 cells. These drug effects are detected at subnanomolar concentrations, suggesting therapeutic application in diseases involving neural degeneration. Images PMID:7512727

  5. Bioassay, isolation and studies on the mechanism of action of neurite extension factor

    NASA Technical Reports Server (NTRS)

    Kligman, D.

    1984-01-01

    The identification and purification of molecules active in promoting neurite outgrowth requires a sensitive reproducible bioassay. A quantitative bioassay was utilized to purify a neurite extension factor (NEF) based on counting the number of phase bright neurons with processes at least equal to one cell body diameter after 20 hrs. in culture is defined, serum free medium. Using a combination of heat treatment DEAE cellulose chromatography and gel filtration, an acidic protein of M sub r = 75,000 was highly purified. Upon reduction, it yields subunits of M sub r = 37,000. Purified fractions are active half maximally at 100 ng/ml in inducing neurite outgrowth in this bioassay. Currently, monoclonal antibodies to NEF are being produced. Female Balb C mice were immunized with the antigen and fusions with mouse myeloma cells will be performed to yield hybridoma cells.

  6. Synthesis of functionalized poly(ester carbonate) with laminin-derived peptide for promoting neurite outgrowth of PC12 cells.

    PubMed

    Xing, Dongming; Ma, Lie; Gao, Changyou

    2014-10-01

    Maleimide-functionalized poly(ester carbonate)s are synthesized by ring-opening copolymerization of furan-maleimide functionalized trimethylene carbonate (FMTMC) with L-lactide and a subsequent retro Diels-Alder reaction. The maleimide groups on poly(ester carbonate)s are amenable to Michael addition with thiol-containing molecules such as 3-mercapto-1-propanol, 2-aminoethanethiol hydrochloride, and mercaptoacetic acid under mild conditions, enabling the formation of biodegradable materials with various functional groups (e.g., hydroxyl, amine, and carboxyl). In particular, the maleimide-functionalized poly(ester carbonate) is clicked with a laminin-derived peptide CQAASIKVAV. In vitro culture of PC12 cells shows that the maleimide-functionalized polymers, especially the CQAASIKVAV-grafted one, could support cell proliferation and neurite outgrowth. The maleimide-functionalized poly(ester carbonate)s provide a versatile platform for diverse functionalization and have comprehensive potential in biomedical engineering. PMID:24962245

  7. Neurite outgrowth on electrospun PLLA fibers is enhanced by exogenous electrical stimulation

    NASA Astrophysics Data System (ADS)

    Koppes, A. N.; Zaccor, N. W.; Rivet, C. J.; Williams, L. A.; Piselli, J. M.; Gilbert, R. J.; Thompson, D. M.

    2014-08-01

    Objective. Both electrical stimuli (endogenous and exogenous) and topographical cues are instructive to axonal extension. This report, for the first time, investigated the relative dominance of directional topographical guidance cues and directional electrical cues to enhance and/or direct primary neurite extension. We hypothesized the combination of electrical stimulation with electrospun fiber topography would induce longer neurite extension from dorsal root ganglia neurons than the presence of electrical stimulation or aligned topography alone. Approach. To test the hypothesis, neurite outgrowth was examined on laminin-coated poly-L-lactide films or electrospun fibers (2 µm in diameter) in the presence or absence of electrical stimulation. Immunostained neurons were semi-automatically traced using Neurolucida software and morphology was evaluated. Main Results. Neurite extension increased 74% on the aligned fibers compared to film controls. Stimulation alone increased outgrowth by 32% on films or fibers relative to unstimulated film controls. The co-presentation of topographical (fibers) with biophysical (electrical stimulation) cues resulted in a synergistic 126% increase in outgrowth relative to unstimulated film controls. Field polarity had no influence on the directionality of neurites, indicating topographical cues are responsible for guiding neurite extension. Significance. Both cues (electrical stimulation and fiber geometry) are modular in nature and can be synergistically applied in conjunction with other common methods in regenerative medicine such as controlled release of growth factors to further influence axonal growth in vivo. The combined application of electrical and aligned fiber topographical guidance cues described herein, if translated in vivo, could provide a more supportive environment for directed and robust axonal regeneration following peripheral nerve injury.

  8. Secretory phospholipases A2 induce neurite outgrowth in PC12 cells.

    PubMed Central

    Nakashima, Satoru; Ikeno, Yutaka; Yokoyama, Tatsuya; Kuwana, Masakazu; Bolchi, Angelo; Ottonello, Simone; Kitamoto, Katsuhiko; Arioka, Manabu

    2003-01-01

    sPLA(2)s (secretory phospholipases A(2)) belong to a broad and structurally diverse family of enzymes that hydrolyse the sn -2 ester bond of glycerophospholipids. We previously showed that a secreted fungal 15 kDa protein, named p15, as well as its orthologue from Streptomyces coelicolor (named Scp15) induce neurite outgrowth in PC12 cells at nanomolar concentrations. We report here that both p15 and Scp15 are members of a newly identified group of fungal/bacterial sPLA(2)s. The phospholipid-hydrolysing activity of p15 is absolutely required for neurite outgrowth induction. Mutants with a reduced PLA(2) activity exhibited a comparable reduction in neurite-inducing activity, and the ability to induce neurites closely matched the capacity of various p15 forms to promote fatty acid release from live PC12 cells. A structurally divergent member of the sPLA(2) family, bee venom sPLA(2), also induced neurites in a phospholipase activity-dependent manner, and the same effect was elicited by mouse group V and X sPLA(2)s, but not by group IB and IIA sPLA(2)s. Lysophosphatidylcholine, but not other lysophospholipids, nor arachidonic acid, elicited neurite outgrowth in an L-type Ca(2+) channel activity-dependent manner. In addition, p15-induced neuritogenesis was unaffected by various inhibitors that block arachidonic acid conversion into bioactive eicosanoids. Altogether, these results delineate a novel, Ca(2+)- and lysophosphatidylcholine-dependent neurotrophin-like role of sPLA(2)s in the nervous system. PMID:12967323

  9. Teneurin-4 promotes cellular protrusion formation and neurite outgrowth through focal adhesion kinase signaling

    PubMed Central

    Suzuki, Nobuharu; Numakawa, Tadahiro; Chou, Joshua; de Vega, Susana; Mizuniwa, Chihiro; Sekimoto, Kaori; Adachi, Naoki; Kunugi, Hiroshi; Arikawa-Hirasawa, Eri; Yamada, Yoshihiko; Akazawa, Chihiro

    2014-01-01

    Teneurin-4 (Ten-4), a transmembrane protein, is highly expressed in the central nervous system; however, its cellular and molecular function in neuronal differentiation remains unknown. In this study, we aimed to elucidate the function of Ten-4 in neurite outgrowth. Ten-4 expression was induced during neurite outgrowth of the neuroblastoma cell line Neuro-2a. Ten-4 protein was localized at the neurite growth cones. Knockdown of Ten-4 expression in Neuro-2a cells decreased the formation of the filopodia-like protrusions and the length of individual neurites. Conversely, overexpression of Ten-4 promoted filopodia-like protrusion formation. In addition, knockdown and overexpression of Ten-4 reduced and elevated the activation of focal adhesion kinase (FAK) and Rho-family small GTPases, Cdc42 and Rac1, key molecules for the membranous protrusion formation downstream of FAK, respectively. Inhibition of the activation of FAK and neural Wiskott-Aldrich syndrome protein (N-WASP), which is a downstream regulator of FAK and Cdc42, blocked protrusion formation by Ten-4 overexpression. Further, Ten-4 colocalized with phosphorylated FAK in the filopodia-like protrusion regions. Together, our findings show that Ten-4 is a novel positive regulator of cellular protrusion formation and neurite outgrowth through the FAK signaling pathway.—Suzuki, N., Numakawa, T., Chou, J., de Vega, S., Mizuniwa, C., Sekimoto, K., Adachi, N., Kunugi, H., Arikawa-Hirasawa, E., Yamada, Y., Akazawa, C. Teneurin-4 promotes cellular protrusion formation and neurite outgrowth through focal adhesion kinase signaling. PMID:24344332

  10. ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons

    SciTech Connect

    Han, Jeong-Ho; Yu, Tae-Hoon; Ryu, Hyun-Hee; Jun, Mi-Hee; Ban, Byung-Kwan; Jang, Deok-Jin; Lee, Jin-A

    2013-08-01

    Tar-DNA binding protein of 43 kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons. Highlights: • The function of nuclear TDP-43 in neurite morphology in mature neurons. • Partial mislocalization of TDP-43 missense mutants into cytosol from nucleus. • Abnormal neurite morphology caused by missense mutants of TDP-43. • The effect of cytosolic expression of TDP-43 in neurite morphology and in cell survival.

  11. Neurite Outgrowth On Electrospun PLLA Fibers Is Enhanced By Exogenous Electrical Stimulation

    PubMed Central

    Koppes, A. N.; Zaccor, N. W.; Rivet, C. J.; Williams, L. A.; Piselli, J. M.; Gilbert, R. J.; Thompson, D. M.

    2014-01-01

    Objective Both electrical stimuli (endogenous and exogenous) and topographical cues are instructive to axonal extension. This report, for the first time, investigated the relative dominance of directional topographical guidance cues and directional electrical cues to enhance and/or direct primary neurite extension. We hypothesized the combination of electrical stimulation with electrospun fiber topography would induce longer neurite extension from DRG neurons than the presence of electrical stimulation or aligned topography alone. Approach To test the hypothesis, neurite outgrowth was examined on laminin-coated poly-L-lactide (PLLA) films or electrospun fibers (2 μm in diameter) in the presence or absence of electrical stimulation. Immunostained neurons were semi-automatically traced using Neurolucida software and morphology was evaluated. Results Neurite extension increased 74% on the aligned fibers compared to film controls. Stimulation alone increased outgrowth by 32% on films or fibers relative to unstimulated film controls. The co-presentation of topographical (fibers) with biophysical (electrical stimulation) cues resulted in a synergistic 126% increase in outgrowth relative to unstimulated film controls. Field polarity had no influence on the directionality of neurite, indicating topographical cues are responsible to guide neurite extension. Significance Both cues (electrical stimulation and fiber geometry) are modular in nature and can be synergistically applied in conjunction with other common methods in regenerative medicine such as controlled release of growth factors to further influence axonal growth in vivo. The combined application of electrical and aligned fiber topographical guidance cues described herein, if translated in vivo, could provide a more supportive environment for directed and robust axonal regeneration following peripheral nerve injury. PMID:24891494

  12. Inhibiting geranylgeranylation increases neurite branching and differentially activates cofilin in cell bodies and growth cones.

    PubMed

    Samuel, Filsy; Reddy, Jairus; Kaimal, Radhika; Segovia, Vianey; Mo, Huanbiao; Hynds, DiAnna L

    2014-08-01

    Inhibitors of the mevalonate pathway, including the highly prescribed statins, reduce the production of cholesterol and isoprenoids such as geranylgeranyl pyrophosphates. The Rho family of small guanine triphosphatases (GTPases) requires isoprenylation, specifically geranylgeranylation, for activation. Because Rho GTPases are primary regulators of actin filament rearrangements required for process extension, neurite arborization, and synaptic plasticity, statins may affect cognition or recovery from nervous system injury. Here, we assessed how manipulating geranylgeranylation affects neurite initiation, elongation, and branching in neuroblastoma growth cones. Treatment with the statin, lovastatin (20 μM), decreased measures of neurite initiation by 17.0 to 19.0 % when a source of cholesterol was present and increased neurite branching by 4.03- to 9.54-fold (regardless of exogenous cholesterol). Neurite elongation was increased by treatment with lovastatin only in cholesterol-free culture conditions. Treatment with lovastatin decreased growth cone actin filament content by up to 24.3 %. In all cases, co-treatment with the prenylation precursor, geranylgeraniol (10 μM), reversed the effect of lovastatin. In a prior work, statin effects on outgrowth were linked to modulating the actin depolymerizing factor, cofilin. In our assays, treatment with lovastatin or geranylgeraniol decreased cofilin phosphorylation in whole cell lysates. However, lovastatin increased cofilin phosphorylation in cell bodies and decreased it in growth cones, indicating differential regulation in specific cell regions. Together, we interpret these data to suggest that protein geranylgeranylation likely regulates growth cone actin filament content and subsequent neurite outgrowth through mechanisms that also affect actin nucleation and polymerization. PMID:24515839

  13. “Spatial Mapping of the Neurite and Soma Proteomes Reveals a Functional Cdc42/Rac Regulatory Network”

    SciTech Connect

    Pertz, Olivier C.; Wang, Yingchun; Yang, Feng; Wang, Wei; gay, laurie J.; Gritsenko, Marina A.; Clauss, Therese RW; Anderson, David J.; Liu, Tao; Auberry, Kenneth J.; Camp, David G.; Smith, Richard D.; Klemke, Richard L.

    2008-02-12

    Neurite extension and growth cone navigation are guided by extracellular cues that control cytoskeletal rearrangements. However, understanding the complex signaling mechanisms that mediate neuritogenesis has been limited by the inability to biochemically separate the neurite and soma for spatial proteomic and bioinformatic analyses. Here, we apply global proteome profiling in combination with a novel neurite purification methodology for comparative analysis of the soma and neurite proteomes of neuroblastoma cells. The spatial relationship of 4855 proteins were mapped revealing networks of signaling proteins that control integrins, the actin cytoskeleton, and axonal guidance in the extending neurite. Bioinformatics and functional analyses revealed a spatially compartmentalized Rac/Cdc42 signaling network that operates in conjunction with multiple GEFs and GAPs to control neurite formation. Interestingly, RNA interference experiments revealed that the different GEFs and GAPs regulate specialized functions during neurite formation including neurite growth and retraction kinetics, cytoskeletal organization, and cell polarity. Our findings provide insight into the spatial organization of signaling networks that enable neuritogenesis and provide a comprehensive system-wide profile of proteins that mediate this process including those that control Rac and Cdc42 signaling.

  14. Preparation of Primary Neurons for Visualizing Neurites in a Frozen-hydrated State Using Cryo-Electron Tomography

    PubMed Central

    Shahmoradian, Sarah H.; Galiano, Mauricio R.; Wu, Chengbiao; Chen, Shurui; Rasband, Matthew N.; Mobley, William C.; Chiu, Wah

    2014-01-01

    Neurites, both dendrites and axons, are neuronal cellular processes that enable the conduction of electrical impulses between neurons. Defining the structure of neurites is critical to understanding how these processes move materials and signals that support synaptic communication. Electron microscopy (EM) has been traditionally used to assess the ultrastructural features within neurites; however, the exposure to organic solvent during dehydration and resin embedding can distort structures. An important unmet goal is the formulation of procedures that allow for structural evaluations not impacted by such artifacts. Here, we have established a detailed and reproducible protocol for growing and flash-freezing whole neurites of different primary neurons on electron microscopy grids followed by their examination with cryo-electron tomography (cryo-ET). This technique allows for 3-D visualization of frozen, hydrated neurites at nanometer resolution, facilitating assessment of their morphological differences. Our protocol yields an unprecedented view of dorsal root ganglion (DRG) neurites, and a visualization of hippocampal neurites in their near-native state. As such, these methods create a foundation for future studies on neurites of both normal neurons and those impacted by neurological disorders. PMID:24561719

  15. Dynamic Response Assessment for the MEMS Accelerometer Under Severe Shock Loads

    NASA Technical Reports Server (NTRS)

    Fan, Mark S.; Shaw, Harry C.

    2001-01-01

    NASA Goddard Space Flight Center (GSFC) has evaluated the dynamic response of a commercial-off-the-shelf (COTS) microelectromechanical systems (MEMS) device made by Analog Device, Inc. The device is designated as ADXL250 and is designed mainly for sensing dynamic acceleration. It is also used to measure the tilting angle of any system or component from its original level position. The device has been in commercial use (e.g., in automobile airbag deployment system as a dual-axial accelerometer and in the electronic game play-station as a tilting sensor) with success, but NASA needs an in-depth assessment of its performance under severe dynamic shock environments. It was realized while planning this evaluation task that two assessments would be beneficial to NASA's missions: (1) severe dynamic shock response under nominal thermal environments; and (2) general dynamic performance under cryogenic environments. The first evaluation aims at obtaining a good understanding of its micromachined structure within a framework of brittle fracture dynamics, while the second evaluation focuses on the structure integrity under cryogenic temperature conditions. The information we gathered from the manufacturer indicated that the environmental stresses under NASA's evaluation program have been far beyond what the device has experienced with commercial applications, for which the device was designed. Thus NASA needs the outcome of this evaluation in order to make the selection for possible use for its missions. This paper provides details of the first evaluation the dynamic response under severe multi-axial single-pulse shock load. It was performed using finite element tools with nonlinear dynamics procedures.

  16. Neuritic Plaques and Cerebrovascular Amyloid in Alzheimer Disease are Antigenically Related

    NASA Astrophysics Data System (ADS)

    Wong, Caine W.; Quaranta, Vito; Glenner, George G.

    1985-12-01

    A synthetic peptide (Asp-Ala-Glu-Phe-Arg-His-Asp-Ser-Gly-Tyr), homologous to the amino terminus of a protein purified from cerebrovascular amyloid (β protein), induced antibodies in BALB/c mice that were used immunohistochemically to stain not only amyloid-laden cerebral vessels but neuritic plaques as well. These findings suggest that the amyloid in neuritic plaques shares antigenic determinants with β protein of cerebral vessels. Since the amino acid compositions of plaque amyloid and cerebrovascular amyloid are similar, it is likely that plaque amyloid also consists of β protein. This possibility suggests a model for the pathogenesis of Alzheimer disease involving β protein.

  17. Research on dynamic creep strain and settlement prediction under the subway vibration loading.

    PubMed

    Luo, Junhui; Miao, Linchang

    2016-01-01

    This research aims to explore the dynamic characteristics and settlement prediction of soft soil. Accordingly, the dynamic shear modulus formula considering the vibration frequency was utilized and the dynamic triaxial test conducted to verify the validity of the formula. Subsequently, the formula was applied to the dynamic creep strain function, with the factors influencing the improved dynamic creep strain curve of soft soil being analyzed. Meanwhile, the variation law of dynamic stress with sampling depth was obtained through the finite element simulation of subway foundation. Furthermore, the improved dynamic creep strain curve of soil layer was determined based on the dynamic stress. Thereafter, it could to estimate the long-term settlement under subway vibration loading by norms. The results revealed that the dynamic shear modulus formula is straightforward and practical in terms of its application to the vibration frequency. The values predicted using the improved dynamic creep strain formula closed to the experimental values, whilst the estimating settlement closed to the measured values obtained in the field test. PMID:27536535

  18. Geometric phase of a qubit driven by a phase noise laser under non-Markovian dynamics

    SciTech Connect

    Berrada, K.

    2014-01-15

    Robustness of the geometric phase (GP) with respect to the environmental effects is a basic condition for an effective quantum computation. Here, we study quantitatively the GP of a two-level atom system driven by a phase noise laser under non-Markovian dynamics in terms of different parameters involved in the whole system. We find that with the change of the damping coupling, the GP is very sensitive to its properties exhibiting long collapse and revival phenomena, which play a significant role in enhancing the stabilization and control of the system dynamics. Moreover, we show that the GP can be considered as a tool for testing and characterizing the nature of the qubit–environment coupling. Due to the significance of how a system is quantum correlated with its environment in the construction of a scalable quantum computer, the entanglement dynamics between the qubit with its environment under external classical noise is evaluated and investigated during the time evolution. -- Highlights: •Geometric phase under noise phase laser. •Dynamics of the geometric phase under non-Markovian dynamics in the presence of classical noise. •Solution of master equation of the system in terms atomic inversion. •Nonlocal correlation between the system and its environment under non-Markovianity.

  19. Targeted Learning of the Mean Outcome under an Optimal Dynamic Treatment Rule

    PubMed Central

    van der Laan, Mark J.; Luedtke, Alexander R.

    2015-01-01

    We consider estimation of and inference for the mean outcome under the optimal dynamic two time-point treatment rule defined as the rule that maximizes the mean outcome under the dynamic treatment, where the candidate rules are restricted to depend only on a user-supplied subset of the baseline and intermediate covariates. This estimation problem is addressed in a statistical model for the data distribution that is nonparametric beyond possible knowledge about the treatment and censoring mechanism. This contrasts from the current literature that relies on parametric assumptions. We establish that the mean of the counterfactual outcome under the optimal dynamic treatment is a pathwise differentiable parameter under conditions, and develop a targeted minimum loss-based estimator (TMLE) of this target parameter. We establish asymptotic linearity and statistical inference for this estimator under specified conditions. In a sequentially randomized trial the statistical inference relies upon a second-order difference between the estimator of the optimal dynamic treatment and the optimal dynamic treatment to be asymptotically negligible, which may be a problematic condition when the rule is based on multivariate time-dependent covariates. To avoid this condition, we also develop TMLEs and statistical inference for data adaptive target parameters that are defined in terms of the mean outcome under the estimate of the optimal dynamic treatment. In particular, we develop a novel cross-validated TMLE approach that provides asymptotic inference under minimal conditions, avoiding the need for any empirical process conditions. We offer simulation results to support our theoretical findings. PMID:26236571

  20. Modeling the dynamic stiffness of cracked reinforced concrete beams under low-amplitude vibration loads

    NASA Astrophysics Data System (ADS)

    Xu, Tengfei; Castel, Arnaud

    2016-04-01

    In this paper, a model, initially developed to calculate the stiffness of cracked reinforced concrete beams under static loading, is used to assess the dynamic stiffness. The model allows calculating the average inertia of cracked beams by taking into account the effect of bending cracks (primary cracks) and steel-concrete bond damage (i.e. interfacial microcracks). Free and forced vibration experiments are used to assess the performance of the model. The respective influence of bending cracks and steel-concrete bond damage on both static and dynamic responses is analyzed. The comparison between experimental and simulated deflections confirms that the effects of both bending cracks and steel-concrete bond loss should be taken into account to assess reinforced concrete stiffness under service static loading. On the contrary, comparison of experimental and calculated dynamic responses reveals that localized steel-concrete bond damages do not influence significantly the dynamic stiffness and the fundamental frequency.

  1. Dynamic fluid loss in hydraulic fracturing under realistic shear conditions in high-permeability rocks

    SciTech Connect

    Navarrete, R.C.; Cawiezel, K.E.; Constien, V.G.

    1996-08-01

    A study of the dynamic fluid loss of hydraulic fracturing fluids under realistic shear conditions is presented. During a hydraulic fracturing treatment, a polymeric solution is pumped under pressure down the well to create and propagate a fracture. Part of the fluid leaks into the rock formation, leaving a skin layer of polymer or polymer filter cake, at the rock surface or in the pore space. This study focuses on the effects of shear rate and permeability on dynamic fluid-loss behavior of crosslinked and linear fracturing gels. Previous studies of dynamic fluid loss have mainly been with low-permeability cores and constant shear rates. Here, the effect of shear history and fluid-loss additive on the dynamic leakoff of high-permeability cores is examined.

  2. Bound eigenstate dynamics under a sudden shift of the well's wall

    SciTech Connect

    Granot, Er'el; Marchewka, Avi

    2010-03-15

    We investigate the dynamics of the eigenstate of an infinite well under an abrupt shift of the well's wall. It is shown that when the shift is small compared to the initial well's dimensions, the short-time behavior changes from the well-known t{sup 3/2} behavior to t{sup 1/2}. It is also shown that the complete dynamical picture converges to a universal function, which has fractal structure with dimensionality D=1.25.

  3. Dynamic Crush Behaviors Of Aluminum Honeycomb Specimens Under Compression Dominant Inclined Loads

    SciTech Connect

    Hong, Sung-tae; Pan, Jwo; Tyan, Tau; Prasad, Priya

    2008-01-01

    The quasi-static and dynamic crush behaviors of aluminum 5052-H38 honeycomb specimens under out-of-plane inclined loads are investigated by experiments. Different types of honeycomb specimens were designed for crush tests under pure compressive and inclined loads with respect to the out-of-plane direction. A test fixture was designed for both quasi-static and dynamic crush tests under inclined loads. The results of the quasi-static crush tests indicate that the normal crush and shear strengths under inclined loads are consistent with the corresponding results under combined loads. The results of the dynamic crush tests indicate that as the impact velocity increases, the normal crush strength increases and the shear strength remains nearly the same. The trends of the normalized normal crush strengths under inclined loads for specimens with different in-plane orientation angles as functions of the impact velocity are very similar to each other. Based on the experimental results, a macroscopic yield criterion as a function of the impact velocity is proposed. The experimental results suggest that as the impact velocity increases, the shape of the macroscopic yield surface changes, or more specifically, the curvature of the yield surface increases near the pure compression state. The experimental results also show similar microscopic progressive folding mechanisms in honeycomb specimens under pure compressive and inclined loads. However, honeycomb specimens under inclined loads show inclined stacking patterns of folds due to the asymmetric location of horizontal plastic hinge lines.

  4. Dynamic permeability of electrically conducting fluids under magnetic fields in annular ducts.

    PubMed

    Cuevas, S; del Río, J A

    2001-07-01

    The dynamic response of an electrically conducting fluid (either Newtonian or Maxwellian) flowing between straight concentric circular cylinders under a constant radial magnetic field, is analyzed. The isothermal flow is studied using the time Fourier transform, so that the dynamic generalization of Darcy's law in the frequency domain is obtained and analytical expressions for the dynamic permeability are derived. For the Newtonian case, the range of frequencies where the dynamic permeability approaches the static value is enlarged the smaller the gap between the cylinders and the higher the magnetic-field strength. For the Maxwell fluid, the presence of the inner cylinder shifts the frequencies that lead to the enhancement of the real part of the dynamic permeability to larger values and increases its maximum values relative to the case where the inner cylinder is absent. In addition, the Ohmic dissipation causes the damping of the amplitude of the response. PMID:11461397

  5. Dynamics of the Onset of Damage in Metals under Shock Loading

    NASA Astrophysics Data System (ADS)

    Koskelo, Aaron; Greenfield, Scott; McClellan, Kenneth; Byler, Darrin; Dickerson, Robert; Paisley, Dennis; Luo, Shengnian; Swift, Damian; Tonks, Davis; Peralta, Pedro

    2007-06-01

    We seek to understand the development of damage in polycrystalline materials under shock loading. Our current focus is on the role material microstructure plays in spall formation. Our approach is to use sensitive dynamic interferometry methods (see Greenfield's and Paisley's presentations at this meeting) to probe surface displacement and velocity dynamics of copper during shock loading using laser-launched flyers. Specimens have either columnar grains or have no more than one or two grain-boundaries between the spall layer and the surface that is monitored. In this way, we expect to unravel the complex surface dynamics observed in terms of loci for damage within the material. The dynamic measurements are to be correlated with pre- and post- shot materials characterization and damage assessment. Variables such as triple points, intergranular orientation mismatches, engineered inclusions and voids, and dynamic development of connections between voids are all part of our current work. This presentation will detail the results to date.

  6. Patterned and functionalized nanofiber scaffolds in three-dimensional hydrogel constructs enhance neurite outgrowth and directional control

    NASA Astrophysics Data System (ADS)

    McMurtrey, Richard J.

    2014-12-01

    Objective. Neural tissue engineering holds incredible potential to restore functional capabilities to damaged neural tissue. It was hypothesized that patterned and functionalized nanofiber scaffolds could control neurite direction and enhance neurite outgrowth. Approach. A method of creating aligned electrospun nanofibers was implemented and fiber characteristics were analyzed using environmental scanning electron microscopy. Nanofibers were composed of polycaprolactone (PCL) polymer, PCL mixed with gelatin, or PCL with a laminin coating. Three-dimensional hydrogels were then integrated with embedded aligned nanofibers to support neuronal cell cultures. Microscopic images were captured at high-resolution in single and multi-focal planes with eGFP-expressing neuronal SH-SY5Y cells in a fluorescent channel and nanofiber scaffolding in another channel. Neuronal morphology and neurite tracking of nanofibers were then analyzed in detail. Main results. Aligned nanofibers were shown to enable significant control over the direction of neurite outgrowth in both two-dimensional (2D) and three-dimensional (3D) neuronal cultures. Laminin-functionalized nanofibers in 3D hyaluronic acid (HA) hydrogels enabled significant alignment of neurites with nanofibers, enabled significant neurite tracking of nanofibers, and significantly increased the distance over which neurites could extend. Specifically, the average length of neurites per cell in 3D HA constructs with laminin-functionalized nanofibers increased by 66% compared to the same laminin fibers on 2D laminin surfaces, increased by 59% compared to 2D laminin-coated surface without fibers, and increased by 1052% compared to HA constructs without fibers. Laminin functionalization of fibers also doubled average neurite length over plain PCL fibers in the same 3D HA constructs. In addition, neurites also demonstrated tracking directly along the fibers, with 66% of neurite lengths directly tracking laminin-coated fibers in 3D HA

  7. Solidification and fcc- to metastable hcp- phase transition in krypton under modulating dynamic pressures

    NASA Astrophysics Data System (ADS)

    Chen, Jing-Yin; Yoo, Choong-Shik; Kim, Minseob; Liermann, Hanns-Peter; Cynn, Hyunchae; Jenei, Zsolt; Evans, William

    2014-03-01

    We describe high-pressure kinetic studies of the solidification, melting and fcc-hcp transitions of Krypton under dynamic loading conditions, using a dynamic-diamond anvil cell (d-DAC) coupled with time-resolved x-ray diffraction. The time-resolved diffraction patterns and dynamic pressure responses show compression-rate dependencies associated with both the decay and growth time constants of the liquid-solid and solid-liquid transitions. According to the Avrami equation, both the solidified and melting processes are spontaneous nucleation and a rod-like (1-D) growth. Furthermore, under dynamic loading conditions, Kr-hcp forms from fcc close to the melting line. The nucleation time of fcc and hcp are very fast, with little dependence of compression rates or shorter than the time resolutions. The threshold pressure for the formation of Kr-hcp is ~ 0.8 GPa at the dynamic loadings of 0.004-13 GPa/s. This work was carried out at DESY. This work was performed under the auspices of DOE by LLNL under contracts(W-7405-Eng-48 and DE-AC52-07NA27344) and funded by the LDRD(11-ERD-046). The work at WSU was funded by NSF-DMR(1203834), DTRA(HDTRA1-12-01-0020).

  8. Synthesis of poly(ester-carbonate) with a pendant acetylcholine analog for promoting neurite growth.

    PubMed

    Xing, Dongming; Ma, Lie; Gao, Changyou

    2014-10-01

    The modification of biodegradable polyesters with bioactive molecules has become an important strategy for controlling neuron adhesion and neurite outgrowth in nerve regeneration. In this study we report a biodegradable poly(ester-carbonate) with a pendant acetylcholine analog, which a neurotransmitter for the enhancement of neuron adhesion and outgrowth. The acetylcholine-functionalized poly(ester-carbonate) (Ach-P(LA-ClTMC)) was prepared by copolymerizing l-lactide (LA) and 5-methyl-5-chloroethoxycarbonyl trimethylene carbonate (ClTMC), followed by quaternization with trimethylamine. The acetylcholine analog content could be modulated by changing the molar feeding fraction of ClTMC. The incorporation of the acetylcholine analog improved the hydrophilicity of the films, but the acetylcholine analog content did not significantly influence the surface morphology of the acetylcholine-functionalized films. The results of PC12 cell culture showed that the acetylcholine analog promoted cell viability and neurite outgrowth in a concentration-dependent manner. The longest length of neurite and the percentage of cells bearing neurites were obtained on the Ach-P(LA-ClTMC)-10 film. All the results indicate that the integration of the acetylcholine analog at an appropriate fraction could be an effective strategy for optimizing the existing biodegradable polyesters for nerve regeneration applications. PMID:24998182

  9. Neurite outgrowth resistance to rho kinase inhibitors in PC12 Adh cell.

    PubMed

    Yin, Hua; Hou, Xiaolin; Tao, Tingrui; Lv, Xiaoman; Zhang, Luyong; Duan, Weigang

    2015-05-01

    Rho kinase (ROCK) inhibitor is a promising agent for neural injury disorders, which mechanism is associated with neurite outgrowth. However, neurite outgrowth resistance occurred when PC12 Adh cell was treated with ROCK inhibitors for a longer time. PC12 Adh cells were treated with ROCK inhibitor Y27632 or NGF for different durations. Neurite outgrowth resistance occurred when PC12 Adh cell exposed to Y27632 (33 µM) for 3 or more days, but not happen when exposed to nerve growth factor (NGF, 100 ng/mL). The gene expression in the PC12 Adh cells treated with Y27632 (33 µM) or NGF (100 ng/mL) for 2 or 4 days was assayed by gene microarray, and the reliability of the results were confirmed by real-time RT-PCR. Cluster analysis proved that the gene expression profile of PC12 Adh cell treated with Y27632 for 4 days was different from that treated with Y27632 for 2 days and those treated with NGF for 2 and 4 days, respectively. Pathway analysis hinted that the neurite outgrowth resistance could be associated with up-regulation of inflammatory pathways, especially rno04610 (complement and coagulation cascades), and down-regulation of cell cycle pathways, especially rno04110. PMID:25571866

  10. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    EPA Science Inventory

    There is a need for rapid, efficient and cost effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be...

  11. Cocaine decreases cell survival and inhibits neurite extension of rat locus coeruleus neurons.

    PubMed

    Snow, D M; Smith, J D; Booze, R M; Welch, M A; Mactutus, C F

    2001-01-01

    Cocaine use during pregnancy is affiliated with neurobehavioral abnormalities in offspring that are associated with problems of attention. Given the putative role of the noradrenergic system in attentional processes, impairments in the noradrenergic system may underlie specific attentionally sensitive, neurobehavioral alterations. Recent data using a clinically relevant intravenous (iv) route of administration show that the norepinephrine cell bodies of the locus coeruleus (LC) are a primary target for in utero cocaine exposure. Cell survival and neurite outgrowth of LC neurons were studied using two paradigms: (1) in vitro, using a physiologically relevant concentration of cocaine, and (2) in vivo, using a clinically relevant intravenous rat model. Fetal cocaine exposure significantly decreased neuronal survival (in vitro: P=.0001, n=24; in vivo: P=.0337, n=30), reduced neurite initiation (in vitro: P=.001, n=24; in vivo: P=.0169, n=30), decreased the number of neurites elaborated (in vivo: P=.0031, n=30), and reduced total neurite length (in vivo: P=.0237, n=30). The results of this novel approach toward an understanding of noradrenergic neurons as they respond to cocaine during development suggest that cocaine may affect behavior by negatively regulating neuronal pathfinding and synaptic connectivity. PMID:11418264

  12. Synergic interaction between amyloid precursor protein and neural cell adhesion molecule promotes neurite outgrowth

    PubMed Central

    Chen, Keping; Lu, Huixia; Gao, Tianli; Xue, Xiulei; Wang, Chunling; Miao, Fengqin

    2016-01-01

    Alzheimer's disease (AD) is one of the most common neurodegenerative diseases worldwide. The main features of AD are the pathological changes of density and distribution of intracellular neurofibrillary tangles (NFT) and extracellular amyloid plaques. The processing of amyloid beta precursor protein (APP) to β-amyloid peptide (Aβ) is one of the critical events in the pathogenesis of AD. In this study, we evaluated the role of the interaction of neural cell adhesion molecule (NCAM) and APP in neurite outgrowth using two different experimental systems: PC12E2 cells and hippocampal neurons that were isolated from wild type, APP knock-in and APP knock-out mice. PC12E2 cells or hippocampal neurons were co-cultured with NCAM-negative or NCAM-positive fibroblasts L929 cells. We found that APP promoted neurite outgrowth of PC12E2 cells and hippocampal neurons in either the presence or absence of NCAM. Secreted APP can rescue the neurite outgrowth in hippocampal neurons from APP knock-out mice. The interaction of APP and NCAM had synergic effect in promoting neurite outgrowth in both PC12E2 cells and hippocampal neurons. Our results suggested that the interaction of APP with NCAM played an important role in AD development and therefore could be a potential therapeutic target for AD treatment. PMID:26883101

  13. ACTION OF 50 HZ MAGNETIC FIELDS ON NEURITE OUTGROWTH IN PHEOCHROMOCYTOMA CELLS

    EPA Science Inventory

    This study tests the capacity of 50-Hz magnetic and electric fields to stimulate neurite outgrowth in PC-12D cells, a cell line which originated from a pheochromocytoma in rat adrenal medulla. he cells were plated on collagen-coated plastic petri dishes and exposed to sinusoidal ...

  14. White matter microstructure pathology in classic galactosemia revealed by neurite orientation dispersion and density imaging.

    PubMed

    Timmers, Inge; Zhang, Hui; Bastiani, Matteo; Jansma, Bernadette M; Roebroeck, Alard; Rubio-Gozalbo, M Estela

    2015-03-01

    White matter abnormalities have been observed in patients with classic galactosemia, an inborn error of galactose metabolism. However, magnetic resonance imaging (MRI) data collected in the past were generally qualitative in nature. Our objective was to investigate white matter microstructure pathology and examine correlations with outcome and behaviour in this disease, by using multi-shell diffusion weighted imaging. In addition to standard diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) was used to estimate density and orientation dispersion of neurites in a group of eight patients (aged 16-21 years) and eight healthy controls (aged 15-20 years). Extensive white matter abnormalities were found: neurite density index (NDI) was lower in the patient group in bilateral anterior areas, and orientation dispersion index (ODI) was increased mainly in the left hemisphere. These specific regional profiles are in agreement with the cognitive profile observed in galactosemia, showing higher order cognitive impairments, and language and motor impairments, respectively. Less favourable white matter properties correlated positively with age and age at onset of diet, and negatively with behavioural outcome (e.g. visual working memory). To conclude, this study provides evidence of white matter pathology regarding density and dispersion of neurites in these patients. The results are discussed in light of suggested pathophysiological mechanisms. PMID:25344151

  15. Intracellular Nogo-A facilitates initiation of neurite formation in mouse midbrain neurons in vitro.

    PubMed

    Kurowska, Z; Brundin, P; Schwab, M E; Li, J-Y

    2014-01-01

    Nogo-A is a transmembrane protein originally discovered in myelin, produced by postnatal CNS oligodendrocytes. Nogo-A induces growth cone collapse and inhibition of axonal growth in the injured adult CNS. In the intact CNS, Nogo-A functions as a negative regulator of growth and plasticity. Nogo-A is also expressed by certain neurons. Neuronal Nogo-A depresses long-term potentiation in the hippocampus and modulates neurite adhesion and fasciculation during development in mice. Here we show that Nogo-A is present in neurons derived from human midbrain (Lund human mesencephalic (LUHMES) cell line), as well as in embryonic and postnatal mouse midbrain (dopaminergic) neurons. In LUHMES cells, Nogo-A was upregulated threefold upon differentiation and neurite extension. Nogo-A was localized intracellularly in differentiated LUHMES cells. Cultured midbrain (dopaminergic) neurons from Nogo-A knock-out mice exhibited decreased numbers of neurites and branches when compared with neurons from wild-type (WT) mice. However, this phenotype was not observed when the cultures from WT mice were treated with an antibody neutralizing plasma membrane Nogo-A. In vivo, neither the regeneration of nigrostriatal tyrosine hydroxylase fibers, nor the survival of nigral dopaminergic neurons after partial 6-hydroxydopamine lesions was affected by Nogo-A deletion. These results indicate that during maturation of cultured midbrain (dopaminergic) neurons, intracellular Nogo-A supports neurite growth initiation and branch formation. PMID:24157929

  16. Transient processes under dynamic excitation of a coherent population trapping resonance

    NASA Astrophysics Data System (ADS)

    Khripunov, S. A.; Radnatarov, D. A.; Kobtsev, S. M.; Yudin, V. I.; Taichenachev, A. V.; Basalaev, M. Yu; Balabas, M. V.; Andryushkov, V. A.; Popkov, I. D.

    2016-07-01

    It is shown for the first time that under dynamic excitation of a coherent population trapping resonance in Rb vapours at different bichromatic pump modulation frequencies from a few tens of hertz and higher, the resonance is dramatically deformed as a result of emerging intensity oscillations of radiation transmitted through an Rb vapour cell. A significant change in the shape of the resonance under its dynamic excitation is confirmed experimentally and theoretically. A possible impact of the identified changes in the shape of the coherent population trapping resonance on the stability of an atomic clock is qualitatively discussed.

  17. Waves of actin and microtubule polymerization drive microtubule-based transport and neurite growth before single axon formation

    PubMed Central

    Winans, Amy M; Collins, Sean R; Meyer, Tobias

    2016-01-01

    Many developing neurons transition through a multi-polar state with many competing neurites before assuming a unipolar state with one axon and multiple dendrites. Hallmarks of the multi-polar state are large fluctuations in microtubule-based transport into and outgrowth of different neurites, although what drives these fluctuations remains elusive. We show that actin waves, which stochastically migrate from the cell body towards neurite tips, direct microtubule-based transport during the multi-polar state. Our data argue for a mechanical control system whereby actin waves transiently widen the neurite shaft to allow increased microtubule polymerization to direct Kinesin-based transport and create bursts of neurite extension. Actin waves also require microtubule polymerization, arguing that positive feedback links these two components. We propose that actin waves create large stochastic fluctuations in microtubule-based transport and neurite outgrowth, promoting competition between neurites as they explore the environment until sufficient external cues can direct one to become the axon. DOI: http://dx.doi.org/10.7554/eLife.12387.001 PMID:26836307

  18. Reelin Prevents Apical Neurite Retraction during Terminal Translocation and Dendrite Initiation

    PubMed Central

    O'Dell, Ryan S.; Cameron, David A.; Zipfel, Warren R.

    2015-01-01

    The mechanisms controlling cortical dendrite initiation and targeting are poorly understood. Multiphoton imaging of developing mouse cortex reveals that apical dendrites emerge by direct transformation of the neuron's leading process during the terminal phase of neuronal migration. During this ∼110 min period, the dendritic arbor increases ∼2.5-fold in size and migration arrest occurs below the first stable branch point in the developing arbor. This dendritic outgrowth is triggered at the time of leading process contact with the marginal zone (MZ) and occurs primarily by neurite extension into the extracellular matrix of the MZ. In reeler cortices that lack the secreted glycoprotein Reelin, a subset of neurons completed migration but then retracted and reorganized their arbor in a tangential direction away from the MZ soon after migration arrest. For these reeler neurons, the tangential oriented primary neurites were longer lived than the radially oriented primary neurites, whereas the opposite was true of wild-type (WT) neurons. Application of Reelin protein to reeler cortices destabilized tangential neurites while stabilizing radial neurites and stimulating dendritic growth in the MZ. Therefore, Reelin functions as part of a polarity signaling system that links dendritogenesis in the MZ with cellular positioning and cortical lamination. SIGNIFICANCE STATEMENT Whether the apical dendrite emerges by transformation of the leading process of the migrating neuron or emerges de novo after migration is completed is unclear. Similarly, it is not clear whether the secreted glycoprotein Reelin controls migration and dendritic growth as related or separate processes. Here, multiphoton microscopy reveals the direct transformation of the leading process into the apical dendrite. This transformation is coupled to the successful completion of migration and neuronal soma arrest occurs below the first stable branch point of the nascent dendrite. Deficiency in Reelin causes

  19. Nimodipine enhances neurite outgrowth in dopaminergic brain slice co-cultures.

    PubMed

    Sygnecka, Katja; Heine, Claudia; Scherf, Nico; Fasold, Mario; Binder, Hans; Scheller, Christian; Franke, Heike

    2015-02-01

    Calcium ions (Ca(2+)) play important roles in neuroplasticity and the regeneration of nerves. Intracellular Ca(2+) concentrations are regulated by Ca(2+) channels, among them L-type voltage-gated Ca(2+) channels, which are inhibited by dihydropyridines like nimodipine. The purpose of this study was to investigate the effect of nimodipine on neurite growth during development and regeneration. As an appropriate model to study neurite growth, we chose organotypic brain slice co-cultures of the mesocortical dopaminergic projection system, consisting of the ventral tegmental area/substantia nigra and the prefrontal cortex from neonatal rat brains. Quantification of the density of the newly built neurites in the border region (region between the two cultivated slices) of the co-cultures revealed a growth promoting effect of nimodipine at concentrations of 0.1μM and 1μM that was even more pronounced than the effect of the growth factor NGF. This beneficial effect was absent when 10μM nimodipine were applied. Toxicological tests revealed that the application of nimodipine at this higher concentration slightly induced caspase 3 activation in the cortical part of the co-cultures, but did neither affect the amount of lactate dehydrogenase release or propidium iodide uptake nor the ratio of bax/bcl-2. Furthermore, the expression levels of different genes were quantified after nimodipine treatment. The expression of Ca(2+) binding proteins, immediate early genes, glial fibrillary acidic protein, and myelin components did not change significantly after treatment, indicating that the regulation of their expression is not primarily involved in the observed nimodipine mediated neurite growth. In summary, this study revealed for the first time a neurite growth promoting effect of nimodipine in the mesocortical dopaminergic projection system that is highly dependent on the applied concentrations. PMID:25447789

  20. Evidence for RNA synthesis-dependent and -independent pathways in stimulation of neurite outgrowth by nerve growth factor

    PubMed Central

    Burstein, David E.; Greene, Lloyd A.

    1978-01-01

    Studies on the mechanism of action of nerve growth factor (NGF) were carried out with PC12 rat pheochromocytoma cells. PC12 cells are uniquely useful for such studies because they respond to, but (unlike normal neurons) do not require, NGF and may undergo either generation or regeneration of neurites in response to NGF. Regeneration is defined here as NGF-dependent regrowth of neurites within 24 hr after subculture of NGF-treated PC12 cells. As in cultures of normal NGF-responsive neurons, neurite regeneration by PC12 cells occurs even in the presence of high concentrations of RNA synthesis inhibitors. Generation of neurites is defined as the de novo initiation of outgrowth when PC12 cells are exposed to NGF for the first time. In contrast to regeneration, neurite generation takes place with a lag of at least 24 hr and is blocked by low concentrations of RNA synthesis inhibitors. Such findings suggest that there are both RNA synthesis-dependent and -independent pathways in the mechanism whereby NGF stimulates neurite outgrowth. In addition, NGF-treated PC12 cells undergo a time-dependent loss of the capacity for neurite regeneration after pretreatment with RNA synthesis inhibitors or withdrawal of NGF. Such findings suggest that (i) initiation of neurite outgrowth requires NGF-stimulated, RNA synthesis-dependent accumulation of intracellular material(s), (ii) once such accumulation occurs, RNA synthesis-independent regeneration can occur (but only in the presence of NGF), and (iii) the turnover of such material(s) in the absence of their replacement leads to loss of the capacity for regeneration. A tentative sequence is presented for the events whereby NGF may stimulate neurite outgrowth. PMID:310552

  1. Characterizing chaotic dynamics from simulations of large strain behavior of a granular material under biaxial compression

    NASA Astrophysics Data System (ADS)

    Small, Michael; Walker, David M.; Tordesillas, Antoinette; Tse, Chi K.

    2013-03-01

    For a given observed time series, it is still a rather difficult problem to provide a useful and compelling description of the underlying dynamics. The approach we take here, and the general philosophy adopted elsewhere, is to reconstruct the (assumed) attractor from the observed time series. From this attractor, we then use a black-box modelling algorithm to estimate the underlying evolution operator. We assume that what cannot be modeled by this algorithm is best treated as a combination of dynamic and observational noise. As a final step, we apply an ensemble of techniques to quantify the dynamics described in each model and show that certain types of dynamics provide a better match to the original data. Using this approach, we not only build a model but also verify the performance of that model. The methodology is applied to simulations of a granular assembly under compression. In particular, we choose a single time series recording of bulk measurements of the stress ratio in a biaxial compression test of a densely packed granular assembly—observed during the large strain or so-called critical state regime in the presence of a fully developed shear band. We show that the observed behavior may best be modeled by structures capable of exhibiting (hyper-) chaotic dynamics.

  2. A NASTRAN DMAP alter for linear buckling analysis under dynamic loading

    NASA Technical Reports Server (NTRS)

    Aiello, Robert A.; Grady, Joseph E.

    1989-01-01

    A modification to the NASTRAN solution sequence for transient analysis with direct time integration (COSMIC NASTRAN rigid format 9) was developed and incorporated into a DMAP alter. This DMAP alter calculates the buckling stability of a dynamically loaded structure, and is used to predict the onset of structural buckling under stress-wave loading conditions. The modified solution sequence incorporates the linear buckling analysis capability (rigid format 5) of NASTRAN into the existing Transient solution rigid format in such a way as to provide a time dependent eigensolution which is used to assess the buckling stability of the structure as it responds to the impulsive load. As a demonstration of the validity of this modified solution procedure, the dynamic buckling of a prismatic bar subjected to an impulsive longitudinal compression is analyzed and compared to the known theoretical solution. In addition, a dynamic buckling analysis is performed for the analytically less tractable problem of the localized dynamic buckling of an initially flawed composite laminate under transverse impact loading. The addition of this DMAP alter to the transient solution sequence in NASTRAN facilitates the computational prediction of both the time at which the onset of dynamic buckling occurs in an impulsively loaded structure, and the dynamic buckling mode shapes of that structure.

  3. Searching target sites on DNA by proteins: Role of DNA dynamics under confinement

    PubMed Central

    Mondal, Anupam; Bhattacherjee, Arnab

    2015-01-01

    DNA-binding proteins (DBPs) rapidly search and specifically bind to their target sites on genomic DNA in order to trigger many cellular regulatory processes. It has been suggested that the facilitation of search dynamics is achieved by combining 3D diffusion with one-dimensional sliding and hopping dynamics of interacting proteins. Although, recent studies have advanced the knowledge of molecular determinants that affect one-dimensional search efficiency, the role of DNA molecule is poorly understood. In this study, by using coarse-grained simulations, we propose that dynamics of DNA molecule and its degree of confinement due to cellular crowding concertedly regulate its groove geometry and modulate the inter-communication with DBPs. Under weak confinement, DNA dynamics promotes many short, rotation-decoupled sliding events interspersed by hopping dynamics. While this results in faster 1D diffusion, associated probability of missing targets by jumping over them increases. In contrast, strong confinement favours rotation-coupled sliding to locate targets but lacks structural flexibility to achieve desired specificity. By testing under physiological crowding, our study provides a plausible mechanism on how DNA molecule may help in maintaining an optimal balance between fast hopping and rotation-coupled sliding dynamics, to locate target sites rapidly and form specific complexes precisely. PMID:26400158

  4. Electrical excitability of outgrowing neurites of embryonic neurones in cultures of dissociated neural plate of Xenopus laevis.

    PubMed Central

    Willard, A L

    1980-01-01

    1. I have studied the electrical excitability of outgrowing processes of individual neurones in cultures made from dissociated neural plates of embryos of Xenopus laevis prior to the time of neurite outgrowth in vivo. 2. The electrical excitability of neurites was tested by stimulating them extracellularly and recording responses with an intracellular electrode in their cell bodies; neurites were excitable at all times examined. 3. The ionic basis of the excitability of neurites was tested by recording from cells while changing the composition of the salines perfusing the cultures. 4. In cultures less than 10 hr old, all neurites tested made responses which depended on Ca2+. The action potentials of the cell bodies were also Ca2+-dependent at these times. 5. Between 10 and 12 hr in culture, a time at which the cell bodies still made Ca2+-dependent action potentials, neurites acquired the ability to make Na+-dependent responses. At these times, two-thirds of neurites tested retained the ability to produce divalent cation-dependent action potentials when perfused with solutions of isotonic Ba2+. 6. After 12 hr in culture, no neurites were observed to make Ca2+-or Ba2+-dependent responses; only Na+-dependent responses were observed. Cells continued to initiate and elongate new neurites until about 24 hr in culture. Thus neurites sent out at different times in culture differed in their development of excitability. 7. Cell bodies making exclusively Ca2+-dependent action potentials could be found until about 15 hr in culture, after which time a Na+-dependent component appeared. Cell bodies could then be observed to make action potentials which depended on both Ca2+ and Na+ until about 3 days in culture. After 3 days, most cell bodies made predominately Na+-dependent action potentials. Unlike the neurites, cell bodies retained the ability to make action potentials in isotonic Ba2+ for as long as the cultures were maintained (up to 5 days). 8. The possibility that changes

  5. Dynamic response of CFRP plates under the action of random acoustic loading

    NASA Astrophysics Data System (ADS)

    White, R. G.; Mousley, R. F.

    Acoustic fatigue design procedures for metallic, stiffened skin, and plate-type structures have been well established and validated in the past for aircraft structures. The advent of CFRP and its use in aircraft has necessitated reappraisal of dynamic design techniques. Experimental and theoretical studies of CFRP plates under the action of random acoustic loading are discussed. Attention is given to the nature and levels of the dynamic strains induced in terms of statistical properties and relative modal contributions, the latter being important in consideration of using simple single mode formulas for dynamic response prediction. The effects of high levels of excitation, up to 160 dB, which can produce nonlinear responses are discussed. The case of forced response of plates under the action of combined static in-plane compressive loading and acoustic excitation is also considered.

  6. Size and Geometry Effects on the Mechanical Properties of Carrara Marble Under Dynamic Loadings

    NASA Astrophysics Data System (ADS)

    Zou, Chunjiang; Wong, Louis Ngai Yuen

    2016-05-01

    The effects of specimen size and geometry on the dynamic mechanical properties of Carrara marble including compressive strength, failure strain and elastic modulus are investigated in this research. Four different groups of specimens of different sizes and cross-sectional geometries are loaded under a wide range of strain rates by the split Hopkinson pressure bar setup. The experimental results indicate that all these mechanical properties are significantly influenced by the specimen size and geometry to different extent, hence highlighting the importance of taking into account of the specimen size and geometry in dynamic tests on rock materials. In addition, the transmission coefficient and the determination of strain rate under dynamic tests are discussed in detail.

  7. A DYNAMIC NONLINEAR MODEL OF OZONE-INDUCED FEV1 RESPONSE UNDER CHANGING EXPOSURE CONDITIONS

    EPA Science Inventory

    A Dynamic Nonlinear Model of Ozone-induced FEV1 Response under Changing Exposure Conditions. 1WF McDonnell, 2PW Stewart, 3MV Smith. 1Human Studies Division, NHEERL, U.S. EPA, RTP, NC. 2University of North Carolina, Chapel Hill, NC. 3ASI, Durham, NC.

    Ozone exposure result...

  8. Nonstationary desertification dynamics of desert oasis under climate change and human interference

    NASA Astrophysics Data System (ADS)

    Huang, Guohe; Qin, Xiaosheng; He, Li; Zhang, Hua; Li, Yongping; Li, Zhong

    2015-12-01

    Desertification is becoming a major ecological concern in arid and semiarid regions, especially under climate change. Globally, it is burning up lands for human habitats with a rapidly spreading tendency. Many scientists have been struggling to explore the related mechanisms. Challenges remain in revealing the fundamental principle in terms of desert-oasis interactions that are associated with nonstationary variations. Here we present a theory of desertification dynamics through examining nonstationary effects of climate change and human interference. We hypothesize that such dynamics can be described as the fate and transport of dry air mass continuously generated from desert. We simulate a region in northwestern China and reveal that dynamics of the nonstationary desertification process is subject to interactive impacts from a variety of factors. Our study moves forward the field of desertification studies through initiation of the dynamics and nonstationarity concepts which allow the fundamental mechanism to be disclosed.

  9. The amyloid precursor protein (APP) triplicated gene impairs neuronal precursor differentiation and neurite development through two different domains in the Ts65Dn mouse model for Down syndrome.

    PubMed

    Trazzi, Stefania; Fuchs, Claudia; Valli, Emanuele; Perini, Giovanni; Bartesaghi, Renata; Ciani, Elisabetta

    2013-07-19

    Intellectual disability in Down syndrome (DS) appears to be related to severe proliferation impairment during brain development. Recent evidence shows that it is not only cellular proliferation that is heavily compromised in DS, but also cell fate specification and dendritic maturation. The amyloid precursor protein (APP), a gene that is triplicated in DS, plays a key role in normal brain development by influencing neural precursor cell proliferation, cell fate specification, and neuronal maturation. APP influences these processes via two separate domains, the APP intracellular domain (AICD) and the soluble secreted APP. We recently found that the proliferation impairment of neuronal precursors (NPCs) from the Ts65Dn mouse model for DS was caused by derangement of the Shh pathway due to overexpression of patched1(Ptch1), its inhibitory regulator. Ptch1 overexpression was related to increased levels within the APP/AICD system. The overall goal of this study was to determine whether APP contributes to neurogenesis impairment in DS by influencing in addition to proliferation, cell fate specification, and neurite development. We found that normalization of APP expression restored the reduced neuronogenesis, the increased astrogliogenesis, and the reduced neurite length of trisomic NPCs, indicating that APP overexpression underpins all aspects of neurogenesis impairment. Moreover, we found that two different domains of APP impair neuronal differentiation and maturation in trisomic NPCs. The APP/AICD system regulates neuronogenesis and neurite length through the Shh pathway, whereas the APP/secreted AP system promotes astrogliogenesis through an IL-6-associated signaling cascade. These results provide novel insight into the mechanisms underlying brain development alterations in DS. PMID:23740250

  10. Impact of under-excitation limit control on power system dynamic performance

    SciTech Connect

    Oliveira, S.E.M. de; Santos, M.G. dos

    1995-11-01

    Several control functions, in addition to terminal voltage control, are performed by the excitation systems of the synchronous machines in a power plant. The under-excitation limit (UEL) is one of these. In this paper the authors deal with the effect of such control on the dynamic performance of power systems. Certain simulation results properly characterize UEL action which, depending on the nature and severity of the contingency, can be relatively fast. The objective is to encourage representation of the under-excitation limit control function in synchronous generator AVR modeling for power system dynamic studies. Essentially, the control acts by precluding excessively under-excited conditions. In practice, it is applied to prevent both operation beyond the steady-state stability limit and the large magnetic losses produced by leakage fluxes in stator winding end-of-turns during machine operation with very small field circuit excitation.

  11. Summary of work completed under the Environmental and Dynamic Equipment Qualification research program (EDQP)

    SciTech Connect

    Steele, R. Jr.; Bramwell, D.L.; Watkins, J.C.; DeWall, K.G.

    1994-02-01

    This report documents the results of the main projects undertaken under the Environmental and Dynamic Equipment Qualification Research Program (EDQP) sponsored by the U.S. Nuclear Regulatory Commission (NRC) under FIN A6322. Lasting from fiscal year 1983 to 1987, the program dealt with environmental and dynamic (including seismic) equipment qualification issues for mechanical and electromechanical components and systems used in nuclear power plants. The research results have since been used by both the NRC and industry. The program included seven major research projects that addressed the following issues: (a) containment purge and vent valves performing under design basis loss of coolant accident loads, (b) containment piping penetrations and isolation valves performing under seismic loadings and design basis and severe accident containment wall displacements, (c) shaft seals for primary coolant pumps performing under station blackout conditions, (d) electrical cabinet internals responding to in-structure generated motion (rattling), and (e) in situ piping and valves responding to seismic loadings. Another project investigating whether certain containment isolation valves will close under design basis conditions was also started under this program. This report includes eight main section, each of which provides a brief description of one of the projects, a summary of the findings, and an overview of the application of the results. A bibliography lists the journal articles, papers, and reports that document the research.

  12. Protein dynamics and motions in relation to their functions: several case studies and the underlying mechanisms

    PubMed Central

    Yang, Li-Quan; Sang, Peng; Tao, Yan; Fu, Yun-Xin; Zhang, Ke-Qin; Xie, Yue-Hui; Liu, Shu-Qun

    2013-01-01

    Proteins are dynamic entities in cellular solution with functions governed essentially by their dynamic personalities. We review several dynamics studies on serine protease proteinase K and HIV-1 gp120 envelope glycoprotein to demonstrate the importance of investigating the dynamic behaviors and molecular motions for a complete understanding of their structure–function relationships. Using computer simulations and essential dynamic (ED) analysis approaches, the dynamics data obtained revealed that: (i) proteinase K has highly flexible substrate-binding site, thus supporting the induced-fit or conformational selection mechanism of substrate binding; (ii) Ca2+ removal from proteinase K increases the global conformational flexibility, decreases the local flexibility of substrate-binding region, and does not influence the thermal motion of catalytic triad, thus explaining the experimentally determined decreased thermal stability, reduced substrate affinity, and almost unchanged catalytic activity upon Ca2+ removal; (iii) substrate binding affects the large concerted motions of proteinase K, and the resulting dynamic pocket can be connected to substrate binding, orientation, and product release; (iv) amino acid mutations 375 S/W and 423 I/P of HIV-1 gp120 have distinct effects on molecular motions of gp120, facilitating 375 S/W mutant to assume the CD4-bound conformation, while 423 I/P mutant to prefer for CD4-unliganded state. The mechanisms underlying protein dynamics and protein–ligand binding, including the concept of the free energy landscape (FEL) of the protein–solvent system, how the ruggedness and variability of FEL determine protein's dynamics, and how the three ligand-binding models, the lock-and-key, induced-fit, and conformational selection are rationalized based on the FEL theory are discussed in depth. PMID:23527883

  13. Dynamic proteome analysis of Cyanothece sp. ATCC 51142 under constant light

    SciTech Connect

    Aryal, Uma K.; Stockel, Jana; Welsh, Eric A.; Gritsenko, Marina A.; Nicora, Carrie D.; Koppenaal, David W.; Smith, Richard D.; Pakrasi, Himadri B.; Jacobs, Jon M.

    2012-02-03

    Understanding the dynamic nature of protein abundances provides insights into protein turnover not readily apparent from conventional, static mass spectrometry measurements. This level of data is particularly informative when surveying protein abundances in biological systems subjected to large perturbations or alterations in environment such as cyanobacteria. Our current analysis expands upon conventional proteomic approaches in cyanobacteria by measuring dynamic changes of the proteome using a 13C15N-L-leucine metabolic labeling in Cyanothece ATCC51142. Metabolically labeled Cyanothece ATCC51142 cells grown under nitrogen sufficient conditions in continuous light were monitored longitudinally for isotope incorporation over a 48 h period, revealing 422 proteins with dynamic changes in abundances. In particular, proteins involved in carbon fixation, pentose phosphate pathway, cellular protection, redox regulation, protein folding, assembly and degradation showed higher levels of isotope incorporation suggesting that these biochemical pathways are important for growth under non-diazotrophic conditions. Calculation of relative isotope abundances (RIA) values allowed to measure actual active protein synthesis over time for different biochemical pathways under non-diazotrophic conditions. Overall results demonstrated the utility of 'non-steady state' pulsed metabolic labeling for systems-wide dynamic quantification of the proteome in Cyanothece ATCC51142 that can also be applied to other cyanobacteria.

  14. Coevolutionary dynamics of networks and games under birth-death and birth mechanisms

    NASA Astrophysics Data System (ADS)

    Huang, Z.-G.; Wu, Z.-X.; Xu, X.-J.; Guan, J.-Y.; Wang, Y.-H.

    2007-08-01

    There is much interest in studying evolutionary games in structured populations, in order to understand how cooperation emerges in communities of egoistic agents. In this paper, we consider a new mechanism for cooperation to survive on networks. Agents are designed to reproduce offspring in proportion to their fitness, i.e., the aggregate payoffs they collected in the previous Prisoner's Dilemma game with neighbours. The population then evolves either by an individual giving birth to an offspring that takes over a random neighbour (birth-death process dynamics as the competition for resources already occupied by others) or by an individual constructing one new site from unexploited resources for its offspring (birth process dynamics as the competition for the unexploited resources which induces the extension of system). The underlying interaction network thus evolves and expands simultaneously with the population dynamics. The birth process dynamics is proved to be one new route that favours cooperators, under which cooperators can successfully resist the invasion of defectors in spite of large cost. Furthermore, under this “birth-death & birth” mechanism, the resulting network has a scale-free degree distribution, a small-world property, and hierarchical topology.

  15. Dynamics of the cell-cycle network under genome-rewiring perturbations

    NASA Astrophysics Data System (ADS)

    Katzir, Yair; Elhanati, Yuval; Averbukh, Inna; Braun, Erez

    2013-12-01

    The cell-cycle progression is regulated by a specific network enabling its ordered dynamics. Recent experiments supported by computational models have shown that a core of genes ensures this robust cycle dynamics. However, much less is known about the direct interaction of the cell-cycle regulators with genes outside of the cell-cycle network, in particular those of the metabolic system. Following our recent experimental work, we present here a model focusing on the dynamics of the cell-cycle core network under rewiring perturbations. Rewiring is achieved by placing an essential metabolic gene exclusively under the regulation of a cell-cycle's promoter, forcing the cell-cycle network to function under a multitasking challenging condition; operating in parallel the cell-cycle progression and a metabolic essential gene. Our model relies on simple rate equations that capture the dynamics of the relevant protein-DNA and protein-protein interactions, while making a clear distinction between these two different types of processes. In particular, we treat the cell-cycle transcription factors as limited ‘resources’ and focus on the redistribution of resources in the network during its dynamics. This elucidates the sensitivity of its various nodes to rewiring interactions. The basic model produces the correct cycle dynamics for a wide range of parameters. The simplicity of the model enables us to study the interface between the cell-cycle regulation and other cellular processes. Rewiring a promoter of the network to regulate a foreign gene, forces a multitasking regulatory load. The higher the load on the promoter, the longer is the cell-cycle period. Moreover, in agreement with our experimental results, the model shows that different nodes of the network exhibit variable susceptibilities to the rewiring perturbations. Our model suggests that the topology of the cell-cycle core network ensures its plasticity and flexible interface with other cellular processes, without

  16. Plant-soil interactions and soil carbon dynamics under climate extremes

    NASA Astrophysics Data System (ADS)

    Bahn, Michael

    2016-04-01

    Climate extremes have been suggested to increase significantly in intensity and frequency in the coming decades, and may influence ecosystem processes and the carbon cycle more profoundly than gradual climate warming. While there is a growing understanding of plant-soil interactions in extreme environments and from lab experiments, we still know very little about how such interactions affect soil carbon dynamics in real-world ecosystems exposed to climate extremes. In this talk I will give a brief overview of the topic and will present evidence from in-situ experiments on plant-soil interactions and their consequences for soil carbon dynamics under severe drought.

  17. A dynamic model for the p53 stress response networks under ion radiation.

    PubMed

    Qi, J-P; Shao, S-H; Li, D-D; Zhou, G-P

    2007-07-01

    P53 controls the cell cycle arrest and cell apoptosis through interaction with the downstream genes and their signal pathways. To stimulate the investigation into the complicated responses of p53 under the circumstance of ion radiation (IR) in the cellular level, a dynamic model for the p53 stress response networks is proposed. The model can be successfully used to simulate the dynamic processes of generating the double-strand breaks (DSBs) and their repairing, ataxia telangiectasia mutated (ATM) activation, as well as the oscillations occurring in the p53-MDM2 feedback loop. PMID:17072789

  18. Lattice dynamics and electronic structure of mixed halofluoride scintillators under high pressure

    SciTech Connect

    Kanchana, V.; Yedukondalu, N.; Vaitheeswaran, G.

    2015-06-24

    We report the structural, lattice dynamics and electronic structure of mixed halo-fluoride scintillators MClF (M = Ca, Sr) based on density functional theory within generalized gradient approximation. The pressure dependent structural parameters and zone centered phonon frequencies are in reasonable agreement with the available experimental data. Both the structures are dynamically stable up to 50 GPa. MClF compounds are found to have a direct band gap along Γ−Γ direction at ambient as well as under pressure. It is found that these materials can serve as good storage phosphors in the low pressure region from the calculated electronic structure and optical spectra.

  19. Analysis of nonlinear dynamic response for delaminated fiber-metal laminated beam under unsteady temperature field

    NASA Astrophysics Data System (ADS)

    Fu, Yiming; Chen, Yang; Zhong, Jun

    2014-10-01

    The nonlinear dynamic response problems of fiber-metal laminated beams with delamination are studied in this paper. Basing on the Timoshenko beam theory, and considering geometric nonlinearity, transverse shear deformation, temperature effect and contact effect, the nonlinear governing equations of motion for fiber-metal laminated beams under unsteady temperature field are established, which are solved by the differential quadrature method, Nermark-β method and iterative method. In numerical examples, the effects of delamination length, delamination depth, temperature field, geometric nonlinearity and transverse shear deformation on the nonlinear dynamic response of the glass reinforced aluminum laminated beam with delamination are discussed in details.

  20. Entanglement and quantum discord dynamics of two atoms under practical feedback control

    SciTech Connect

    Li Yang; Luo Bin; Guo Hong

    2011-07-15

    We study the dynamics of two identical atoms resonantly coupled to a single-mode cavity under practical feedback control, and focus on the detection inefficiency. The entanglement is induced to vanish in finite time by the inefficiency of detection. Counterintuitively, the asymptotic entanglement and quantum discord can be increased by the inefficiency of detection. The noise of detection triggers the control field to create entanglement and discord when no photons are emitted from the atoms. Furthermore, sudden change happens to the dynamics of entanglement.

  1. Quantitative assessment of neurite outgrowth in human embryonic stem-cell derived neurons using automated high-content image analysis

    EPA Science Inventory

    During development neurons undergo a number of morphological changes including neurite outgrowth from the cell body. Exposure to neurotoxicants that interfere with this process may cause in permanent deficits in nervous system function. While many studies have used rodent primary...

  2. Dynamic stability of simply supported composite cylindrical shells under partial axial loading

    NASA Astrophysics Data System (ADS)

    Dey, Tanish; Ramachandra, L. S.

    2015-09-01

    The parametric vibration of a simply supported composite circular cylindrical shell under periodic partial edge loadings is discussed in this article. Donnell's nonlinear shallow shell theory considering first order shear deformation theory is used to model the shell. The applied partial edge loading is represented in terms of a Fourier series and stress distributions within the cylindrical shell are determined by prebuckling analysis. The governing equations of the dynamic instability of shells are derived in terms of displacements (u-v-w) and rotations (φx, φθ). Employing the Galerkin and Bolotin methods the dynamic instability regions are computed. Using the expression for the stress function derived in this paper, the pre-buckling stresses in the cylindrical shell due to partial loading can be calculated explicitly. Numerical results are presented to show the influence of radius-to-thickness ratio, different partial edge loading distributions and shear deformation on the dynamic instability regions. The linear and nonlinear responses in the stable and unstable regions are presented to bring out the characteristic features of the dynamic instability regions, such as the existence of beats, its dependence on forcing frequency and effect of nonlinearity on the response. The effect of dynamic load amplitude on the nonlinear response is also studied. It is found that for higher values of dynamic loading, the shell exhibits chaotic behavior.

  3. Guaifenesin derivatives promote neurite outgrowth and protect diabetic mice from neuropathy.

    PubMed

    Hadimani, Mallinath B; Purohit, Meena K; Vanampally, Chandrashaker; Van der Ploeg, Randy; Arballo, Victor; Morrow, Dwane; Frizzi, Katie E; Calcutt, Nigel A; Fernyhough, Paul; Kotra, Lakshmi P

    2013-06-27

    In diabetic patients, an early index of peripheral neuropathy is the slowing of conduction velocity in large myelinated neurons and a lack of understanding of the basic pathogenic mechanisms hindered therapeutics development. Racemic (R/S)-guaifenesin (1) was identified as a potent enhancer of neurite outgrowth using an in vitro screen. Its R-enantiomer (R)-1 carried the most biological activity, whereas the S-enantiomer (S)-1 was inactive. Focused structural variations to (R/S)-1 was conducted to identify potentially essential groups for the neurite outgrowth activity. In vivo therapeutic studies indicated that both (R/S)-1 and (R)-1 partially prevented motor nerve conduction velocity slowing in a mouse model of type 1 diabetes. In vitro microsomal assays suggested that compounds (R)-1 and (S)-1 are not metabolized rapidly, and PAMPA assay indicated moderate permeability through the membrane. Findings revealed here could lead to the development of novel drugs for diabetic neuropathy. PMID:23758573

  4. Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration☆

    PubMed Central

    Jielile, Jiasharete; Aibai, Minawa; Sabirhazi, Gulnur; Shawutali, Nuerai; Tangkejie, Wulanbai; Badelhan, Aynaz; Nuerduola, Yeermike; Satewalede, Turde; Buranbai, Darehan; Hunapia, Beicen; Jialihasi, Ayidaer; Bai, Jingping; Kizaibek, Murat

    2012-01-01

    Active Achilles tendon kinesitherapy facilitates the functional recovery of a ruptured Achilles tendon. However, protein expression during the healing process remains a controversial issue. New Zealand rabbits, aged 14 weeks, underwent tenotomy followed immediately by Achilles tendon microsurgery to repair the Achilles tendon rupture. The tendon was then immobilized or subjected to postoperative early motion treatment (kinesitherapy). Mass spectrography results showed that after 14 days of motion treatment, 18 protein spots were differentially expressed, among which, 12 were up-regulated, consisting of gelsolin isoform b and neurite growth-related protein collapsing response mediator protein 2. Western blot analysis showed that gelsolin isoform b was up-regulated at days 7–21 of motion treatment. These findings suggest that active Achilles tendon kinesitherapy promotes the neurite regeneration of a ruptured Achilles tendon and gelsolin isoform b can be used as a biomarker for Achilles tendon healing after kinesitherapy. PMID:25317130

  5. Large enhancement in neurite outgrowth on a cell membrane-mimicking conducting polymer.

    PubMed

    Zhu, Bo; Luo, Shyh-Chyang; Zhao, Haichao; Lin, Hsing-An; Sekine, Jun; Nakao, Aiko; Chen, Chi; Yamashita, Yoshiro; Yu, Hsiao-Hua

    2014-01-01

    Although electrically stimulated neurite outgrowth on bioelectronic devices is a promising means of nerve regeneration, immunogenic scar formation can insulate electrodes from targeted cells and tissues, thereby reducing the lifetime of the device. Ideally, an electrode material capable of electrically interfacing with neurons selectively and efficiently would be integrated without being recognized by the immune system and minimize its response. Here we develop a cell membrane-mimicking conducting polymer possessing several attractive features. This polymer displays high resistance towards nonspecific enzyme/cell binding and recognizes targeted cells specifically to allow intimate electrical communication over long periods of time. Its low electrical impedance relays electrical signals efficiently. This material is capable to integrate biochemical and electrical stimulation to promote neural cellular behaviour. Neurite outgrowth is enhanced greatly on this new conducting polymer; in addition, electrically stimulated secretion of proteins from primary Schwann cells can also occur on it. PMID:25060339

  6. Large enhancement in neurite outgrowth on a cell membrane-mimicking conducting polymer

    NASA Astrophysics Data System (ADS)

    Zhu, Bo; Luo, Shyh-Chyang; Zhao, Haichao; Lin, Hsing-An; Sekine, Jun; Nakao, Aiko; Chen, Chi; Yamashita, Yoshiro; Yu, Hsiao-Hua

    2014-07-01

    Although electrically stimulated neurite outgrowth on bioelectronic devices is a promising means of nerve regeneration, immunogenic scar formation can insulate electrodes from targeted cells and tissues, thereby reducing the lifetime of the device. Ideally, an electrode material capable of electrically interfacing with neurons selectively and efficiently would be integrated without being recognized by the immune system and minimize its response. Here we develop a cell membrane-mimicking conducting polymer possessing several attractive features. This polymer displays high resistance towards nonspecific enzyme/cell binding and recognizes targeted cells specifically to allow intimate electrical communication over long periods of time. Its low electrical impedance relays electrical signals efficiently. This material is capable to integrate biochemical and electrical stimulation to promote neural cellular behaviour. Neurite outgrowth is enhanced greatly on this new conducting polymer; in addition, electrically stimulated secretion of proteins from primary Schwann cells can also occur on it.

  7. Anisotropic three-dimensional peptide channels guide neurite outgrowth within a biodegradable hydrogel matrix.

    PubMed

    Musoke-Zawedde, Patricia; Shoichet, Molly S

    2006-09-01

    The objective of this study was to investigate the neurite guidance potential of concentration gradients of glycine-arginine-glycine-aspartic acid-serine (GRGDS) oligopeptides immobilized within three-dimensional patterned cylindrical volumes created in a biodegradable nerve guidance matrix. This was achieved using ultraviolet (UV) laser micropatterning of a hyaluronan (HA) hydrogel matrix modified with S-2-nitrobenzyl cysteine. Upon exposure to focused laser light, the 2-nitrobenzyl group was cleaved, exposing thiol groups which reacted with maleimide-terminated GRGDS exclusively within these laser-defined volumes. We show that the UV laser micropatterning technique can be used to create GRGDS peptide concentration gradients within the oligopeptide channels and that these channels guide neurite outgrowth from primary neural cells. PMID:18458398

  8. Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration.

    PubMed

    Jielile, Jiasharete; Aibai, Minawa; Sabirhazi, Gulnur; Shawutali, Nuerai; Tangkejie, Wulanbai; Badelhan, Aynaz; Nuerduola, Yeermike; Satewalede, Turde; Buranbai, Darehan; Hunapia, Beicen; Jialihasi, Ayidaer; Bai, Jingping; Kizaibek, Murat

    2012-12-15

    Active Achilles tendon kinesitherapy facilitates the functional recovery of a ruptured Achilles tendon. However, protein expression during the healing process remains a controversial issue. New Zealand rabbits, aged 14 weeks, underwent tenotomy followed immediately by Achilles tendon microsurgery to repair the Achilles tendon rupture. The tendon was then immobilized or subjected to postoperative early motion treatment (kinesitherapy). Mass spectrography results showed that after 14 days of motion treatment, 18 protein spots were differentially expressed, among which, 12 were up-regulated, consisting of gelsolin isoform b and neurite growth-related protein collapsing response mediator protein 2. Western blot analysis showed that gelsolin isoform b was up-regulated at days 7-21 of motion treatment. These findings suggest that active Achilles tendon kinesitherapy promotes the neurite regeneration of a ruptured Achilles tendon and gelsolin isoform b can be used as a biomarker for Achilles tendon healing after kinesitherapy. PMID:25317130

  9. Versican V1 Isoform Induces Neuronal Differentiation and Promotes Neurite Outgrowth

    PubMed Central

    Wu, Yaojiong; Sheng, Wang; Chen, Liwen; Dong, Haiheng; Lee, Vivian; Lu, Fred; Wong, C. Shun; Lu, Wei-Yang; Yang, Burton B.

    2004-01-01

    The chondroitin sulfate proteoglycan versican is one of the major extracellular components in the developing and adult brain. Here, we show that isoforms of versican play different roles in neuronal differentiation and neurite outgrowth. Expression of versican V1 isoform in PC12 cells induced complete differentiation, whereas expression of V2 induced an aborted differentiation accompanied by apoptosis. V1 promoted neurite outgrowth of hippocampal neurons, but V2 failed to do so. V1 transfection enhanced expression of epidermal growth factor receptor and integrins, and facilitated sustained extracellular signal-regulated kinase/MAPK phosphorylation. Blockade of the epidermal growth factor receptor, β1 integrin, or Src significantly inhibited neuronal differentiation. Finally, we demonstrated that versican V1 isoform also promoted differentiation of neural stem cells into neurons. Our results have implications for understanding how versican regulates neuronal development, function, and repair. PMID:14978219

  10. G12V Kras mutations in cervical cancer under virtual microscope of molecular dynamics simulations.

    PubMed

    Chen, X P; Xu, W H; Xu, D F; Fu, S M; Ma, Z C

    2016-01-01

    Kras mutations and cancers are common and their role in the progression of cancer is well known and elucidated. The present work is searching for the most deleterious mutation of the four found at codon 12 and 13 of Kras in cervical cancers using prediction servers; different servers were used to look into different factors that govern the protein function. The in silico results predicted G12V to be the most devastating; this particular mutation was then subjected to molecular dynamics simulation (MDS) for further analysis. The authors' approach of MDSs helped them to place the native and mutant structure under virtual microscope and observe their dynamics over time. The results generated are enlightening the effect of G12V variation on the dynamics of Kras. The structural variation between the native and mutant Kras over 50 nanoseconds (ns) run varied at every parameter checked and the results are in excellent agreement with the available experimental data. PMID:27048113

  11. Ultrafast dynamics of ligand and substrate interaction in endothelial nitric oxide synthase under Soret excitation.

    PubMed

    Hung, Chih-Chang; Yabushita, Atsushi; Kobayashi, Takayoshi; Chen, Pei-Feng; Liang, Keng S

    2016-01-01

    Ultrafast transient absorption spectroscopy of endothelial NOS oxygenase domain (eNOS-oxy) was performed to study dynamics of ligand or substrate interaction under Soret band excitation. Photo-excitation dissociates imidazole ligand in <300fs, then followed by vibrational cooling and recombination within 2ps. Such impulsive bond breaking and late rebinding generate proteinquakes, which relaxes in several tens of picoseconds. The photo excited dynamics of eNOS-oxy with L-arginine substrate mainly occurs at the local site of heme, including ultrafast internal conversion within 400fs, vibrational cooling, charge transfer, and complete ground-state recovery within 1.4ps. The eNOS-oxy without additive is partially bound with water molecule, thus its photoexcited dynamics also shows ligand dissociation in <800fs. Then it followed by vibrational cooling coupled with charge transfer in 4.8ps, and recombination of ligand to distal side of heme in 12ps. PMID:27183248

  12. A Neural Network Model to Learn Multiple Tasks under Dynamic Environments

    NASA Astrophysics Data System (ADS)

    Tsumori, Kenji; Ozawa, Seiichi

    When environments are dynamically changed for agents, the knowledge acquired in an environment might be useless in future. In such dynamic environments, agents should be able to not only acquire new knowledge but also modify old knowledge in learning. However, modifying all knowledge acquired before is not efficient because the knowledge once acquired may be useful again when similar environment reappears and some knowledge can be shared among different environments. To learn efficiently in such environments, we propose a neural network model that consists of the following modules: resource allocating network, long-term & short-term memory, and environment change detector. We evaluate the model under a class of dynamic environments where multiple function approximation tasks are sequentially given. The experimental results demonstrate that the proposed model possesses stable incremental learning, accurate environmental change detection, proper association and recall of old knowledge, and efficient knowledge transfer.

  13. An experimental and mathematical analysis of lymphopoiesis dynamics under continuous irradiation

    SciTech Connect

    Zukhbaya, T.M.; Smirnova, O.A. )

    1991-07-01

    A mathematical model describing the dynamics of lymphopoiesis in mammals continuously exposed to ionizing radiation has been developed. It is based on the theory of chalone regulation of hematopoiesis. The model comprises a system of nine differential equations. Results from the model were compared with our experimental data for bone marrow and blood lymphocytes of rats continuously exposed to gamma radiation in a wide range of dose rates. The model reproduces the lymphopoiesis dynamics that we observed in our experiment, in particular, the radiation hormesis at low dose rates, the reduction of lymphopoiesis at intermediate dose rates, and extinction of lymphopoiesis at high dose rates of continuous radiation. The possible explanation of the hormesis is suggested by the framework of the model. The model can be used for predicting the lymphopoiesis dynamics in mammals under continuous irradiation.

  14. XPCS study of dynamic correlation in polyurethane gel-carbonyl iron composite under magnetic field

    NASA Astrophysics Data System (ADS)

    Grigoriew, Helena; Wiegart, Lutz; Boczkowska, Anna; Mirkowska, Monika

    2010-10-01

    An X-ray photon correlation spectroscopy (XPCS) study of composite-type material consisting of polyurethane gel and carbonyl iron micrometric spheres was performed under magnetic fields of 0, 300 and 600 mT. The onion-like spheres structure was destroyed during the composite processing. The following conclusions were obtained from the study: -The polyurethane matrix is preferred as a source for the observed dynamic effects. -Below 300mT the material dynamics in direction of the outer magnetic field are very clear. -For 600 mT the dependence of the dynamics on magnetic field direction disappears, but the correlation rate is much higher. These findings may be caused by a disturbance of the polymer mesostructure by larger strain leading to its cross-linking.

  15. 5-Hydroxytryptamine 1A and 2B serotonin receptors in neurite outgrowth: involvement of early growth response protein 1.

    PubMed

    Anelli, Tonino; Cardarelli, Silvia; Ori, Michela; Nardi, Irma; Biagioni, Stefano; Poiana, Giancarlo

    2013-01-01

    Neurotransmitters play important roles in neurogenesis; in particular, acetylcholine and serotonin may regulate neurite elongation. Acetylcholine may also activate transcription factors such as early growth response protein 1 (EGR-1), which plays a role in neurite extension. N18TG2 neuroblastoma cells (which do not produce neurotransmitters and constitutively express muscarinic acetylcholine receptors) were transfected with constructs containing the cDNA for choline acetyltransferase, 5-hydroxytryptamine 1A (5-HT1A) and 5-HT2B serotonin receptors to study acetylcholine and serotonin interplay in neurite outgrowth. 5-HT1A receptor stimulation causes a decrease in EGR-1 levels and inhibition of neurite outgrowth; 5-HT2B stimulation, however, has no effect. Muscarinic cholinergic stimulation, on the other end, increases EGR-1 levels and fiber outgrowth. Inhibition of EGR-1 binding reduces fiber outgrowth activity. When both cholinergic and 5-HT1A receptors are stimulated, fiber outgrowth is restored; therefore, acetylcholine counterbalances the inhibitory effect of serotonin on neurite outgrowth. These results suggest that EGR-1 plays a role in the interplay of acetylcholine and serotonin in the regulation of neurite extension during development. PMID:24158140

  16. Olanzapine Prevents the PCP-induced Reduction in the Neurite Outgrowth of Prefrontal Cortical Neurons via NRG1.

    PubMed

    Zhang, Qingsheng; Yu, Yinghua; Huang, Xu-Feng

    2016-01-01

    Accumulating evidence suggests that reducing neurite outgrowth and synaptic plasticity plays a critical role in the pathology of cognitive deficits in schizophrenia. The N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) can induce symptoms of schizophrenia as well as reduce dendritic spine density and neurite growth. The antipsychotic drug olanzapine may improve these deficits. This study aimed to investigate: (1) if olanzapine prevents PCP-induced suppression of neurite outgrowth and synaptic protein expression; (2) if olanzapine affects the Akt-GSK3 signaling pathway; and (3) the role of neuregulin 1 (NRG1) in this process. Immunofluorescence revealed that PCP treatment for 24 hours reduces both neurite length (28.5%) and the number of neurite branches (35.6%) in primary prefrontal cortical neuron cultures. PCP reduced protein and mRNA expressions of synaptophysin (24.9% and 23.2%, respectively) and PSD95 (31.5% and 21.4%, respectively), and the protein expression of p-Akt (26.7%) and p-GSK3β (35.2%). Olanzapine co-treatment prevented these PCP-induced effects in normal neurons but not in neurons from NRG1-knockout mice. These results indicate that NRG1 mediates the preventive effects of olanzapine on the PCP-induced impairment of neurite outgrowth and synaptic protein expression. This study provides potential targets for interventions on improving the efficacy of olanzapine on preventing cognitive deficits in schizophrenia. PMID:26781398

  17. Olanzapine Prevents the PCP-induced Reduction in the Neurite Outgrowth of Prefrontal Cortical Neurons via NRG1

    PubMed Central

    Zhang, Qingsheng; Yu, Yinghua; Huang, Xu-Feng

    2016-01-01

    Accumulating evidence suggests that reducing neurite outgrowth and synaptic plasticity plays a critical role in the pathology of cognitive deficits in schizophrenia. The N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) can induce symptoms of schizophrenia as well as reduce dendritic spine density and neurite growth. The antipsychotic drug olanzapine may improve these deficits. This study aimed to investigate: (1) if olanzapine prevents PCP-induced suppression of neurite outgrowth and synaptic protein expression; (2) if olanzapine affects the Akt-GSK3 signaling pathway; and (3) the role of neuregulin 1 (NRG1) in this process. Immunofluorescence revealed that PCP treatment for 24 hours reduces both neurite length (28.5%) and the number of neurite branches (35.6%) in primary prefrontal cortical neuron cultures. PCP reduced protein and mRNA expressions of synaptophysin (24.9% and 23.2%, respectively) and PSD95 (31.5% and 21.4%, respectively), and the protein expression of p-Akt (26.7%) and p-GSK3β (35.2%). Olanzapine co-treatment prevented these PCP-induced effects in normal neurons but not in neurons from NRG1-knockout mice. These results indicate that NRG1 mediates the preventive effects of olanzapine on the PCP-induced impairment of neurite outgrowth and synaptic protein expression. This study provides potential targets for interventions on improving the efficacy of olanzapine on preventing cognitive deficits in schizophrenia. PMID:26781398

  18. Microtopographical features generated by photopolymerization recruit RhoA/ROCK through TRPV1 to direct cell and neurite growth

    PubMed Central

    Li, Shufeng; Tuft, Bradley; Xu, Linjing; Polacco, Marc; Clarke, Joseph C.; Guymon, C. Allan; Hansen, Marlan R.

    2015-01-01

    Cell processes, including growth cones, respond to biophysical cues in their microenvironment to establish functional tissue architecture and intercellular networks. The mechanisms by which cells sense and translate biophysical cues into directed growth are unknown. We used photopolymerization to fabricate methacrylate platforms with patterned microtopographical features that precisely guide neurite growth and Schwann cell alignment. Pharmacologic inhibition of the transient receptor potential cation channel subfamily V member 1 (TRPV1) or reduced expression of TRPV1 by RNAi significantly disrupts neurite guidance by these microtopographical features. Exogenous expression of TRPV1 induces alignment of NIH3T3 fibroblasts that fail to align in the absence of TRPV1, further implicating TRPV1 channels as critical mediators of cellular responses to biophysical cues. Microtopographic features increase RhoA activity in growth cones and in TRPV1-expressing NIH3T3 cells. Further, Rho-associated kinase (ROCK) phosphorylation is elevated in growth cones and neurites on micropatterned surfaces. Inhibition of RhoA/ROCK by pharmacological compounds or reduced expression of either ROCKI or ROCKII isoforms by RNAi abolishes neurite and cell alignment, confirming that RhoA/ROCK signaling mediates neurite and cell alignment to microtopographic features. These studies demonstrate that microtopographical cues recruit TRPV1 channels and downstream signaling pathways, including RhoA and ROCK, to direct neurite and cell growth. PMID:25890710

  19. State diagram for adhesion dynamics of deformable capsules under shear flow.

    PubMed

    Luo, Zheng Yuan; Bai, Bo Feng

    2016-08-17

    Due to the significance of understanding the underlying mechanisms of cell adhesion in biological processes and cell capture in biomedical applications, we numerically investigate the adhesion dynamics of deformable capsules under shear flow by using a three-dimensional computational fluid dynamic model. This model is based on the coupling of the front tracking-finite element method for elastic mechanics of the capsule membrane and the adhesion kinetics simulation for adhesive interactions between capsules and functionalized surfaces. Using this model, three distinct adhesion dynamic states are predicted, such as detachment, rolling and firm-adhesion. Specifically, the effects of capsule deformability quantified by the capillary number on the transitions of these three dynamic states are investigated by developing an adhesion dynamic state diagram for the first time. At low capillary numbers (e.g. Ca < 0.0075), whole-capsule deformation confers the capsule a flattened bottom in contact with the functionalized surface, which hence promotes the rolling-to-firm-adhesion transition. It is consistent with the observations from previous studies that cell deformation promotes the adhesion of cells lying in the rolling regime. However, it is surprising to find that, at relatively high capillary numbers (e.g. 0.0075 < Ca < 0.0175), the effect of capsule deformability on its adhesion dynamics is far more complex than just promoting adhesion. High deformability of capsules makes their bottom take a concave shape with no adhesion bond formation in the middle. The appearance of this specific capsule shape inhibits the transitions of both rolling-to-firm-adhesion and detachment-to-rolling, and it means that capsule deformation no longer promotes the capsule adhesion. Besides, it is interesting to note that, when the capillary number exceeds a critical value (e.g. Ca = 0.0175), the rolling state no longer appears, since capsules exhibit large deviation from the spherical shape

  20. Cyclic AMP Stimulates Neurite Outgrowth of Lamprey Reticulospinal Neurons without Substantially Altering Their Biophysical Properties

    PubMed Central

    Pale, Timothée; Frisch, Emily B.; McClellan, Andrew D.

    2013-01-01

    Reticulospinal (RS) neurons are critical for initiation of locomotor behavior, and following spinal cord injury (SCI) in the lamprey, the axons of these neurons regenerate and restore locomotor behavior within a few weeks. For lamprey RS neurons in culture, experimental induction of calcium influx, either in the growth cone or cell body, is inhibitory for neurite outgrowth. Following SCI, these neurons partially downregulate calcium channel expression, which would be expected to reduce calcium influx and possibly provide supportive conditions for axonal regeneration. In the present study, it was tested whether activation of second messenger signaling pathways stimulates neurite outgrowth of lamprey RS neurons without altering their electrical properties (e.g. spike broadening) so as to possibly increase calcium influx and compromise axonal growth. First, activation of cAMP pathways with forskolin or dbcAMP stimulated neurite outgrowth of RS neurons in culture in a PKA-dependent manner, while activation of cGMP signaling pathways with dbcGMP inhibited outgrowth. Second, neurophysiological recordings from uninjured RS neurons in isolated lamprey brain-spinal cord preparations indicated that dbcAMP or dbcGMP did not significantly affect any of the measured electrical properties. In contrast, for uninjured RS neurons, forskolin increased action potential duration, which might have increased calcium influx, but did not significantly affect most other electrical properties. Importantly, for injured RS neurons during the period of axonal regeneration, forskolin did not significantly alter their electrical properties. Taken together, these results suggest that activation of cAMP signaling by dbcAMP stimulates neurite outgrowth, but does not alter the electrical properties of lamprey RS neurons in such a way that would be expected to induce calcium influx. In conclusion, our results suggest that activation of cAMP pathways alone, without compensation for possible

  1. Influence of micro-patterned PLLA membranes on outgrowth and orientation of hippocampal neurites.

    PubMed

    Morelli, Sabrina; Salerno, Simona; Piscioneri, Antonella; Papenburg, Bernke J; Di Vito, Anna; Giusi, Giuseppina; Canonaco, Marcello; Stamatialis, Dimitrios; Drioli, Enrico; De Bartolo, Loredana

    2010-09-01

    In neuronal tissue engineering many efforts are focused on creating biomaterials with physical and chemical pathways for controlling cellular proliferation and orientation. Neurons have the ability to respond to topographical features in their microenvironment causing among others, axons to proliferate along surface features such as substrate grooves in micro-and nanoscales. As a consequence these neuronal elements are able to correctly adhere, migrate and orient within their new environment during growth. Here we explored the polarization and orientation of hippocampal neuronal cells on nonpatterned and micro-patterned biodegradable poly(l-lactic acid) (PLLA) membranes with highly selective permeable properties. Dense and porous nonpatterned and micro-patterned membranes were prepared from PLLA by Phase Separation Micromolding. The micro-patterned membranes have a three-dimensional structure consisting of channels and ridges and of bricks of different widths. Nonpatterned and patterned membranes were used for hippocampal neuronal cultures isolated from postnatal days 1-3 hamsters and the neurite length, orientation and specific functions of cells were investigated up to 12 days of culture. Neurite outgrowth, length plus orientation tightly overlapped the pattern of the membrane surface. Cell distribution occurred only in correspondence to membrane grooves characterized by continuous channels whereas on membranes with interconnected channels, cells not only adhered to and elongated their cellular processes in the grooves but also in the breaking points. High orientation degrees of cells were determined particularly on the patterned porous membranes with channel width of 20 mum and ridges of 17 mum whereas on dense nonpatterned membranes as well as on polystyrene culture dish (PSCD) controls, a larger number of primary developed neurites were distributed. Based on these results, PLLA patterned membranes may directly improve the guidance of neurite extension and

  2. Regulation of Neurite Growth by Inorganic Pyrophosphatase 1 via JNK Dephosphorylation

    PubMed Central

    Tezuka, Yu; Okada, Mizuki; Tada, Yuka; Yamauchi, Junji; Nishigori, Hideo; Sanbe, Atsushi

    2013-01-01

    Neural cell differentiation during development is controlled by multiple signaling pathways, in which protein phosphorylation and dephosphorylation play an important role. In this study, we examined the role of pyrophosphatase1 (PPA1) in neuronal differentiation using the loss and gain of function analysis. Neuronal differentiation induced by external factors was studied using a mouse neuroblastoma cell line (N1E115). The neuronal like differentiation in N1E115 cells was determined by morphological analysis based on neurite growth length. In order to analyze the loss of the PPA1 function in N1E115, si-RNA specifically targeting PPA1 was generated. To study the effect of PPA1 overexpression, an adenoviral gene vector containing the PPA1 gene was utilized to infect N1E115 cells. To address the need for pyrophosphatase activity in PPA1, D117A PPA1, which has inactive pyrophosphatase, was overexpressed in N1E115 cells. We used valproic acid (VPA) as a neuronal differentiator to examine the effect of PPA1 in actively differentiated N1E115 cells. Si-PPA1 treatment reduced the PPA1 protein level and led to enhanced neurite growth in N1E115 cells. In contrast, PPA1 overexpression suppressed neurite growth in N1E115 cells treated with VPA, whereas this effect was abolished in D117A PPA1. PPA1 knockdown enhanced the JNK phosphorylation level, and PPA1 overexpression suppressed it in N1E115 cells. It seems that recombinant PPA1 can dephosphorylate JNK while no alteration of JNK phosphorylation level was seen after treatment with recombinant PPA1 D117A. Enhanced neurite growth by PPA1 knockdown was also observed in rat cortical neurons. Thus, PPA1 may play a role in neuronal differentiation via JNK dephosphorylation. PMID:23626709

  3. Kalirin is required for BDNF-TrkB stimulated neurite outgrowth and branching.

    PubMed

    Yan, Yan; Eipper, Betty A; Mains, Richard E

    2016-08-01

    Exogenous brain-derived neurotrophic factor (BDNF), acting through TrkB, is known to promote neurite formation and branching. This response to BDNF was eliminated by inhibition of TrkB kinase and by specific inhibition of the GEF1 domain of Kalirin, which activates Rac1. Neurons from Kalrn knockout mice were unable to activate Rac1 in response to BDNF. BDNF-triggered neurite outgrowth was abolished when Kalrn expression was reduced using shRNA that targets all of the major Kalrn isoforms, and reduced in neurons from Kalrn knockout mice. The Kalrn isoforms expressed early in development also include a GEF2 domain that activates RhoA. However, BDNF-stimulated neurite outgrowth in Kalrn knockout neurons was rescued by expression of Kalirin-7, which includes only the GEF1 domain but lacks the GEF2 domain. Dendritic morphogenesis, which requires spatially restricted, coordinated changes in the actin cytoskeleton and in the organization of microtubules, involves essential contributions from multiple Rho GEFs. Since Tiam1, another Rho GEF, is also required for BDNF-stimulated neurite outgrowth, an inhibitory fragment of Tiam1 (PHn-CC-EX) was tested and found to interfere with both Kalirin and Tiam1 GEF activity. The prolonged TrkB activation observed in response to BDNF in Kalrn knockout neurons and the altered time course and extent of ERK, CREB and Akt activation observed in the absence of Kalrn would be expected to alter the response of these neurons to other regulatory factors. PMID:27036892

  4. Knockdown of pre-mRNA cleavage factor Im 25 kDa promotes neurite outgrowth

    SciTech Connect

    Fukumitsu, Hidefumi; Soumiya, Hitomi; Furukawa, Shoei

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer CFIm25 knockdown promoted NGF-induced neurite out growth from PC12 cells. Black-Right-Pointing-Pointer Depletion of CFIm25 did not influence the morphology of proliferating PC12 cells. Black-Right-Pointing-Pointer CFIm regulated NGF-induced neurite outgrowth via coordinating RhoA activity. Black-Right-Pointing-Pointer CFIm25 knockdown increase the number of primary dendrites of hippocampal neurons. -- Abstract: Mammalian precursor mRNA (pre-mRNA) cleavage factor I (CFIm) plays important roles in the selection of poly(A) sites in a 3 Prime -untranslated region (3 Prime -UTR), producing mRNAs with variable 3 Prime ends. Because 3 Prime -UTRs often contain cis elements that impact stability or localization of mRNA or translation, alternative polyadenylation diversifies utilization of primary transcripts in mammalian cells. However, the physiological role of CFIm remains unclear. CFIm acts as a heterodimer comprising a 25 kDa subunit (CFIm25) and one of the three large subunits-CFIm59, CFIm68, or CFIm72. CFIm25 binds directly to RNA and introduces and anchors the larger subunit. To examine the physiological roles of CFIm, we knocked down the CFIm25 gene in neuronal cells using RNA interference. Knockdown of CFIm25 increased the number of primary dendrites of developing hippocampal neurons and promoted nerve growth factor (NGF)-induced neurite extension from rat pheochromocytoma PC12 cells without affecting the morphology of proliferating PC12 cells. On the other hand, CFIm25 knockdown did not influence constitutively active or dominantly negative RhoA suppression or promotion of NGF-induced neurite extension from PC12 cells, respectively. Taken together, our results indicate that endogenous CFIm may promote neuritogenesis in developing neurons by coordinating events upstream of NGF-induced RhoA inactivation.

  5. Induction of neurite outgrowth in 3D hydrogel-based environments.

    PubMed

    Assunção-Silva, Rita C; Oliveira, Cátia Costa; Ziv-Polat, Ofra; Gomes, Eduardo D; Sahar, Abraham; Sousa, Nuno; Silva, Nuno A; Salgado, António J

    2015-09-01

    The ability of peripheral nervous system (PNS) axons to regenerate and re-innervate their targets after an injury has been widely recognized. However, despite the considerable advances made in microsurgical techniques, complete functional recovery is rarely achieved, especially for severe peripheral nerve injuries (PNIs). Therefore, alternative therapies that can successfully repair peripheral nerves are still essential. In recent years the use of biodegradable hydrogels enriched with growth-supporting and guidance cues, cell transplantation, and biomolecular therapies have been explored for the treatment of PNIs. Bearing this in mind, the aim of this study was to assess whether Gly-Arg-Gly-Asp-Ser synthetic peptide (GRGDS)-modified gellan gum (GG) based hydrogels could foster an amenable environment for neurite/axonal growth. Additionally, strategies to further improve the rate of neurite outgrowth were also tested, namely the use of adipose tissue derived stem cells (ASCs), as well as the glial derived neurotrophic factor (GDNF). In order to increase its stability and enhance its bioactivity, the GDNF was conjugated covalently to iron oxide nanoparticles (IONPs). The impact of hydrogel modification as well as the effect of the GDNF-IONPs on ASC behavior was also screened. The results revealed that the GRGDS-GG hydrogel was able to support dorsal root ganglia (DRG)-based neurite outgrowth, which was not observed for non-modified hydrogels. Moreover, the modified hydrogels were also able to support ASCs attachment. In contrast, the presence of the GDNF-IONPs had no positive or negative impact on ASC behavior. Further experiments revealed that the presence of ASCs in the hydrogel improved axonal growth. On the other hand, GDNF-IONPs alone or combined with ASCs significantly increased neurite outgrowth from DRGs, suggesting a beneficial role of the proposed strategy for future applications in PNI regenerative medicine. PMID:26480959

  6. A dynamic programming-based particle swarm optimization algorithm for an inventory management problem under uncertainty

    NASA Astrophysics Data System (ADS)

    Xu, Jiuping; Zeng, Ziqiang; Han, Bernard; Lei, Xiao

    2013-07-01

    This article presents a dynamic programming-based particle swarm optimization (DP-based PSO) algorithm for solving an inventory management problem for large-scale construction projects under a fuzzy random environment. By taking into account the purchasing behaviour and strategy under rules of international bidding, a multi-objective fuzzy random dynamic programming model is constructed. To deal with the uncertainties, a hybrid crisp approach is used to transform fuzzy random parameters into fuzzy variables that are subsequently defuzzified by using an expected value operator with optimistic-pessimistic index. The iterative nature of the authors' model motivates them to develop a DP-based PSO algorithm. More specifically, their approach treats the state variables as hidden parameters. This in turn eliminates many redundant feasibility checks during initialization and particle updates at each iteration. Results and sensitivity analysis are presented to highlight the performance of the authors' optimization method, which is very effective as compared to the standard PSO algorithm.

  7. Dynamical instability induced by the zero mode under symmetry breaking external perturbation

    NASA Astrophysics Data System (ADS)

    Takahashi, J.; Nakamura, Y.; Yamanaka, Y.

    2014-08-01

    A complex eigenvalue in the Bogoliubov-de Gennes equations for a stationary Bose-Einstein condensate in the ultracold atomic system indicates the dynamical instability of the system. We also have the modes with zero eigenvalues for the condensate, called the zero modes, which originate from the spontaneous breakdown of symmetries. Although the zero modes are suppressed in many theoretical analyses, we take account of them in this paper and argue that a zero mode can change into one with a pure imaginary eigenvalue by applying a symmetry breaking external perturbation potential. This emergence of a pure imaginary mode adds a new type of scenario of dynamical instability to that characterized by the complex eigenvalue of the usual excitation modes. For illustration, we deal with two one-dimensional homogeneous Bose-Einstein condensate systems with a single dark soliton under a respective perturbation potential, breaking the invariance under translation, to derive pure imaginary modes.

  8. Modeling and Characterization of Dynamic Failure of Soda-lime Glass Under High Speed Impact

    SciTech Connect

    Liu, Wenning N.; Sun, Xin; Chen, Weinong W.; Templeton, Douglas W.

    2012-05-27

    In this paper, the impact-induced dynamic failure of a soda-lime glass block is studied using an integrated experimental/analytical approach. The Split Hopkinson Pressure Bar (SHPB) technique is used to conduct dynamic failure test of soda-lime glass first. The damage growth patterns and stress histories are reported for various glass specimen designs. Making use of a continuum damage mechanics (CDM)-based constitutive model, the initial failure and subsequent stiffness reduction of glass are simulated and investigated. Explicit finite element analyses are used to simulate the glass specimen impact event. A maximum shear stress-based damage evolution law is used in describing the glass damage process under combined compression/shear loading. The impact test results are used to quantify the critical shear stress for the soda-lime glass under examination.

  9. Dynamics of Freely Oscillating and Coupled Hair Cell Bundles under Mechanical Deflection

    PubMed Central

    Fredrickson-Hemsing, Lea; Strimbu, C. Elliott; Roongthumskul, Yuttana; Bozovic, Dolores

    2012-01-01

    In vitro, attachment to the overlying membrane was found to affect the resting position of the hair cell bundles of the bullfrog sacculus. To assess the effects of such a deflection on mechanically decoupled hair bundles, comparable offsets were imposed on decoupled spontaneously oscillating bundles. Strong modulation was observed in their dynamic state under deflection, with qualitative changes in the oscillation profile, amplitude, and characteristic frequency of oscillation seen in response to stimulus. Large offsets were found to arrest spontaneous oscillation, with subsequent recovery upon reversal of the stimulus. The dynamic state of the hair bundle displayed hysteresis and a dependence on the direction of the imposed offset. The coupled system of hair bundles, with the overlying membrane left on top of the preparation, also exhibited a dependence on offset position, with an increase in the linear response function observed under deflections in the inhibitory direction. PMID:22768934

  10. Dynamics of freely oscillating and coupled hair cell bundles under mechanical deflection.

    PubMed

    Fredrickson-Hemsing, Lea; Strimbu, C Elliott; Roongthumskul, Yuttana; Bozovic, Dolores

    2012-04-18

    In vitro, attachment to the overlying membrane was found to affect the resting position of the hair cell bundles of the bullfrog sacculus. To assess the effects of such a deflection on mechanically decoupled hair bundles, comparable offsets were imposed on decoupled spontaneously oscillating bundles. Strong modulation was observed in their dynamic state under deflection, with qualitative changes in the oscillation profile, amplitude, and characteristic frequency of oscillation seen in response to stimulus. Large offsets were found to arrest spontaneous oscillation, with subsequent recovery upon reversal of the stimulus. The dynamic state of the hair bundle displayed hysteresis and a dependence on the direction of the imposed offset. The coupled system of hair bundles, with the overlying membrane left on top of the preparation, also exhibited a dependence on offset position, with an increase in the linear response function observed under deflections in the inhibitory direction. PMID:22768934

  11. Kinematic model for the space-variant image motion of star sensors under dynamical conditions

    NASA Astrophysics Data System (ADS)

    Liu, Chao-Shan; Hu, Lai-Hong; Liu, Guang-Bin; Yang, Bo; Li, Ai-Jun

    2015-06-01

    A kinematic description of a star spot in the focal plane is presented for star sensors under dynamical conditions, which involves all necessary parameters such as the image motion, velocity, and attitude parameters of the vehicle. Stars at different locations of the focal plane correspond to the slightly different orientation and extent of motion blur, which characterize the space-variant point spread function. Finally, the image motion, the energy distribution, and centroid extraction are numerically investigated using the kinematic model under dynamic conditions. A centroid error of eight successive iterations <0.002 pixel is used as the termination criterion for the Richardson-Lucy deconvolution algorithm. The kinematic model of a star sensor is useful for evaluating the compensation algorithms of motion-blurred images.

  12. The dynamical mechanical properties of tungsten under compression at working temperature range of divertors

    NASA Astrophysics Data System (ADS)

    Zhu, C. C.; Song, Y. T.; Peng, X. B.; Wei, Y. P.; Mao, X.; Li, W. X.; Qian, X. Y.

    2016-02-01

    In the divertor structure of ITER and EAST with mono-block module, tungsten plays not only a role of armor material but also a role of structural material, because electromagnetic (EM) impact will be exerted on tungsten components in VDEs or CQ. The EM loads can reach to 100 MN, which would cause high strain rates. In addition, directly exposed to high-temperature plasma, the temperature regime of divertor components is complex. Aiming at studying dynamical response of tungsten divertors under EM loads, an experiment on tungsten employed in EAST divertors was performed using a Kolsky bar system. The testing strain rates and temperatures is derived from actual working conditions, which makes the constitutive equation concluded by using John-Cook model and testing data very accurate and practical. The work would give a guidance to estimate the dynamical response, fatigue life and damage evolution of tungsten divertor components under EM impact loads.

  13. Hopkinson pressure bar set-up for the measurement of Bauschinger effect under dynamic loading

    NASA Astrophysics Data System (ADS)

    Ruggiero, Andrew; Bonora, Nicola; Iannitti, Gianluca

    2013-06-01

    Metals and alloys show different stress-strain characteristics under reverse loading cycle (Bauschinger effect). The knowledge of the effective material response is important in impact dynamics where material is subjected to compression-tension loading as a result of stress wave propagation. In this paper an experimental set-up of the Hopkinson pressure bar to characterize the material response under dynamic loading cycle is presented. In the proposed configuration, in one single test, the sample is subjected to tension and compression loading with same absolute stress intensity and duration. Also this solution allows the possibility to select the load cycle sequence (tension-compression or compression-tension). Relationships to determine the stress, strain rate and strain from the elastic signals at the bars which are also effective for the second stress pulse, are presented. The method was verified with FEM and used to determine the Bauschinger effect for AISI 316L stainless steel.

  14. A NASTRAN DMAP alter for linear buckling analysis under dynamic loading

    NASA Technical Reports Server (NTRS)

    Aiello, Robert A.; Grady, Joseph E.

    1988-01-01

    A unique modification to the NASTRAN solution sequence for transient analysis with direct time integration (COSMIC NASTRAN rigid format 9) was developed and incorporated into a DMAP alter. This DMAP alter calculates the buckling stability of a dynamically loaded structure, and is used to predict the onset of structural buckling under stress wave loading conditions. The modified solution sequence incorporates the linear buckling analysis capability (rigid format 5) of NASTRAN into the existing Transient solution rigid format in such a way as to provide a time dependent eigensolution which is used to assess the buckling stability of the structure as it responds to the impulsive load. As a demonstration of the validity of this modified solution procedure, the dynamic buckling of a prismatic bar subjected to an impulsive longitudinal compression is analyzed and compared to the known theoretical solution. In addition, a dynamic buckling analysis is performed for the analytically less tractable problem of the localized dynamic buckling of an initially flawed composite laminate under transverse impact loading. The addition of this DMAP alter to the transient solution sequence in NASTRAN facilitates the prediction of both time and mode of buckling.

  15. [Dynamic changes of soil ecological factors in Ziwuling secondary forest area under human disturbance].

    PubMed

    Zhou, Zhengchao; Shangguan, Zhouping

    2005-09-01

    As a widespread natural phenomenon, disturbance is considered as a discrete event occurred in natural ecosystems at various spatial and temporal scales. The occurrence of disturbance directly affects the structure, function and dynamics of ecosystems. Forest logging and forestland assart, the common human disturbances in forest area, have caused the dynamic changes of forest soil ecological factors in a relatively consistent environment. A study on the dynamics of soil bulk density, soil organic matter, soil microbes and other soil ecological factors under different human disturbance (logging and assart, logging but without assart, control) were conducted in the Ziwuling secondary forest area. The results indicated that human disturbance had a deep impact on the soil ecological factors, with soil physical and chemical properties become bad, soil organic matter decreased from 2.2% to 0.8%, and soil stable aggregates dropped more than 30%. The quantity of soil microbes decreased sharply with enhanced human disturbance. Soil organic matter and soil microbes decreased more than 50% and 90%, respectively, and soil bulk density increased from 0.9 to 1.21 g x cm(-3) with increasing soil depth. Ditch edge level also affected the dynamics of soil factors under the same disturbance, with a better soil ecological condition at low-than at high ditch edge level. PMID:16355766

  16. The optimal dynamic immunization under a controlled heterogeneous node-based SIRS model

    NASA Astrophysics Data System (ADS)

    Yang, Lu-Xing; Draief, Moez; Yang, Xiaofan

    2016-05-01

    Dynamic immunizations, under which the state of the propagation network of electronic viruses can be changed by adjusting the control measures, are regarded as an alternative to static immunizations. This paper addresses the optimal dynamical immunization under the widely accepted SIRS assumption. First, based on a controlled heterogeneous node-based SIRS model, an optimal control problem capturing the optimal dynamical immunization is formulated. Second, the existence of an optimal dynamical immunization scheme is shown, and the corresponding optimality system is derived. Next, some numerical examples are given to show that an optimal immunization strategy can be worked out by numerically solving the optimality system, from which it is found that the network topology has a complex impact on the optimal immunization strategy. Finally, the difference between a payoff and the minimum payoff is estimated in terms of the deviation of the corresponding immunization strategy from the optimal immunization strategy. The proposed optimal immunization scheme is justified, because it can achieve a low level of infections at a low cost.

  17. Identification of explosive media using spectrum dynamics under the action of a THz pulse

    NASA Astrophysics Data System (ADS)

    Trofimov, Vyacheslav A.; Varentsova, Svetlana A.; Chen, Jian; Zhang, Xi-Cheng

    2009-09-01

    A method of THz spectral dynamics analysis (SDA) of medium response in the THz and GHz ranges, which was developed by us in previous papers for detection and identification of materials, is used for the treatment of experimentally measured signals, passed through selected explosives, including those hidden under covering materials. This technique is based on the window sliding method and on restoration of the THz pulse. It allows researchers to follow the dynamics of many spectral lines in one set of measurements simultaneously and to obtain the full information about the spectrum dynamics of the THz pulse. Relaxation time of rotational transitions, for example, can be determined too. This information gives an opportunity to detect and identify materials despite the similarity in their THz spectra-which may be identical. We show that the spectrum dynamics of THz pulses, passed through the explosives hidden under plastic, cotton and leather barriers-covers, differ widely for these media despite little difference in their spectra. Consequently, our method allows for detection and identification of the hidden explosives with high probability.

  18. On the dynamics underlying the emergence of large scale structures in barotropic beta-plane turbulence

    NASA Astrophysics Data System (ADS)

    Bakas, Nikolaos; Constantinou, Navid; Ioannou, Petros

    2016-04-01

    Planetary turbulent flows are observed to self-organize into large scale structures such as zonal jets and coherent vortices. In this work, the eddy-mean flow dynamics underlying the formation of both zonal and nonzonal coherent structures in a barotropic turbulent flow is investigated within the statistical framework of stochastic structural stability theory (S3T). Previous studies have shown that the coherent structures emerge due to the instability of the homogeneous turbulent flow in the statistical dynamical S3T system and that the statistical predictions of S3T are reflected in direct numerical simulations. In this work, the dynamics underlying this S3T statistical instability are studied. It is shown that, for weak planetary vorticity gradient beta, both zonal jets and non-zonal large-scale structures form from upgradient momentum fluxes due to shearing of the eddies by the emerging flow. For large beta, the dynamics of the S3T instability differs for zonal and non-zonal flows. Shearing of the eddies by the mean flow continues to be the mechanism for the emergence of zonal jets while non-zonal large-scale flows emerge from resonant and near-resonant triad interactions between the large-scale flow and the stochastically forced eddies.

  19. Optimal overlap length in staggered architecture composites under dynamic loading conditions

    NASA Astrophysics Data System (ADS)

    Dutta, Abhishek; Tekalur, Srinivasan Arjun; Miklavcic, Milan

    2013-01-01

    Hybrid staggered architecture composites, like nacre and bone, are known for two discernible aspects: superior strength and synergistic toughness. What is lacking is the scientific rationale proving suitability of these materials under impact/time dependent loading. The current investigation aims to address the structure-property correlationship of these materials by development of an analytical model under dynamic rates of loading. Existing literature studies address behavior of staggered materials under quasi-static loading conditions. Critical overlap length was computed for three natural composites-nacre, spider-silk and, collagen in bone/tendon, and showed reasonable agreement with experimental data. Applicability of the analytical approach to predict lap-joint strength has been briefly discussed and quantified against experimental data. Choice of nanometer sized building blocks in natural composites has been addressed and explained from shear transfer efficiency point of view. The potentiality of these composites for use as biomimetic protective material under impact loading has been addressed as well.

  20. Determination of the elasticity of parachute materials under dynamic loading conditions

    SciTech Connect

    Behr, V.L.; Clements, P.J.; Silbert, M.N.

    1996-12-31

    In the design of parachute systems it is important to use material properties that have been acquired under representative strain rates expected in flight. Without such data the designer is potentially forced to incorporate unrealistic safety margins resulting in a heavier and costlier than required design. Laboratory test data has generally been limited to that which can be acquired at quasi-steady strain rates. This paper investigates a technique, which takes advantage of advances in solid state electronics in the past ten years, to achieve an economical means of acquiring material properties under dynamic strain conditions. Data obtained with this technique is compared to standard test data for representative parachute materials.

  1. Elevated Temperature Slow Crack Growth of Silicon Nitride Under Dynamic, Static and Cyclic Flexural Loading

    NASA Technical Reports Server (NTRS)

    Choi, Sung R.; Salem, Jonathan A.; Nemeth, Noel; Gyekenyesi, John P.

    1994-01-01

    The slow crack growth parameters of a hot-pressed silicon nitride were determined at 1200 and 1300 C in air by statically, dynamically and cyclicly loading bend specimens. The fatigue parameters were estimated using the recently developed CARES/Life computer code. Good agreement exists between the flexural results. However, fatigue susceptibility under static uniaxial tensile loading, reported elsewhere, was greater than in flexure. Cyclic flexural loading resulted in the lowest apparent flexural fatigue susceptibility.

  2. Initial neurite outgrowth in Drosophila neurons is driven by kinesin-powered microtubule sliding

    PubMed Central

    Lu, Wen; Fox, Pangkong; Lakonishok, Margot; Davidson, Michael W.; Gelfand, Vladimir I.

    2013-01-01

    Summary Remarkably, forces within a neuron can extend its axon to a target that could be meters away. The two main cytoskeleton components in neurons are microtubules, which are mostly bundled along the axon shaft, and actin filaments, which are highly enriched in a structure at the axon distal tip, the growth cone. Neurite extension has been thought to be driven by a combination of two forces: pushing via microtubule assembly and/or pulling by an actin-driven mechanism in the growth cone [1, 2]. Here we show that a novel mechanism, sliding of microtubules against each other by the microtubule motor kinesin-1 provides the mechanical forces necessary for initial neurite extension in Drosophila neurons. Neither actin filaments in the growth cone nor tubulin polymerization is required for initial outgrowth. Microtubule sliding in neurons is developmentally regulated and is suppressed during neuronal maturation. As kinesin-1 is highly evolutionarily conserved from Drosophila to humans, it is likely that kinesin-1-powered microtubule sliding plays an important role in neurite extension in many types of neurons across species. PMID:23707427

  3. Automatic Robust Neurite Detection and Morphological Analysis of Neuronal Cell Cultures in High-content Screening

    PubMed Central

    Wu, Chaohong; Schulte, Joost; Sepp, Katharine J.; Littleton, J. Troy

    2011-01-01

    Cell-based high content screening (HCS) is becoming an important and increasingly favored approach in therapeutic drug discovery and functional genomics. In HCS, changes in cellular morphology and biomarker distributions provide an information-rich profile of cellular responses to experimental treatments such as small molecules or gene knockdown probes. One obstacle that currently exists with such cell-based assays is the availability of image processing algorithms that are capable of reliably and automatically analyzing large HCS image sets. HCS images of primary neuronal cell cultures are particularly challenging to analyze due to complex cellular morphology. Here we present a robust method for quantifying and statistically analyzing the morphology of neuronal cells in HCS images. The major advantages of our method over existing software lie in its capability to correct non-uniform illumination using the contrast-limited adaptive histogram equalization method; segment neuromeres using Gabor-wavelet texture analysis; and detect faint neurites by a novel phase-based neurite extraction algorithm that is invariant to changes in illumination and contrast and can accurately localize neurites. Our method was successfully applied to analyze a large HCS image set generated in a morphology screen for polyglutamine-mediated neuronal toxicity using primary neuronal cell cultures derived from embryos of a Drosophila Huntington’s Disease (HD) model. PMID:20405243

  4. Propolis Inhibits Neurite Outgrowth in Differentiating SH-SY5Y Human Neuroblastoma Cells.

    PubMed

    Kim, Han Bit; Yoo, Byung Sun

    2016-07-01

    Propolis is a multicomponent, active, complex resinous substance collected by honeybees from a variety of plant sources. We have studied the effect of propolis on neurite outgrowth of SH-SY5Y human neuroblastoma cells induced to differentiate by all-trans-retinoic acid (RA). Propolis, at a concentration of 3 μg/mL, had no significant effect on the viability of differentiating SH-SY5Y cells. However, the neurite outgrowth of the differentiating SH-SY5Y cells treated with propolis (0.3~3 μg/mL) for 48 hr was significantly inhibited in a dose-dependent manner. Treatment of RA-stimulated differentiating SH-SY5Y cells with 0.3 to 3 μg/mL propolis resulted in decreased level of transglutaminase and 43-kDa growth-associated protein (GAP-43) in a dose-dependent manner. The results indicate that propolis is able to inhibit neurite outgrowth of differentiating SH-SY5Y cells. PMID:27437091

  5. Propolis Inhibits Neurite Outgrowth in Differentiating SH-SY5Y Human Neuroblastoma Cells

    PubMed Central

    Kim, Han Bit; Yoo, Byung Sun

    2016-01-01

    Propolis is a multicomponent, active, complex resinous substance collected by honeybees from a variety of plant sources. We have studied the effect of propolis on neurite outgrowth of SH-SY5Y human neuroblastoma cells induced to differentiate by all-trans-retinoic acid (RA). Propolis, at a concentration of 3 μg/mL, had no significant effect on the viability of differentiating SH-SY5Y cells. However, the neurite outgrowth of the differentiating SH-SY5Y cells treated with propolis (0.3~3 μg/mL) for 48 hr was significantly inhibited in a dose-dependent manner. Treatment of RA-stimulated differentiating SH-SY5Y cells with 0.3 to 3 μg/mL propolis resulted in decreased level of transglutaminase and 43-kDa growth-associated protein (GAP-43) in a dose-dependent manner. The results indicate that propolis is able to inhibit neurite outgrowth of differentiating SH-SY5Y cells. PMID:27437091

  6. Anillin Regulates Neuronal Migration and Neurite Growth by Linking RhoG to the Actin Cytoskeleton.

    PubMed

    Tian, Dong; Diao, Min; Jiang, Yuxiang; Sun, Lingfei; Zhang, Yan; Chen, Zhucheng; Huang, Shanjin; Ou, Guangshuo

    2015-05-01

    Neuronal migration and neurite growth are essential events in neural development, but it remains unclear how guidance cues are transduced through receptors to the actin cytoskeleton, which powers these processes. We report that a cytokinetic scaffold protein, Anillin, is redistributed to the leading edge of the C. elegans Q neuroblast during cell migration and neurite growth. To bypass the requirement for Anillin in cytokinesis, we used the somatic CRISPR-Cas9 technique to generate conditional mutations in Anillin. We demonstrate that Anillin regulates cell migration and growth cone extension by stabilizing the F-actin network at the leading edge. Our biochemical analysis shows that the actin-binding domain of Anillin is sufficient to stabilize F-actin by antagonizing the F-actin severing activity of Cofilin. We further uncover that the active form of RhoG/MIG-2 directly binds to Anillin and recruits it to the leading edge. Our results reveal a novel pathway in which Anillin transduces the RhoG signal to the actin cytoskeleton during neuronal migration and neurite growth. PMID:25843030

  7. Quantifying Spiral Ganglion Neurite and Schwann Behavior on Micropatterned Polymer Substrates.

    PubMed

    Cheng, Elise L; Leigh, Braden; Guymon, C Allan; Hansen, Marlan R

    2016-01-01

    The first successful in vitro experiments on the cochlea were conducted in 1928 by Honor Fell (Fell, Arch Exp Zellforsch 7(1):69-81, 1928). Since then, techniques for culture of this tissue have been refined, and dissociated primary culture of the spiral ganglion has become a widely accepted in vitro model for studying nerve damage and regeneration in the cochlea. Additionally, patterned substrates have been developed that facilitate and direct neural outgrowth. A number of automated and semi-automated methods for quantifying this neurite outgrowth have been utilized in recent years (Zhang et al., J Neurosci Methods 160(1):149-162, 2007; Tapias et al., Neurobiol Dis 54:158-168, 2013). Here, we describe a method to study the effect of topographical cues on spiral ganglion neurite and Schwann cell alignment. We discuss our microfabrication process, characterization of pattern features, cell culture techniques for both spiral ganglion neurons and spiral ganglion Schwann cells. In addition, we describe protocols for reducing fibroblast count, immunocytochemistry, and methods for quantifying neurite and Schwann cell alignment. PMID:27259935

  8. Effects of borate-based bioactive glass on neuron viability and neurite extension.

    PubMed

    Marquardt, Laura M; Day, Delbert; Sakiyama-Elbert, Shelly E; Harkins, Amy B

    2014-08-01

    Bioactive glasses have recently been shown to promote regeneration of soft tissues by positively influencing tissue remodeling during wound healing. We were interested to determine whether bioactive glasses have the potential for use in the treatment of peripheral nerve injury. In these experiments, degradable bioactive borate glass was fabricated into rods and microfibers. To study the compatibility with neurons, embryonic chick dorsal root ganglia (DRG) were cultured with different forms of bioactive borate glass. Cell viability was measured with no media exchange (static condition) or routine media exchange (transient condition). Neurite extension was measured within fibrin scaffolds with embedded glass microfibers or aligned rod sheets. Mixed cultures of neurons, glia, and fibroblasts growing in static conditions with glass rods and microfibers resulted in decreased cell viability. However, the percentage of neurons compared with all cell types increased by the end of the culture protocol compared with culture without glass. Furthermore, bioactive glass and fibrin composite scaffolds promoted neurite extension similar to that of control fibrin scaffolds, suggesting that glass does not have a significant detrimental effect on neuronal health. Aligned glass scaffolds guided neurite extension in an oriented manner. Together these findings suggest that bioactive glass can provide alignment to support directed axon growth. PMID:24027222

  9. MicroRNA-320 Induces Neurite Outgrowth by Targeting ARPP-1

    PubMed Central

    White, Robin E.; Giffard, Rona G.

    2012-01-01

    MicroRNAs are important in central nervous system development, functioning, and pathophysiology. Here we demonstrate that increasing levels of microRNA 320 (miR-320) for 3 days markedly increases neurite length and at 4 days reduces total cell number in N2A cells. In silico analysis of possible miR-320 targets identified cAMP-regulated phosphoprotein-19 kDa (ARPP-19) and semaphorin 3a (Sema3a) as potential targets that could be involved. ARPP-19 was validated by demonstrating reduced mRNA and protein levels when miR-320 was overexpressed, while miR-320 had no effect on Sema3a expression. ARPP-19 is known to inhibit protein phosphatase-2A (PP2A) activity, which inhibits mitosis and induces neurite outgrowth, making this the likely mechanism. Thus increased levels of miR-320 leads to decreased levels of ARPP-19, increased neurite length, and fewer total cells. These data suggest that miR-320 could play a role in neuronal development and might be a target to enhance neuronal regeneration following injury. PMID:22617447

  10. Neurite formation by neurons derived from adult rat hippocampal progenitor cells is susceptible to myelin inhibition.

    PubMed

    Mellough, Carla B; Cho, Seongeun; Wood, Andrew; Przyborski, Stefan

    2011-09-01

    Myelin-associated inhibitors expressed following injury to the adult central nervous system (CNS) induce growth cone collapse and retraction of the axonal cytoskeleton. Myelin-associated glycoprotein (MAG) is a bi-functional molecule that promotes neuritogenesis in some immature neurons during development then becomes inhibitory to neurite outgrowth as neurons mature. Progress is being made towards the elucidation of the downstream events that regulate myelin inhibition of regeneration in neuronal populations. However it is not known how adult-derived neural stem cells or progenitors respond to myelin during neuronal differentiation and neuritogenesis. Here we examine the effect of MAG on neurons derived from an adult rat hippocampal progenitor cell line (AHPCs). We show that, unlike their developmental counterparts, AHPC-derived neurons are susceptible to MAG inhibition of neuritogenesis during differentiation and display a 57% reduction in neurite outgrowth when compared with controls. We demonstrate that this effect can be overcome (by up to 69%) by activation of the neurotrophin, cyclic AMP and protein kinase A pathways or by Rho-kinase suppression. We also demonstrate that combination of these factors enhanced neurite outgrowth from differentiating neurons in the presence of MAG. This work provides important information for the successful generation of new neurons from adult neural stem cell populations within compromised adult circuitry and is thus directly relevant to endogenous repair and regeneration of the adult CNS. PMID:21256909

  11. Experimental evidence of dynamic re-organization of evolving landscapes under changing climatic forcing

    NASA Astrophysics Data System (ADS)

    Singh, Arvind; Tejedor, Alejandro; Zaliapin, Ilya; Reinhardt, Liam; Foufoula-Georgiou, Efi

    2015-04-01

    The aim of this study is to better understand the dynamic re-organization of an evolving landscape under a scenario of changing climatic forcing for improving our knowledge of geomorphic transport laws under transient conditions and developing predictive models of landscape response to external perturbations. Real landscape observations for long-term analysis are limited and to this end a high resolution controlled laboratory experiment was conducted at the St. Anthony Falls laboratory at the University of Minnesota. Elevation data were collected at temporal resolution of 5 mins and spatial resolution of 0.5 mm as the landscape approached steady state (constant uplift and precipitation rate) and in the transient state (under the same uplift and 5x precipitation). The results reveal rapid topographic re-organization under a five-fold precipitation increase with the fluvial regime expanding into the previously debris dominated regime, accelerated erosion happening at hillslope scales, and rivers shifting from an erosion-limited to a transport-limited regime. From a connectivity and clustering analysis of the erosional and depositional events, we demonstrate the strikingly different spatial patterns of landscape evolution under steady-state (SS) and transient-state (TS), even when the time under SS is "stretched" compared to that under TS such as to match the total volume and PDF of erosional and depositional amounts. We quantify the spatial coupling of hillslopes and channels and demonstrate that hillslopes lead and channels follow in re-organizing the whole landscape under such an amplified precipitation regime.

  12. Importance of considering intraborehole flow in solute transport modeling under highly dynamic flow conditions.

    PubMed

    Ma, Rui; Zheng, Chunmiao; Tonkin, Matt; Zachara, John M

    2011-04-01

    Correct interpretation of tracer test data is critical for understanding transport processes in the subsurface. This task can be greatly complicated by the presence of intraborehole flows in a highly dynamic flow environment. At a new tracer test site (Hanford IFRC) a dynamic flow field created by changes in the stage of the adjacent Columbia River, coupled with a heterogeneous hydraulic conductivity distribution, leads to considerable variations in vertical hydraulic gradients. These variations, in turn, create intraborehole flows in fully-screened (6.5m) observation wells with frequently alternating upward and downward movement. This phenomenon, in conjunction with a highly permeable aquifer formation and small horizontal hydraulic gradients, makes modeling analysis and model calibration a formidable challenge. Groundwater head data alone were insufficient to define the flow model boundary conditions, and the movement of the tracer was highly sensitive to the dynamics of the flow field. This study shows that model calibration can be significantly improved by explicitly considering (a) dynamic flow model boundary conditions and (b) intraborehole flow. The findings from this study underscore the difficulties in interpreting tracer tests and understanding solute transport under highly dynamic flow conditions. PMID:21216023

  13. Total Variation Regularized RPCA for Irregularly Moving Object Detection Under Dynamic Background.

    PubMed

    Cao, Xiaochun; Yang, Liang; Guo, Xiaojie

    2016-04-01

    Moving object detection is one of the most fundamental tasks in computer vision. Many classic and contemporary algorithms work well under the assumption that backgrounds are stationary and movements are continuous, but degrade sharply when they are used in a real detection system, mainly due to: 1) the dynamic background (e.g., swaying trees, water ripples and fountains in real scenarios, as well as raindrops and snowflakes in bad weather) and 2) the irregular object movement (like lingering objects). This paper presents a unified framework for addressing the difficulties mentioned above, especially the one caused by irregular object movement. This framework separates dynamic background from moving objects using the spatial continuity of foreground, and detects lingering objects using the temporal continuity of foreground. The proposed framework assumes that the dynamic background is sparser than the moving foreground that has smooth boundary and trajectory. We regard the observed video as being made up of the sum of a low-rank static background, a sparse and smooth foreground, and a sparser dynamic background. To deal with this decomposition, i.e., a constrained minimization problem, the augmented Lagrangian multiplier method is employed with the help of the alternating direction minimizing strategy. Extensive experiments on both simulated and real data demonstrate that our method significantly outperforms the state-of-the-art approaches, especially for the cases with dynamic backgrounds and discontinuous movements. PMID:25910272

  14. Repeatable Population Dynamics among Vesicular Stomatitis Virus Lineages Evolved under High Co-infection.

    PubMed

    Williams, Elizabeth S C P; Morales, Nadya M; Wasik, Brian R; Brusic, Vesna; Whelan, Sean P J; Turner, Paul E

    2016-01-01

    Parasites and hosts can experience oscillatory cycles, where the densities of these interacting species dynamically fluctuate through time. Viruses with different replication strategies can also interact to produce cyclical dynamics. Frequent cellular co-infection can select for defective-interfering particles (DIPs): "cheater" viruses with shortened genomes that interfere with intracellular replication of full-length (ordinary) viruses. DIPs are positively selected when rare because they out-replicate ordinary viruses during co-infection, but DIPs are negatively selected when common because ordinary viruses become unavailable for intracellular exploitation via cheating. Here, we tested whether oscillatory dynamics of ordinary viruses were similar across independently evolved populations of vesicular stomatitis virus (VSV). Results showed identical cyclical dynamics across populations in the first 10 experimental passages, which transitioned to repeatable dampened oscillations by passage 20. Genomic analyses revealed parallel molecular substitutions across populations, particularly novel mutations that became dominant by passage 10. Our study showed that oscillatory dynamics and molecular evolution of interacting viruses were highly repeatable in VSV populations passaged under frequent co-infection. Furthermore, our data suggested that frequent co-infection with DIPs caused lowered performance of full-length viruses, by reducing their population densities by orders of magnitude compared to reproduction of ordinary viruses during strictly clonal infections. PMID:27065953

  15. Repeatable Population Dynamics among Vesicular Stomatitis Virus Lineages Evolved under High Co-infection

    PubMed Central

    Williams, Elizabeth S. C. P.; Morales, Nadya M.; Wasik, Brian R.; Brusic, Vesna; Whelan, Sean P. J.; Turner, Paul E.

    2016-01-01

    Parasites and hosts can experience oscillatory cycles, where the densities of these interacting species dynamically fluctuate through time. Viruses with different replication strategies can also interact to produce cyclical dynamics. Frequent cellular co-infection can select for defective-interfering particles (DIPs): “cheater” viruses with shortened genomes that interfere with intracellular replication of full-length (ordinary) viruses. DIPs are positively selected when rare because they out-replicate ordinary viruses during co-infection, but DIPs are negatively selected when common because ordinary viruses become unavailable for intracellular exploitation via cheating. Here, we tested whether oscillatory dynamics of ordinary viruses were similar across independently evolved populations of vesicular stomatitis virus (VSV). Results showed identical cyclical dynamics across populations in the first 10 experimental passages, which transitioned to repeatable dampened oscillations by passage 20. Genomic analyses revealed parallel molecular substitutions across populations, particularly novel mutations that became dominant by passage 10. Our study showed that oscillatory dynamics and molecular evolution of interacting viruses were highly repeatable in VSV populations passaged under frequent co-infection. Furthermore, our data suggested that frequent co-infection with DIPs caused lowered performance of full-length viruses, by reducing their population densities by orders of magnitude compared to reproduction of ordinary viruses during strictly clonal infections. PMID:27065953

  16. Dynamic Stability Optimization of Laminated Composite Plates under Combined Boundary Loading

    NASA Astrophysics Data System (ADS)

    Shafei, Erfan; Kabir, Mohammad Zaman

    2011-12-01

    Dynamic stability and design optimization of laminated simply supported plates under planar conservative boundary loads are investigated in current study. Examples can be found in internal connecting elements of spacecraft and aerospace structures subjected to edge axial and shear loads. Designation of such elements is function of layup configuration, plate aspect ratio, loading combinations, and layup thickness. An optimum design aims maximum stability load satisfying a predefined stable vibration frequency. The interaction between compound loading and layup angle parameter affects the order of merging vibration modes and may stabilize the dynamic response. Laminated plates are assumed to be angle-plies symmetric to mid-plane surface. Dynamic equilibrium PDE has been solved using kernel integral transformation for modal frequency values and eigenvalue-based orthogonal functions for critical stability loads. The dictating dynamic stability mode is shown to be controlled by geometric stiffness distributions of composite plates. Solution of presented design optimization problem has been done using analytical approach combined with interior penalty multiplier algorithm. The results are verified by FEA approach and stability zones of original and optimized plates are stated as final data. Presented method can help designers to stabilize the dynamic response of composite plates by selecting an optimized layup orientation and thickness for prescribed design circumstances.

  17. Experimental Characterization of the Anatomical Structures of the Lumbar Spine Under Dynamic Sagittal Bending.

    PubMed

    Bradfield, C A; Demetropoulos, C K; Luongo, M E; Pyles, C O; Armiger, R S; Merkle, A C

    2015-01-01

    Underbody blast (UBB) events transmit high-rate vertical loads through the seated occupant’s lumbar spine and have a high probability of inducing severe injury. While previous studies have characterized the lumbar spine under quasi-static loading, additional work should focus on the complex kinetic and kinematic response under high loading rates. To discern the biomechanical influence of the lumbar spine’s anatomical structures during dynamic loading, the axial force, flexion-extension moments and range of motion for lumbar motion segments (n=18) were measured during different states of progressive dissection. Pre-compression was applied using a static mass while dynamic bending was applied using an offset drop mass. Dynamic loading resulted in peak axial loads of 4,224±133 N, while maximum peak extension and flexion moments were 19.6±12.5 and -44.8±8.6 Nm in the pre-dissected state, respectively. Upon dissection, transection of the interspinous ligament, ligamentum flavum and facet capsules resulted in significantly larger flexion angles, while the removal of the posterior elements increased the total peak angular displacement in extension from 3.3±1.5 to 5.0±1.7 degrees (p=0.002). This study provides insight on the contribution of individual anatomical components on overall lumbar response under high-rate loading, as well as validation data for numerical models. PMID:25996712

  18. Impaired Neurite Contact Guidance in Ubiquitin Ligase E3a (Ube3a)-Deficient Hippocampal Neurons on Nanostructured Substrates.

    PubMed

    Tonazzini, I; Meucci, S; Van Woerden, G M; Elgersma, Y; Cecchini, M

    2016-04-01

    Recent discoveries indicate that during neuronal development the signaling processes that regulate extracellular sensing (e.g., adhesion, cytoskeletal dynamics) are important targets for ubiquitination-dependent regulation, in particular through E3 ubiquitin ligases. Among these, Ubiquitin E3a ligase (UBE3A) has a key role in brain functioning, but its function and how its deficiency results in the neurodevelopmental disorder Angelman syndrome is still unclear. Here, the role of UBE3A is investigated in neurite contact guidance during neuronal development, in vitro. The microtopography sensing of wild-type and Ube3a-deficient hippocampal neurons is studied by exploiting gratings with different topographical characteristics, with the aim to compare their capabilities to read and follow physical directional stimuli. It is shown that neuronal contact guidance is defective in Ube3a-deficient neurons, and this behavior is linked to an impaired activation of the focal adhesion signaling pathway. Taken together, the results suggest that the neuronal contact sensing machinery might be affected in Angelman syndrome. PMID:26845073

  19. Modeling dynamic stall on wind turbine blades under rotationally augmented flow fields

    SciTech Connect

    Guntur, S.; Schreck, S.; Sorensen, N. N.; Bergami, L.

    2015-04-22

    It is well known that airfoils under unsteady flow conditions with a periodically varying angle of attack exhibit aerodynamic characteristics different from those under steady flow conditions, a phenomenon commonly known as dynamic stall. It is also well known that the steady aerodynamic characteristics of airfoils in the inboard region of a rotating blade differ from those under steady two-dimensional (2D) flow conditions, a phenomenon commonly known as rotational augmentation. This paper presents an investigation of these two phenomena together in the inboard parts of wind turbine blades. This analysis is carried out using data from three sources: (1) the National Renewable Energy Laboratory’s Unsteady Aerodynamics Experiment Phase VI experimental data, including constant as well as continuously pitching blade conditions during axial operation, (2) data from unsteady Delayed Detached Eddy Simulations (DDES) carried out using the Technical University of Denmark’s in-house flow solver Ellipsys3D, and (3) data from a simplified model based on the blade element momentum method with a dynamic stall subroutine that uses rotationally augmented steady-state polars obtained from steady Phase VI experimental sequences, instead of the traditional 2D nonrotating data. The aim of this work is twofold. First, the blade loads estimated by the DDES simulations are compared to three select cases of the N sequence experimental data, which serves as a validation of the DDES method. Results show reasonable agreement between the two data in two out of three cases studied. Second, the dynamic time series of the lift and the moment polars obtained from the experiments are compared to those from the dynamic stall subroutine that uses the rotationally augmented steady polars. This allowed the differences between the stall phenomenon on the inboard parts of harmonically pitching blades on a rotating wind turbine and the classic dynamic stall representation in 2D flow to be

  20. Formation and phase transitions of methane hydrates under dynamic loadings: Compression rate dependent kinetics

    NASA Astrophysics Data System (ADS)

    Chen, Jing-Yin; Yoo, Choong-Shik

    2012-03-01

    We describe high-pressure kinetic studies of the formation and phase transitions of methane hydrates (MH) under dynamic loading conditions, using a dynamic-diamond anvil cell (d-DAC) coupled with time-resolved confocal micro-Raman spectroscopy and high-speed microphotography. The time-resolved spectra and dynamic pressure responses exhibit profound compression-rate dependences associated with both the formation and the solid-solid phase transitions of MH-I to II and MH-II to III. Under dynamic loading conditions, MH forms only from super-compressed water and liquid methane in a narrow pressure range between 0.9 and 1.6 GPa at the one-dimensional (1D) growth rate of 42 μm/s. MH-I to II phase transition occurs at the onset of water solidification 0.9 GPa, following a diffusion controlled mechanism. We estimated the activation volume to be -109 ± 29 Å3, primarily associated with relatively slow methane diffusion which follows the rapid interfacial reconstruction, or martensitic displacements of atomic positions and hydrogen bonds, of 51262 water cages in MH-I to 4351263 cages in MH-II. MH-II to III transition, on the other hand, occurs over a broad pressure range between 1.5 and 2.2 GPa, following a reconstructive mechanism from super-compressed MH-II clathrates to a broken ice-filled viscoelastic solid of MH-III. It is found that the profound dynamic effects observed in the MH formation and phase transitions are primarily governed by the stability of water and ice phases at the relevant pressures.

  1. Formation and phase transitions of methane hydrates under dynamic loadings: compression rate dependent kinetics.

    PubMed

    Chen, Jing-Yin; Yoo, Choong-Shik

    2012-03-21

    We describe high-pressure kinetic studies of the formation and phase transitions of methane hydrates (MH) under dynamic loading conditions, using a dynamic-diamond anvil cell (d-DAC) coupled with time-resolved confocal micro-Raman spectroscopy and high-speed microphotography. The time-resolved spectra and dynamic pressure responses exhibit profound compression-rate dependences associated with both the formation and the solid-solid phase transitions of MH-I to II and MH-II to III. Under dynamic loading conditions, MH forms only from super-compressed water and liquid methane in a narrow pressure range between 0.9 and 1.6 GPa at the one-dimensional (1D) growth rate of 42 μm/s. MH-I to II phase transition occurs at the onset of water solidification 0.9 GPa, following a diffusion controlled mechanism. We estimated the activation volume to be -109±29 Å(3), primarily associated with relatively slow methane diffusion which follows the rapid interfacial reconstruction, or martensitic displacements of atomic positions and hydrogen bonds, of 5(12)6(2) water cages in MH-I to 4(3)5(12)6(3) cages in MH-II. MH-II to III transition, on the other hand, occurs over a broad pressure range between 1.5 and 2.2 GPa, following a reconstructive mechanism from super-compressed MH-II clathrates to a broken ice-filled viscoelastic solid of MH-III. It is found that the profound dynamic effects observed in the MH formation and phase transitions are primarily governed by the stability of water and ice phases at the relevant pressures. PMID:22443783

  2. Uncertainty in predicting range dynamics of endemic alpine plants under climate warming.

    PubMed

    Hülber, Karl; Wessely, Johannes; Gattringer, Andreas; Moser, Dietmar; Kuttner, Michael; Essl, Franz; Leitner, Michael; Winkler, Manuela; Ertl, Siegrun; Willner, Wolfgang; Kleinbauer, Ingrid; Sauberer, Norbert; Mang, Thomas; Zimmermann, Niklaus E; Dullinger, Stefan

    2016-07-01

    Correlative species distribution models have long been the predominant approach to predict species' range responses to climate change. Recently, the use of dynamic models is increasingly advocated for because these models better represent the main processes involved in range shifts and also simulate transient dynamics. A well-known problem with the application of these models is the lack of data for estimating necessary parameters of demographic and dispersal processes. However, what has been hardly considered so far is the fact that simulating transient dynamics potentially implies additional uncertainty arising from our ignorance of short-term climate variability in future climatic trends. Here, we use endemic mountain plants of Austria as a case study to assess how the integration of decadal variability in future climate affects outcomes of dynamic range models as compared to projected long-term trends and uncertainty in demographic and dispersal parameters. We do so by contrasting simulations of a so-called hybrid model run under fluctuating climatic conditions with those based on a linear interpolation of climatic conditions between current values and those predicted for the end of the 21st century. We find that accounting for short-term climate variability modifies model results nearly as differences in projected long-term trends and much more than uncertainty in demographic/dispersal parameters. In particular, range loss and extinction rates are much higher when simulations are run under fluctuating conditions. These results highlight the importance of considering the appropriate temporal resolution when parameterizing and applying range-dynamic models, and hybrid models in particular. In case of our endemic mountain plants, we hypothesize that smoothed linear time series deliver more reliable results because these long-lived species are primarily responsive to long-term climate averages. PMID:27061825

  3. Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons

    PubMed Central

    Sinisi, M; Fox, M; MacQuillan, A; Quick, T; Korchev, Y; Bountra, C; McCarthy, T; Anand, P

    2016-01-01

    Background Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, β tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone. Results Morphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and β tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401. Conclusion Mycolactone

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

    PubMed Central

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

    2014-01-01

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

  5. A Novel Approach for Dynamic Testing of Total Hip Dislocation under Physiological Conditions

    PubMed Central

    Herrmann, Sven; Kluess, Daniel; Kaehler, Michael; Grawe, Robert; Rachholz, Roman; Souffrant, Robert; Zierath, János; Bader, Rainer; Woernle, Christoph

    2015-01-01

    Constant high rates of dislocation-related complications of total hip replacements (THRs) show that contributing factors like implant position and design, soft tissue condition and dynamics of physiological motions have not yet been fully understood. As in vivo measurements of excessive motions are not possible due to ethical objections, a comprehensive approach is proposed which is capable of testing THR stability under dynamic, reproducible and physiological conditions. The approach is based on a hardware-in-the-loop (HiL) simulation where a robotic physical setup interacts with a computational musculoskeletal model based on inverse dynamics. A major objective of this work was the validation of the HiL test system against in vivo data derived from patients with instrumented THRs. Moreover, the impact of certain test conditions, such as joint lubrication, implant position, load level in terms of body mass and removal of muscle structures, was evaluated within several HiL simulations. The outcomes for a normal sitting down and standing up maneuver revealed good agreement in trend and magnitude compared with in vivo measured hip joint forces. For a deep maneuver with femoral adduction, lubrication was shown to cause less friction torques than under dry conditions. Similarly, it could be demonstrated that less cup anteversion and inclination lead to earlier impingement in flexion motion including pelvic tilt for selected combinations of cup and stem positions. Reducing body mass did not influence impingement-free range of motion and dislocation behavior; however, higher resisting torques were observed under higher loads. Muscle removal emulating a posterior surgical approach indicated alterations in THR loading and the instability process in contrast to a reference case with intact musculature. Based on the presented data, it can be concluded that the HiL test system is able to reproduce comparable joint dynamics as present in THR patients. PMID:26717236

  6. A Novel Approach for Dynamic Testing of Total Hip Dislocation under Physiological Conditions.

    PubMed

    Herrmann, Sven; Kluess, Daniel; Kaehler, Michael; Grawe, Robert; Rachholz, Roman; Souffrant, Robert; Zierath, János; Bader, Rainer; Woernle, Christoph

    2015-01-01

    Constant high rates of dislocation-related complications of total hip replacements (THRs) show that contributing factors like implant position and design, soft tissue condition and dynamics of physiological motions have not yet been fully understood. As in vivo measurements of excessive motions are not possible due to ethical objections, a comprehensive approach is proposed which is capable of testing THR stability under dynamic, reproducible and physiological conditions. The approach is based on a hardware-in-the-loop (HiL) simulation where a robotic physical setup interacts with a computational musculoskeletal model based on inverse dynamics. A major objective of this work was the validation of the HiL test system against in vivo data derived from patients with instrumented THRs. Moreover, the impact of certain test conditions, such as joint lubrication, implant position, load level in terms of body mass and removal of muscle structures, was evaluated within several HiL simulations. The outcomes for a normal sitting down and standing up maneuver revealed good agreement in trend and magnitude compared with in vivo measured hip joint forces. For a deep maneuver with femoral adduction, lubrication was shown to cause less friction torques than under dry conditions. Similarly, it could be demonstrated that less cup anteversion and inclination lead to earlier impingement in flexion motion including pelvic tilt for selected combinations of cup and stem positions. Reducing body mass did not influence impingement-free range of motion and dislocation behavior; however, higher resisting torques were observed under higher loads. Muscle removal emulating a posterior surgical approach indicated alterations in THR loading and the instability process in contrast to a reference case with intact musculature. Based on the presented data, it can be concluded that the HiL test system is able to reproduce comparable joint dynamics as present in THR patients. PMID:26717236

  7. Age effects on the control of dynamic balance during step adjustments under temporal constraints.

    PubMed

    Nakano, Wataru; Fukaya, Takashi; Kobayashi, Satomi; Ohashi, Yukari

    2016-06-01

    This study investigated the age effects on the control of dynamic balance during step adjustments under temporal constraints. Fifteen young adults and 14 older adults avoided a virtual white planar obstacle by lengthening or shortening their steps under free or constrained conditions. In the anterior-posterior direction, older adults demonstrated significantly decreased center of mass velocity at the swing foot contact under temporal constraints. Additionally, the distances between the 'extrapolated center of mass' position and base of support at the swing foot contact were greater in older adults than young adults. In the mediolateral direction, center of mass displacement was significantly increased in older adults compared with young adults. Consequently, older adults showed a significantly increased step width at the swing foot contact in the constraint condition. Overall, these data suggest that older adults demonstrate a conservative strategy to maintain anterior-posterior stability. By contrast, although older adults are able to modulate their step width to maintain mediolateral dynamic balance, age-related changes in mediolateral balance control under temporal constraints may increase the risk of falls in the lateral direction during obstacle negotiation. PMID:26852293

  8. TRBUCKL - A NASTRAN DMAP ALTER FOR LINEAR BUCKLING ANALYSIS UNDER DYNAMIC LOADING

    NASA Technical Reports Server (NTRS)

    Aiello, R. A.

    1994-01-01

    Delaminations near the outer surface of a laminate are susceptible to local buckling and buckling-induced delamination propagation when the laminate is subjected to transverse impact loading. This results in a loss of stiffness and strength. TRBUCKL is an unique dynamic delamination buckling and delamination propagation analysis capability that can be incorporated into the structural analysis program, NASTRAN. This capability will aid engineers in the design of structures incorporating composite laminates. The capability consists of: (1) a modification of the direct time integration solution sequence which provides a new analysis algorithm that can be used to predict delamination buckling in a laminate subjected to dynamic loading; and (2) a new method of modeling the composite laminate using plate bending elements and multipoint constraints. The capability now exists to predict the time at which the onset of dynamic delamination buckling occurs, the dynamic buckling mode shape, and the dynamic delamination strain energy release rate. A procedure file for NASTRAN, TRBUCKL predicts both impact induced buckling in composite laminates with initial delaminations and the strain energy release rate due to extension of the delamination. In addition, the file is useful in calculating the dynamic delamination strain energy release rate for a composite laminate under impact loading. This procedure simplifies the simulation of progressive crack extension. TRBUCKL has been incorporated into COSMIC NASTRAN. TRBUCKL is a DMAP Alter for NASTRAN. It is intended for use only with the COSMIC NASTRAN Direct Transient Analysis (RF 9) solution sequence. The program is available as a listing only. TRBUCKL was developed in 1987.

  9. Dynamic and failure properties of high damping rubber bearing under high axial stress

    SciTech Connect

    Ishizuka, Hidetake; Murota, Nobuo; Fukumori, Takeshi

    1995-12-01

    Seismic isolation bearings have been used under axial stresses less than 100(kgf/cm{sup 2}) for many years. If higher axial loads can be applied, however, a larger period shift will be achieved and the size of the isolation devices may be reduced resulting in a cost reduction of the bearing. This paper describes experimental studies of dynamic and failure properties of high damping rubber bearings (HDR) under high axial stress of over 120(kgf/cm{sup 2}) compared with the conventional stress of 65(kgf/cm{sup 2}). The results show that HDR continues to have stable performance under high axial stress with high shear strain. It indicates that high axial stress over 100(kgf/cm{sup 2}) is within the capability of the BDR isolation bearing.

  10. Electrical response of carbon nanotube reinforced nanocomposites under static and dynamic loading

    NASA Astrophysics Data System (ADS)

    Heeder, Nicholas J.

    The electrical response of multi-wall carbon nanotube (MWCNT) reinforced epoxy nanocomposites under quasi-static and dynamic compressive loading is experimentally investigated. The objective of this project was to study the electrical response of CNT-reinforced nanocomposites under mechanical loading where the carbon nanotubes are used to create an internal sensory network within, capable of detecting important information such as strain and damage. Experimental techniques were developed to effectively obtain the bulk resistance change of the nanocomposite material while subjected to quasi-static and dynamic loading. A combination of shear mixing and ultrasonication was used to fabricate the low resistance nanocomposite material. The fabrication process parameters and the optimum weight fraction of MWCNTs for generating a well-dispersed percolation network were first determined. A screw-driven testing machine, a drop weight tower, and a split Hopkinson pressure bar (SHPB) apparatus were utilized to load the specimens. Absolute resistance values were measured with a high-resolution four-point probe method for both quasi-static and dynamic loading. In addition to measuring the percentage change in electrical resistance, real-time damage was captured using high-speed photography. The real-time damage was correlated to both load and percentage change in resistance profiles to better understand the electrical behavior of CNT reinforced nanocomposites under mechanical loading. The experimental findings indicate that the bulk electrical resistance of the nanocomposites, under both quasi-static and drop weight loading conditions, initially decreased between 40%--60% during compression and then increased as damage initiated and propagated. Similarly, a 65%--85% decrease in resistance was observed when the nanocomposites were subjected to SHPB loading. Damage initiation and propagation was also captured by the resistance measurements owing to the ability of the CNTs to be

  11. Communication: Dynamical and structural analyses of solid hydrogen under vapor pressure

    SciTech Connect

    Hyeon-Deuk, Kim; Ando, Koji

    2015-11-07

    Nuclear quantum effects play a dominant role in determining the phase diagram of H{sub 2}. With a recently developed quantum molecular dynamics simulation method, we examine dynamical and structural characters of solid H{sub 2} under vapor pressure, demonstrating the difference from liquid and high-pressure solid H{sub 2}. While stable hexagonal close-packed lattice structures are reproduced with reasonable lattice phonon frequencies, the most stable adjacent configuration exhibits a zigzag structure, in contrast with the T-shape liquid configuration. The periodic angular distributions of H{sub 2} molecules indicate that molecules are not a completely free rotor in the vapor-pressure solid reflecting asymmetric potentials from surrounding molecules on adjacent lattice sites. Discrete jumps of librational and H–H vibrational frequencies as well as H–H bond length caused by structural rearrangements under vapor pressure effectively discriminate the liquid and solid phases. The obtained dynamical and structural information of the vapor-pressure H{sub 2} solid will be useful in monitoring thermodynamic states of condensed hydrogens.

  12. Adhesion dynamics of circulating tumor cells under shear flow in a bio-functionalized microchannel

    NASA Astrophysics Data System (ADS)

    Siu-Lun Cheung, Luthur; Zheng, Xiangjun; Wang, Lian; Baygents, James C.; Guzman, Roberto; Schroeder, Joyce A.; Heimark, Ronald L.; Zohar, Yitshak

    2011-05-01

    The adhesion dynamics of circulating tumor cells in a bio-functionalized microchannel under hydrodynamic loading is explored experimentally and analyzed theoretically. EpCAM antibodies are immobilized on the microchannel surface to specifically capture EpCAM-expressing target breast cancer cells MDA-MB-231 from a homogeneous cell suspension in shear flow. In the cross-stream direction, gravity is the dominant physical mechanism resulting in continuous interaction between the EpCAM cell receptors and the immobilized surface anti-EpCAM ligands. Depending on the applied shear rate, three dynamic states have been characterized: firm adhesion, rolling adhesion and free rolling. The steady-state velocity under adhesion- and free-rolling conditions as well as the time-dependent velocity in firm adhesion has been characterized experimentally, based on video recordings of target cell motion in functionalized microchannels. A previously reported theoretical model, utilizing a linear spring to represent the specific receptor-ligand bonds, has been adopted to analyze adhesion dynamics including features such as the cell-surface binding force and separation gap. By fitting theoretical predictions to experimental measurements, a unified exponential decay function is proposed to describe the target cell velocity evolution during capture; the fitting parameters, velocity and time scales, depend on the particular cell-surface system.

  13. Effect of random microstructure on crack propagation in cortical bone tissue under dynamic loading

    NASA Astrophysics Data System (ADS)

    Gao, X.; Li, S.; Adel-Wahab, A.; Silberschmidt, V.

    2013-07-01

    A fracture process in a cortical bone tissue depends on various factors, such as bone loss, heterogeneous microstructure, variation of its material properties and accumulation of microcracks. Therefore, it is crucial to comprehend and describe the effect of microstructure and material properties of the components of cortical bone on crack propagation in a dynamic loading regime. At the microscale level, osteonal bone demonstrates a random distribution of osteons imbedded in an interstitial matrix and surrounded by a thin layer known as cement line. Such a distribution of osteons can lead to localization of deformation processes. The global mechanical behavior of bone and the crack-propagation process are affected by such localization under external loads. Hence, the random distribution of microstructural features plays a key role in the fracture process of cortical bone. The purpose of this study is two-fold: firstly, to develop two-dimensional microstructured numerical models of cortical bone tissue in order to examine the interaction between the propagating crack and bone microstructure using an extended finite-element method under both quasi-static and dynamic loading conditions; secondly, to investigate the effect of randomly distributed microstructural constituents on the crack propagation processes and crack paths. The obtained results of numerical simulations showed the influence of random microstructure on the global response of bone tissue at macroscale and on the crack-propagation process for quasi-static and dynamic loading conditions.

  14. Communication: Dynamical and structural analyses of solid hydrogen under vapor pressure

    NASA Astrophysics Data System (ADS)

    Hyeon-Deuk, Kim; Ando, Koji

    2015-11-01

    Nuclear quantum effects play a dominant role in determining the phase diagram of H2. With a recently developed quantum molecular dynamics simulation method, we examine dynamical and structural characters of solid H2 under vapor pressure, demonstrating the difference from liquid and high-pressure solid H2. While stable hexagonal close-packed lattice structures are reproduced with reasonable lattice phonon frequencies, the most stable adjacent configuration exhibits a zigzag structure, in contrast with the T-shape liquid configuration. The periodic angular distributions of H2 molecules indicate that molecules are not a completely free rotor in the vapor-pressure solid reflecting asymmetric potentials from surrounding molecules on adjacent lattice sites. Discrete jumps of librational and H-H vibrational frequencies as well as H-H bond length caused by structural rearrangements under vapor pressure effectively discriminate the liquid and solid phases. The obtained dynamical and structural information of the vapor-pressure H2 solid will be useful in monitoring thermodynamic states of condensed hydrogens.

  15. Nonlinear dynamics of initially imperfect functionally graded circular cylindrical shell under complex loads

    NASA Astrophysics Data System (ADS)

    Liu, Y. Z.; Hao, Y. X.; Zhang, W.; Chen, J.; Li, S. B.

    2015-07-01

    The nonlinear vibration of a simply supported FGM cylindrical shell with small initial geometric imperfection under complex loads is studied. The effects of radial harmonic excitation, compressive in-plane force combined with supersonic aerodynamic and thermal loads are considered. The small initial geometric imperfection of the cylindrical shell is characterized in the form of the sine-type trigonometric functions. The effective material properties of this FGM cylindrical shell are graded in the radial direction according to a simple power law in terms of the volume fractions. Based on Reddy's third-order shear deformation theory, von Karman-type nonlinear kinematics and Hamilton's principle, the nonlinear partial differential equation that controls the shell dynamics is derived. Both axial symmetric and driven modes of the cylindrical shell deflection pattern are included. Furthermore, the equations of motion can be reduced into a set of coupled nonlinear ordinary differential equations by applying Galerkin's method. In the study of the nonlinear dynamics responses of small initial geometric imperfect FGM cylindrical shell under complex loads, the 4th order Runge-Kutta method is used to obtain time history, phase portraits, bifurcation diagrams and Poincare maps with different parameters. The effects of external loads, geometric imperfections and volume fractions on the nonlinear dynamics of the system are discussed.

  16. Mechanisms of compensatory dynamics in zooplankton and maintenance of food chain efficiency under toxicant stress.

    PubMed

    Mano, Hiroyuki; Tanaka, Yoshinari

    2016-03-01

    Communities with species that are tolerant to environmental stresses may be able to maintain the ecosystem functions under the stress, because the tolerant species can compensate for the loss of sensitive species. In this study, we focused on the food chain efficiency (FCE), the trophic transfer across three trophic levels, as an important process for ecosystem function, and examined the conditions under which such compensation could occur with aquarium experiments using an insecticide (methomyl) as the stressor. Our aquariums included one of two pairs of insecticide-tolerant and insecticide-sensitive cladoceran species, and a fish as the predator. The response of FCE to the insecticide stress, as indicated by the fish biomass production, depended on the zooplankton species combinations. FCE and total zooplankton biomass were maintained in the pair in which the compensatory changes of species abundances were clear, whereas they decreased in the pair in which the compensatory changes were not clear. This indicated the compensatory dynamics in the zooplankton community responsible for the observed resistance to the stress. We inferred the driving factors for the compensatory dynamics and the community resistance with respect to species traits of ecological importance, and concluded that a dissimilarity between species as regards the tolerance trait and a clear trade-off between the tolerance and the competitive ability was required to drive the compensatory dynamics, and a similarity or a superiority of the tolerant species as regards the functional effect trait (the predator avoidance and the reproductive potential) were required to maintain FCE. PMID:26683817

  17. Under-the-barrier dynamics in laser-induced relativistic tunneling.

    PubMed

    Klaiber, Michael; Yakaboylu, Enderalp; Bauke, Heiko; Hatsagortsyan, Karen Z; Keitel, Christoph H

    2013-04-12

    The tunneling dynamics in relativistic strong-field ionization is investigated with the aim to develop an intuitive picture for the relativistic tunneling regime. We demonstrate that the tunneling picture applies also in the relativistic regime by introducing position dependent energy levels. The quantum dynamics in the classically forbidden region features two time scales, the typical time that characterizes the probability density's decay of the ionizing electron under the barrier (Keldysh time) and the time interval which the electron spends inside the barrier (Eisenbud-Wigner-Smith tunneling time). In the relativistic regime, an electron momentum shift as well as a spatial shift along the laser propagation direction arise during the under-the-barrier motion which are caused by the laser magnetic field induced Lorentz force. The momentum shift is proportional to the Keldysh time, while the wave-packet's spatial drift is proportional to the Eisenbud-Wigner-Smith time. The signature of the momentum shift is shown to be present in the ionization spectrum at the detector and, therefore, observable experimentally. In contrast, the signature of the Eisenbud-Wigner-Smith time delay disappears at far distances for pure quasistatic tunneling dynamics. PMID:25167261

  18. Communication: Dynamical and structural analyses of solid hydrogen under vapor pressure.

    PubMed

    Hyeon-Deuk, Kim; Ando, Koji

    2015-11-01

    Nuclear quantum effects play a dominant role in determining the phase diagram of H2. With a recently developed quantum molecular dynamics simulation method, we examine dynamical and structural characters of solid H2 under vapor pressure, demonstrating the difference from liquid and high-pressure solid H2. While stable hexagonal close-packed lattice structures are reproduced with reasonable lattice phonon frequencies, the most stable adjacent configuration exhibits a zigzag structure, in contrast with the T-shape liquid configuration. The periodic angular distributions of H2 molecules indicate that molecules are not a completely free rotor in the vapor-pressure solid reflecting asymmetric potentials from surrounding molecules on adjacent lattice sites. Discrete jumps of librational and H-H vibrational frequencies as well as H-H bond length caused by structural rearrangements under vapor pressure effectively discriminate the liquid and solid phases. The obtained dynamical and structural information of the vapor-pressure H2 solid will be useful in monitoring thermodynamic states of condensed hydrogens. PMID:26547150

  19. Dynamic analysis of parametrically excited system under uncertainties and multi-frequency excitations

    NASA Astrophysics Data System (ADS)

    Wei, Sha; Han, Qinkai; Peng, Zhike; Chu, Fulei

    2016-05-01

    Some system parameters in mechanical systems are always uncertain due to uncertainties in geometric and material properties, lubrication condition and wear. For a more reasonable estimation of dynamic analysis of the parametrically excited system, the effect of uncertain parameters should be taken into account. This paper presents a new non-probabilistic analysis method for solving the dynamic responses of parametrically excited systems under uncertainties and multi-frequency excitations. By using the multi-dimensional harmonic balance method (MHBM) and the Chebyshev inclusion function (CIF), an interval multi-dimensional harmonic balance method (IMHBM) is obtained. To illustrate the accuracy of the proposed method, a time-varying geared system of wind turbine with different kinds of uncertainties is demonstrated. By comparing with the results of the scanning method, it is shown that the presented method is valid and effective for the parametrically excited system with uncertainties and multi-frequency excitations. The effects of some uncertain system parameters including uncertain mesh stiffnesses and uncertain bearing stiffnesses on the frequency responses of the system are also discussed in detail. It is shown that the dynamic responses of the system are insensitive to the uncertain mesh stiffness and bearing stiffnesses of the planetary gear stage. The uncertain bearing stiffnesses of the intermediate and high-speed stages will lead to relatively large uncertainties in the dynamic responses around resonant regions. It will provide valuable guidance for the optimal design and condition monitoring of wind turbine gearboxes.

  20. Translocation dynamics of knotted polymers under a constant or periodic external field.

    PubMed

    Narsimhan, Vivek; Renner, C Benjamin; Doyle, Patrick S

    2016-06-14

    We perform Brownian dynamics simulations to examine how knots alter the dynamics of polymers moving through nanopores under an external field. In the first part of this paper, we study the situation when the field is constant. Here, knots halt translocation above a critical force with jamming occurring at smaller forces for twist topologies compared to non-twist topologies. Slightly below the jamming transition, the polymer's transit times exhibit large fluctuations. This phenomenon is an example of the knot's molecular individualism since the conformation of the knot plays a large role in the chain's subsequent dynamics. In the second part of the paper, we study the motion of the chain when one cycles the field on and off. If the off time is comparable to the knot's relaxation time, one can adjust the swelling of the knot at the pore and hence design strategies to ratchet the polymer in a controllable fashion. We examine how the off time affects the ratcheting dynamics. We also examine how this strategy alters the fluctuations in the polymer's transit time. We find that cycling the force field can reduce fluctuations near the knot's jamming transition, but can enhance the fluctuations at very high forces since knots get trapped in metastable states during the relaxation process. The latter effect appears to be more prominent for non-torus topologies than torus ones. We conclude by discussing the feasibility of this approach to control polymer motion in biotechnology applications such as sequencing. PMID:27181288

  1. Dynamic spectral characteristics measurement of DFB interband cascade laser under injection current tuning

    NASA Astrophysics Data System (ADS)

    Du, Zhenhui; Luo, Gang; An, Ying; Li, Jinyi

    2016-07-01

    The dynamic spectral properties of semiconductor lasers during its tuning are very important for frequency modulation-based applications. The spectral properties of a distributed feedback (DFB) interband cascade laser (ICL) under injection current tuning (i.e., slope efficiency, dynamic tuning rate, and instantaneous linewidth) were measured by using short delayed self-heterodyne interferometry combined with time-frequency analysis of the interferometric signal. The relations of these spectral characteristics with the injection current, tuning frequency, and operating temperature of the laser were investigated as well. The dynamic tuning rate of the laser varies from 0.07 nm/mA to 0.16 nm/mA depending on the injection current and tuning frequency, which is considerably below the static tuning rate 0.20 nm/mA. The laser instantaneous linewidth increases within 360 kHz to 760 kHz as the injection current increases or the tuning frequency increases. Unexpectedly, both the dynamic tuning rate and linewidth seem not to be related to the operating temperature of the laser. These results will be very useful for understanding the spectral properties and optimizing the frequency modulation of DFB-ICLs.

  2. Quench dynamics of a Bose-Einstein condensate under synthetic spin-orbit coupling

    NASA Astrophysics Data System (ADS)

    Deng, Tian-Shu; Zhang, Wei; Yi, Wei; Guo, Guang-Can

    2016-05-01

    We study the quench dynamics of a Bose-Einstein condensate under a Raman-assisted synthetic spin-orbit coupling. To model the dynamical process, we adopt a self-consistent Bogoliubov approach, which is equivalent to applying the time-dependent Bogoliubov-de Gennes equations. We investigate the dynamics of the condensate fraction as well as the momentum distribution of the Bose gas following a sudden change of system parameters. Typically, the system evolves into a steady state in the long-time limit, which features an oscillating momentum distribution and a stationary condensate fraction. We investigate how different quench parameters such as the inter- and intraspecies interactions and the spin-orbit-coupling parameters affect the condensate fraction in the steady state. Furthermore, we find that the time average of the oscillatory momentum distribution in the long-time limit can be described by a generalized Gibbs ensemble with two branches of momentum-dependent Gibbs temperatures. Our study is relevant to the experimental investigation of dynamical processes in a spin-orbit-coupled Bose-Einstein condensate.

  3. Identification of a Peripheral Nerve Neurite Growth-Promoting Activity by Development and Use of an in vitro Bioassay

    NASA Astrophysics Data System (ADS)

    Sandrock, Alfred W.; Matthew, William D.

    1987-10-01

    The effective regeneration of severed neuronal axons in the peripheral nerves of adult mammals may be explained by the presence of molecules in situ that promote the effective elongation of neurites. The absence of such molecules in the central nervous system of these animals may underlie the relative inability of axons to regenerate in this tissue after injury. In an effort to identify neurite growth-promoting molecules in tissues that support effective axonal regeneration, we have developed an in vitro bioassay that is sensitive to substrate-bound factors of peripheral nerve that influence the growth of neurites. In this assay, neonatal rat superior cervical ganglion explants are placed on longitudinal cryostat sections of fresh-frozen sciatic nerve, and the regrowing axons are visualized by catecholamine histofluorescence. Axons are found to regenerate effectively over sciatic nerve tissue sections. When ganglia are similarly explanted onto cryostat sections of adult rat central nervous system tissue, however, axonal regeneration is virtually absent. We have begun to identify the molecules in peripheral nerve that promote effective axonal regeneration by examining the effect of antibodies that interfere with the activity of previously described neurite growth-promoting factors. Axonal elongation over sciatic nerve tissue was found to be sensitive to the inhibitory effects of INO (for inhibitor of neurite outgrowth), a monoclonal antibody that recognizes and inhibits a neurite growth-promoting activity from PC-12 cell-conditioned medium. The INO antigen appears to be a molecular complex of laminin and heparan sulfate proteoglycan. In contrast, a rabbit antiserum that recognizes laminin purified from mouse Engelbreth-Holm-Swarm (EHS) sarcoma, stains the Schwann cell basal lamina of peripheral nerve, and inhibits neurite growth over purified laminin substrata has no detectable effect on the rate of axonal regeneration in our assay.

  4. Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways.

    PubMed

    Wu, Song-Di; Xia, Feng; Lin, Xue-Mei; Duan, Kang-Li; Wang, Fang; Lu, Qing-Li; Cao, Huan; Qian, Yi-Hua; Shi, Ming

    2016-01-01

    Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng's biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 μM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways. PMID:26840295

  5. Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways

    PubMed Central

    Wu, Song-Di; Xia, Feng; Lin, Xue-Mei; Duan, Kang-Li; Wang, Fang; Lu, Qing-Li; Cao, Huan; Qian, Yi-Hua; Shi, Ming

    2016-01-01

    Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng’s biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 μM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways. PMID:26840295

  6. Finite element analysis of the Arquin-designed CMU wall under a dynamic (blast) load.

    SciTech Connect

    Lopez, Carlos; Petti, Jason P.

    2008-12-01

    The Arquin Corporation designed a CMU (concrete masonry unit) wall construction and reinforcement technique that includes steel wire and polymer spacers that is intended to facilitate a faster and stronger wall construction. Since the construction method for an Arquin-designed wall is different from current wall construction practices, finite element computer analyses were performed to estimate the ability of the wall to withstand a hypothetical dynamic load, similar to that of a blast from a nearby explosion. The response of the Arquin wall was compared to the response of an idealized standard masonry wall exposed to the same dynamic load. Results from the simulations show that the Arquin wall deformed less than the idealized standard wall under such loading conditions. As part of a different effort, Sandia National Laboratories also looked at the relative static response of the Arquin wall, results that are summarized in a separate SAND Report.

  7. Dynamics of dual-polarization VCSEL-based optical frequency combs under optical injection locking.

    PubMed

    Prior, E; de Dios, C; Criado, R; Ortsiefer, M; Meissner, P; Acedo, P

    2016-09-01

    The present experimental work studies the dynamics of dual-polarization optical frequency combs (OFCs) based on gain switching (GS) vertical-cavity surface-emitting laser (VCSEL) diodes under optical injection locking (OIL). This study presents two main results. First, we have obtained an overall comb formed by two orthogonally polarized sub-combs with comparable span and power. The overall comb shows enhanced optical span and flatness and high coherence between its modes. The second result is that we have been able to control the polarization state of the overall comb by tuning the polarization state of the injected light by locking the same single teeth of the comb. This produces an overall comb with single polarization that is parallel or orthogonal. These are novel findings that provide for the development of efficient and compact OFCs based on GS VCSEL sources with versatile polarization dynamics. PMID:27607978

  8. Non-equilibrium dynamics of magnetically anisotropic particles under oscillating fields.

    PubMed

    Steinbach, Gabi; Gemming, Sibylle; Erbe, Artur

    2016-07-01

    In this article, we demonstrate how magnetic anisotropy of colloidal particles can give rise to unusual dynamics and controllable rearrangements under time-dependent fields. As an example, we study spherical particles with a radially off-centered net magnetic moment in an oscillating field. Based on complementary data from a numerical simulation of spheres with shifted dipole and experimental observations from particles with hemispherical ferromagnetic coating, it is explained on a two particle basis how this magnetic anisotropy causes nontrivial rotational motion and magnetic reorientation. We further present the behavior of larger ensembles of coated particles. It illustrates the potential for controlled reconfiguration based on the presented two-particle dynamics. PMID:27412618

  9. Mechanisms underlying skilled anticipation and recognition in a dynamic and temporally constrained domain.

    PubMed

    North, Jamie S; Ward, Paul; Ericsson, Anders; Williams, A Mark

    2011-02-01

    We examined the mechanisms underlying skilled anticipation and recognition in a dynamic, interactive, and temporally constrained domain. Skilled and less-skilled participants viewed dynamic film stimuli, anticipated event outcome, and provided immediate retrospective verbal reports. Previously viewed and novel sequences were then presented in film or point-light display format. Participants made recognition judgements and again gave retrospective verbal reports on their thought processes. Skilled participants demonstrated superior anticipation accuracy and were more sensitive in distinguishing previously seen from novel stimuli than less-skilled participants. Skilled participants utilised more complex memory representations than less-skilled individuals, as indicated by references in their retrospective reports to more evaluation and prediction statements. The representations activated during anticipation were more complex than those for recognition judgements in both groups. Findings are discussed with reference to long-term working memory theory. PMID:21294038

  10. Application of a nanosecond laser pulse to evaluate dynamic hardness under ultra-high strain rate

    NASA Astrophysics Data System (ADS)

    Radziejewska, Joanna

    2016-04-01

    The paper presents results of experimental tests of plastic metals deformation generated by a shock wave induced by laser pulse. Tests were carried out on the Nd:YAG laser with a wavelength of 1064 nm and the laser pulse of 10 ns duration. The shock wave generate by the laser pulse was used to induced local plastic deformation of the material surface. The study examined the possibility of application the process to develop a new method of measuring the dynamic hardness of materials under ultra-high strain rate. It has been shown that the shock wave induced by the laser pulse with an energy of 0.35-1.22 J causes a repeatable plastic deformation of surface of commercially available metals and alloys without thermal effects on the surfaces. Based on the knowledge of an imprint geometry, it is possible to evaluate the dynamic hardness of materials at strain rate in the range of 107 s-1.

  11. Dynamic testing of concrete under high confined pressure. Influence of saturation ratio and aggregate size

    NASA Astrophysics Data System (ADS)

    Forquin, P.; Piotrowska, E.; Gary, G.

    2015-09-01

    Concrete structures can be exposed to intense pressure loadings such as projectile-impact or detonation near a concrete structural element. To investigate the mechanical behaviour of concrete under high confining pressure, dynamic quasi-oedometric compression tests have been performed with a large diameter (80 mm) Split Hopkinson Pressure Bar apparatus. The concrete sample is placed within a steel confining ring and compressed along its axial direction. Hydrostatic pressures as high as 800 MPa and axial strain of about - 10% are reached during the tests. In the present work, experiments have been conducted on two types of concrete: MB50 microconcrete with a maximum grain size of 2 mm and R30A7 ordinary concrete of maximum grain size about 8 mm. Both concretes are tested in dry or saturated conditions. According to these dynamic experiments it is noted that grain size has a small influence whereas water content has a strong effect on the confined behaviour of concrete.

  12. Spin dynamics of an individual Cr atom in a semiconductor quantum dot under optical excitation

    NASA Astrophysics Data System (ADS)

    Lafuente-Sampietro, A.; Utsumi, H.; Boukari, H.; Kuroda, S.; Besombes, L.

    2016-08-01

    We studied the spin dynamics of a Cr atom incorporated in a II-VI semiconductor quantum dot using photon correlation techniques. We used recently developed singly Cr-doped CdTe/ZnTe quantum dots to access the spin of an individual magnetic atom. Auto-correlation of the photons emitted by the quantum dot under continuous wave optical excitation reveals fluctuations of the localized spin with a timescale in the 10 ns range. Cross-correlation gives quantitative transfer time between Cr spin states. A calculation of the time dependence of the spin levels population in Cr-doped quantum dots shows that the observed spin dynamics is dominated by the exciton-Cr interaction. These measurements also provide a lower bound in the 20 ns range for the intrinsic Cr spin relaxation time.

  13. Dynamics of mechanical feedback-type hydraulic servomotors under inertia loads

    NASA Technical Reports Server (NTRS)

    Gold, Harold; Otto, Edward W; Ransom, Victor L

    1953-01-01

    An analysis of the dynamics of mechanical feedback-type hydraulic servomotors under inertia loads is developed and experimental verification is presented. The analysis, which is developed in terms of two physical parameters, yields direct expressions for the following dynamic responses: (1) the transient response to a step input and the maximum cylinder pressure during the transient and (2) the variation of amplitude attenuation and phase shift with the frequency of a sinusoidally varying input. The validity of the analysis is demonstrated by means of recorded transient and frequency responses obtained on two servomotors. The calculated responses are in close agreement with the measured responses. The relations presented are readily applicable to the design as well as to the analysis of hydraulic servomotors.

  14. Decay dynamics of N2O under the impact of fast electrons

    NASA Astrophysics Data System (ADS)

    Khan, Arnab; Misra, Deepankar

    2016-03-01

    We experimentally investigate the two- and three-body breakup dynamics of N2O{}q+ (q=2,3) under the impact of fast (5 keV) electrons using a coincidence momentum spectroscopy technique. The kinetic energy release (KER) distributions have been derived from the measured momenta for various breakup channels. The present values are found to be quite different from a previously reported high energy electron impact study. From the measured momentum vectors, the geometry of the precursor molecular ion prior to the fragmentation has been reconstructed. The three-body decay dynamics of N2O3+ has been studied using Dalitz plots and Newton diagrams with a view of concerted and sequential decay mechanisms. It is found that the sequential process is present along with the concerted process for the N2O3+ \\to N+ + NO2+ \\quad \\to N+ + N+ + O+ channel.

  15. Complex network analysis of phase dynamics underlying oil-water two-phase flows.

    PubMed

    Gao, Zhong-Ke; Zhang, Shan-Shan; Cai, Qing; Yang, Yu-Xuan; Jin, Ning-De

    2016-01-01

    Characterizing the complicated flow behaviors arising from high water cut and low velocity oil-water flows is an important problem of significant challenge. We design a high-speed cycle motivation conductance sensor and carry out experiments for measuring the local flow information from different oil-in-water flow patterns. We first use multivariate time-frequency analysis to probe the typical features of three flow patterns from the perspective of energy and frequency. Then we infer complex networks from multi-channel measurements in terms of phase lag index, aiming to uncovering the phase dynamics governing the transition and evolution of different oil-in-water flow patterns. In particular, we employ spectral radius and weighted clustering coefficient entropy to characterize the derived unweighted and weighted networks and the results indicate that our approach yields quantitative insights into the phase dynamics underlying the high water cut and low velocity oil-water flows. PMID:27306101

  16. Comparative explorations of the revival and robustness for quantum dynamics under decoherence channels

    NASA Astrophysics Data System (ADS)

    Shi, Jia-Dong; Wang, Dong; Ye, Liu

    2016-04-01

    In this paper, we demonstrate the revival and robustness of quantum dynamics under local decoherent evolutions through investigating the dynamical behaviors of quantum correlation. The results show that in depolarizing channel, quantum discord damps faster and revivals after a dark interval of time, while the others will revival immediately at the critical point. In addition, in hybrid channel the declining initial condition can speed up the attenuation of quantum discord within a limited time, while it can enable trace distance discord and Bures distance discord to damp more smoothly. In this sense, quantum discord is typically less robust against decoherence than the others. Interestingly, nonlocality shows different decay rates in the vicinity of critical point. Additionally, we lastly provide a physical interpretation concerning these phenomena.

  17. Gain recovery dynamics in semiconductor optical amplifiers with distributed feedback grating under assist light injection

    NASA Astrophysics Data System (ADS)

    Qin, Cui; Zhao, Jing; Yu, Huilong; Zhang, Jian

    2016-07-01

    The gain recovery dynamic characteristics of the semiconductor optical amplifier (SOA) with distributed feedback (DFB) grating are theoretically investigated. The interaction of the grating structure and the assist light is used to accelerate the gain recovery process in the SOA. The effects of the assist light that is injected into the SOA with DFB structure on the gain recovery dynamics, the steady-state carrier density, and field intensity distributions are analyzed, respectively. Results show that the recovery time in the DFB SOA is successfully reduced by injecting relatively high power assist light, whose wavelength is set at the gain region. Finally, under assist light injection, the effects of DFB grating on the gain recovery process are also discussed. It is shown that the gain recovery in the SOA with DFB grating is faster than that in the SOA without DFB grating. In addition, the coupling factor in the DFB grating structure can be optimized to shorten the gain recovery time.

  18. Complex network analysis of phase dynamics underlying oil-water two-phase flows

    PubMed Central

    Gao, Zhong-Ke; Zhang, Shan-Shan; Cai, Qing; Yang, Yu-Xuan; Jin, Ning-De

    2016-01-01

    Characterizing the complicated flow behaviors arising from high water cut and low velocity oil-water flows is an important problem of significant challenge. We design a high-speed cycle motivation conductance sensor and carry out experiments for measuring the local flow information from different oil-in-water flow patterns. We first use multivariate time-frequency analysis to probe the typical features of three flow patterns from the perspective of energy and frequency. Then we infer complex networks from multi-channel measurements in terms of phase lag index, aiming to uncovering the phase dynamics governing the transition and evolution of different oil-in-water flow patterns. In particular, we employ spectral radius and weighted clustering coefficient entropy to characterize the derived unweighted and weighted networks and the results indicate that our approach yields quantitative insights into the phase dynamics underlying the high water cut and low velocity oil-water flows. PMID:27306101

  19. A dynamic marker of very short-term heartbeat under pathological states via network analysis

    NASA Astrophysics Data System (ADS)

    Hou, Feng-Zhen; Wang, Jun; Wu, Xiao-Chuan; Yan, Fang-Rong

    2014-09-01

    We developed a novel network to probe pathological states with the aid of heartbeat time series, by regarding each vector in the embedding phase space as one node of the network and using a permutation-based measure to determine links between nodes. The entropy of the degree distribution (E_{{DD}}) of the network shows a general and significant reduction under pathological conditions, even when there are only ultra short-term heartbeats (\\approx 50\\text{ beats}) available. The reduction of E_{{DD}} is possibly a dynamic marker of cardiac disorders. Our results reveal that a comparatively strong “memory” should usually exist in the healthy cardiovascular system whereas it dramatically declines when a cardiac disease is arising. The proposed method shows great promise in screening cardiac diseases and monitoring dynamic changes of the autonomic nervous system. Besides, as a universal method for analyzing the time series, the proposed approach seems to be promising also for other research disciplines.

  20. Complex network analysis of phase dynamics underlying oil-water two-phase flows

    NASA Astrophysics Data System (ADS)

    Gao, Zhong-Ke; Zhang, Shan-Shan; Cai, Qing; Yang, Yu-Xuan; Jin, Ning-De

    2016-06-01

    Characterizing the complicated flow behaviors arising from high water cut and low velocity oil-water flows is an important problem of significant challenge. We design a high-speed cycle motivation conductance sensor and carry out experiments for measuring the local flow information from different oil-in-water flow patterns. We first use multivariate time-frequency analysis to probe the typical features of three flow patterns from the perspective of energy and frequency. Then we infer complex networks from multi-channel measurements in terms of phase lag index, aiming to uncovering the phase dynamics governing the transition and evolution of different oil-in-water flow patterns. In particular, we employ spectral radius and weighted clustering coefficient entropy to characterize the derived unweighted and weighted networks and the results indicate that our approach yields quantitative insights into the phase dynamics underlying the high water cut and low velocity oil-water flows.

  1. A triphasic constrained mixture model of engineered tissue formation under in vitro dynamic mechanical conditioning.

    PubMed

    Soares, Joao S; Sacks, Michael S

    2016-04-01

    While it has become axiomatic that mechanical signals promote in vitro engineered tissue formation, the underlying mechanisms remain largely unknown. Moreover, efforts to date to determine parameters for optimal extracellular matrix (ECM) development have been largely empirical. In the present work, we propose a two-pronged approach involving novel theoretical developments coupled with key experimental data to develop better mechanistic understanding of growth and development of dense connective tissue under mechanical stimuli. To describe cellular proliferation and ECM synthesis that occur at rates of days to weeks, we employ mixture theory to model the construct constituents as a nutrient-cell-ECM triphasic system, their transport, and their biochemical reactions. Dynamic conditioning protocols with frequencies around 1 Hz are described with multi-scale methods to couple the dissimilar time scales. Enhancement of nutrient transport due to pore fluid advection is upscaled into the growth model, and the spatially dependent ECM distribution describes the evolving poroelastic characteristics of the scaffold-engineered tissue construct. Simulation results compared favorably to the existing experimental data, and most importantly, distinguish between static and dynamic conditioning regimes. The theoretical framework for mechanically conditioned tissue engineering (TE) permits not only the formulation of novel and better-informed mechanistic hypothesis describing the phenomena underlying TE growth and development, but also the exploration/optimization of conditioning protocols in a rational manner. PMID:26055347

  2. Dynamics of Concentrated Silica Suspension under Oscillatory Shear Studied by SAXS and XPCS

    NASA Astrophysics Data System (ADS)

    Lee, Jonghun; Lin, Xiao-Min; Sandy, Alec; Narayanan, Suresh; X-ray Science Division Team; CenterNanomaterials Team

    2015-03-01

    The viscoelastic properties of complex fluids are often obtained by applying small amplitude oscillatory shear (SAOS). In this regime, their microstructure does not change by shear, and the shear stress linearly responds to the applied strain. However, in the real application, high shear strain or rate is applied, where the viscoelastic properties are affected by the microstructural deformation by this high shear. The rheological behavior of complex fluids under large amplitude oscillatory shear (LAOS) has been widely studied, but there is a lack of studies in microscopic dynamics of complex fluids under LAOS. X-ray scattering is a suitable method to understand microscopic perspective of rheology because of its proper length scales of tens to hundreds nm and time scales of millisecond to thousands second. Here, we studied the dynamics of the concentrated silica nanoparticle suspensions in PEG under different shear strain regimes using small angle x-ray scattering (SAXS) and x-ray photon correlation spectroscopy (XPCS). With strain increasing, these suspensions showed shear thinning and shear thickening behavior, and their microstructural change was observed by SAXS. In oscillatory shear, as the original scattering volume periodically comes back to the original position, we could better study the changes in autocorrelation function by shear and diffusion than steady shear study where correlation decays by transit.

  3. Existence, stability, and nonlinear dynamics of detached Bridgman growth states under zero gravity

    NASA Astrophysics Data System (ADS)

    Yeckel, Andrew; Derby, Jeffrey J.

    2011-01-01

    A thermocapillary model is used to study the existence, stability, and nonlinear dynamics of detached melt crystal growth in a vertical Bridgman system under zero gravity conditions. The model incorporates time-dependent heat, mass, and momentum transport, and accounts for temperature-dependent surface tension effects at the menisci bounding the melt. The positions of the menisci and phase-change boundary are computed to satisfy the conservation laws rigorously. A rich bifurcation structure in gap width versus pressure difference is uncovered, demarcating conditions under which growth with a stable gap is feasible. Thermal effects shift the bifurcation diagram to a slightly different pressure range, but do not alter its general structure. Necking and freeze-off are shown to be two different manifestations of the same instability mechanism. Supercooling of melt at the meniscus and low thermal gradients in the melt ahead of the crystal-melt-gas triple phase line, either of which may be destabilizing, are both observed under some conditions. The role of wetting and growth angles in dynamic shape stability is clarified.

  4. Dynamical instability induced by the zero mode under symmetry breaking external perturbation

    SciTech Connect

    Takahashi, J. Nakamura, Y. Yamanaka, Y.

    2014-08-15

    A complex eigenvalue in the Bogoliubov–de Gennes equations for a stationary Bose-Einstein condensate in the ultracold atomic system indicates the dynamical instability of the system. We also have the modes with zero eigenvalues for the condensate, called the zero modes, which originate from the spontaneous breakdown of symmetries. Although the zero modes are suppressed in many theoretical analyses, we take account of them in this paper and argue that a zero mode can change into one with a pure imaginary eigenvalue by applying a symmetry breaking external perturbation potential. This emergence of a pure imaginary mode adds a new type of scenario of dynamical instability to that characterized by the complex eigenvalue of the usual excitation modes. For illustration, we deal with two one-dimensional homogeneous Bose–Einstein condensate systems with a single dark soliton under a respective perturbation potential, breaking the invariance under translation, to derive pure imaginary modes. - Highlights: • Zero modes are important but ignored in many theories for the cold atomic system. • We discuss the zero mode under symmetry breaking potential in this system. • We consider the zero mode of translational invariance for a single dark soliton. • We show that it turns into an anomalous or pure imaginary mode.

  5. Saturated sodium chloride solution under an external static electric field: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Ren, Gan; Wang, Yan-Ting

    2015-12-01

    The behavior of saturated aqueous NaCl solutions under a constant external electric field (E) was studied by molecular dynamics (MD) simulation. Our dynamic MD simulations indicated that the irreversible nucleation process towards crystallization is accelerated by a moderate E but retarded or even prohibited under a stronger E, which can be understood by the competition between self-diffusion and drift motion. The former increases with E, thereby accelerating the nucleation process, whereas the latter pulls oppositely charged ions apart under a stronger E, thereby decelerating nucleation. Additionally, our steady-state MD simulations indicated that a first-order phase transition occurs in saturated solutions at a certain threshold Ec. The magnitude of Ec increases with concentration because larger clusters form more easily when the solution is more concentrated and require a stronger E to dissociate. Project supported by the National Basic Research Program of China (Grant No. 2013CB932804) and the National Natural Science Foundation of China (Grant Nos. 91227115, 11274319, and 11421063).

  6. Simulation of Space Charge Dynamic in Polyethylene Under DC Continuous Electrical Stress

    NASA Astrophysics Data System (ADS)

    Hamed, Boukhari; Rogti, Fatiha

    2016-06-01

    The space charge dynamic plays a very important role in the aging and breakdown of polymeric insulation materials under high voltage. This is due to the intensification of the local electric field and the attendant chemical-mechanical effects in the vicinity around the trapped charge. In this paper, we have investigated the space charge dynamic in low-density polyethylene under high direct-current voltage, which is evaluated by experimental conditions. The evaluation is on the basis of simulation using a bipolar charge transport model consisting of charge injection, transports, trapping, detrapping, and recombination phenomena. The theoretical formulation of the physical problem is based on the Poisson, the continuity, and the transport equations. Numerical results provide temporal and local distributions of the electric field, the space charge density for the different kinds of charges (net charge density, mobile and trapped of electron density, mobile hole density), conduction and displacement current densities, and the external current. The result shows the appearance of the negative packet-like space charge with a large amount of the bulk under the dc electric field of 100 kV/mm, and the induced distortion of the electric field is largely near to the anode, about 39% higher than the initial electric field applied.

  7. Autophagy inhibition in endogenous and nutrient-deprived conditions reduces dorsal root ganglia neuron survival and neurite growth in vitro.

    PubMed

    Clarke, Joseph-Patrick; Mearow, Karen

    2016-07-01

    Peripheral neuropathies can result in cytoskeletal changes in axons, ultimately leading to Wallerian degeneration and cell death. Recently, autophagy has been studied as a potential target for improving axonal survival and growth during peripheral nerve damage. This study investigates the influence of autophagy on adult dorsal root ganglia (DRG) neuron survival and axonal growth under control and nutrient deprivation conditions. Constitutive autophagy was modulated with pharmacological activators (rapamycin; Rapa) and inhibitors (3-methyladenine, bafilomycin A1) in conjunction with either a nutrient-stable environment (standard culture medium) or a nutrient-deprived environment (Hank's balanced salt solution + Ca(2+) /Mg(2+) ). The results demonstrated that autophagy inhibition decreased cell viability and reduced neurite growth and branching complexity. Although