The time-dependent response of 3- and 5-layer sandwich beams

NASA Technical Reports Server (NTRS)

Hyer, M. W.; Oleksuk, L. S. S.; Bowles, D. E.

1992-01-01

Simple sandwich beam models have been developed to study the effect of the time-dependent constitutive properties of fiber-reinforced polymer matrix composites, considered for use in orbiting precision segmented reflectors, on the overall deformations. The 3- and 5-layer beam models include layers representing the face sheets, the core, and the adhesive. The static elastic deformation response of the sandwich beam models to a midspan point load is studied using the principle of stationary potential energy. In addition to quantitative conclusions, several assumptions are discussed which simplify the analysis for the case of more complicated material models. It is shown that the simple three-layer model is sufficient in many situations.

Shapes matter: examining the optical response evolution in stretched aluminium nanoparticles via time-dependent density functional theory.

PubMed

Mokkath, Junais Habeeb

2017-12-20

Using first-principles time-dependent density functional theory calculations, we investigate the shape-anisotropy effects on the optical response of a spherical aluminium nanoparticle subjected to a stretching process in different directions. Progressively increased stretching in one direction resulted in prolate spheroid (nanorice) geometries and produced a couple of well-distinguishable dominant peaks together with some satellite peaks in the UV-visible region of the electromagnetic spectrum. On the other hand, progressively increased stretching in two directions caused multiple peaks to appear in the UV-visible region of the electromagnetic spectrum. We believe that our findings can be beneficial for the emerging and potentially far-reaching field of aluminum plasmonics.

Voltage-Clamp Studies on Uterine Smooth Muscle

PubMed Central

Anderson, Nels C.

1969-01-01

These studies have developed and tested an experimental approach to the study of membrane ionic conductance mechanisms in strips of uterine smooth muscle. The experimental and theoretical basis for applying the double sucrose-gap technique is described along with the limitations of this system. Nonpropagating membrane action potentials were produced in response to depolarizing current pulses under current-clamp conditions. The stepwise change of membrane potential under voltage-clamp conditions resulted in a family of ionic currents with voltage- and time-dependent characteristics. In sodium-free solution the peak transient current decreased and its equilibrium potential shifted along the voltage axis toward a more negative internal potential. These studies indicate a sodium-dependent, regenerative excitation mechanism. PMID:5796366

Time-dependent local potential in a Tomonaga-Luttinger liquid

NASA Astrophysics Data System (ADS)

Kamar, Naushad Ahmad; Giamarchi, Thierry

2017-12-01

We study the energy deposition in a one-dimensional interacting quantum system with a pointlike potential modulated in amplitude. The pointlike potential at position x =0 has a constant part and a small oscillation in time with a frequency ω . We use bosonization, renormalization group, and linear response theory to calculate the corresponding energy deposition. It exhibits a power law behavior as a function of the frequency that reflects the Tomonaga-Luttinger liquid (TLL) nature of the system. Depending on the interactions in the system, characterized by the TLL parameter K of the system, a crossover between weak and strong coupling for the backscattering due to the potential is possible. We compute the frequency scale ω*, at which such crossover exists. We find that the energy deposition due to the backscattering shows different exponents for K >1 and K <1 . We discuss possible experimental consequences, in the context of cold atomic gases, of our theoretical results.

Reconstruction of the action potential of ventricular myocardial fibres

PubMed Central

Beeler, G. W.; Reuter, H.

1977-01-01

1. A mathematical model of membrane action potentials of mammalian ventricular myocardial fibres is described. The reconstruction model is based as closely as possible on ionic currents which have been measured by the voltage-clamp method. 2. Four individual components of ionic current were formulated mathematically in terms of Hodgkin—Huxley type equations. The model incorporates two voltage- and time-dependent inward currents, the excitatory inward sodium current, iNa, and a secondary or slow inward current, is, primarily carried by calcium ions. A time-independent outward potassium current, iK1, exhibiting inward-going rectification, and a voltage- and time-dependent outward current, ix1, primarily carried by potassium ions, are further elements of the model. 3. The iNa is primarily responsible for the rapid upstroke of the action potential, while the other current components determine the configuration of the plateau of the action potential and the re-polarization phase. The relative importance of inactivation of is and of activation of ix1 for termination of the plateau is evaluated by the model. 4. Experimental phenomena like slow recovery of the sodium system from inactivation, frequency dependence of the action potential duration, all-or-nothing re-polarization, membrane oscillations are adequately described by the model. 5. Possible inadequacies and shortcomings of the model are discussed. PMID:874889

Dopamine D1 Receptors Regulate the Light Dependent Development of Retinal Synaptic Responses

PubMed Central

He, Quanhua; Xu, Hong-ping; Wang, Ping; Tian, Ning

2013-01-01

Retinal synaptic connections and function are developmentally regulated. Retinal synaptic activity plays critical roles in the development of retinal synaptic circuitry. Dopamine receptors have been thought to play important roles in the activity-dependent synaptic plasticity in central nervous system. The primary goal of this study is to determine whether dopamine D1 receptor regulates the activity-dependent development of retinal light responsiveness. Accordingly, we recorded electroretinogram from wild type mice and mice with genetic deletion of D1 dopamine receptor (D1−/− mice) raised under cyclic light conditions and constant darkness. Our results demonstrated that D1−/− mice have reduced amplitudes of all three major components of electroretinogram in adulthood. When the relative strength of the responses is considered, the D1−/− mice have selective reduction of the amplitudes of a-wave and oscillatory potentials evoked by low-intermediate intensities of lights. During postnatal development, D1−/− mice have increased amplitude of b-wave at the time of eye-opening but reduced developmental increase of the amplitude of b-wave after eye opening. Light deprivation from birth significantly reduced the amplitudes of b-wave and oscillatory potentials, increased the outer retinal light response gain and altered the light response kinetics of both a- and b-waves of wild type mice. In D1−/− mice, the effect of dark rearing on the amplitude of oscillatory potentials was diminished and dark rearing induced effects on the response gain of outer retina and the kinetics of a-wave were reversed. These results demonstrated roles of dopamine D1 receptor in the activity-dependent functional development of mouse retina. PMID:24260267

Detecting changes in dynamic and complex acoustic environments

PubMed Central

Boubenec, Yves; Lawlor, Jennifer; Górska, Urszula; Shamma, Shihab; Englitz, Bernhard

2017-01-01

Natural sounds such as wind or rain, are characterized by the statistical occurrence of their constituents. Despite their complexity, listeners readily detect changes in these contexts. We here address the neural basis of statistical decision-making using a combination of psychophysics, EEG and modelling. In a texture-based, change-detection paradigm, human performance and reaction times improved with longer pre-change exposure, consistent with improved estimation of baseline statistics. Change-locked and decision-related EEG responses were found in a centro-parietal scalp location, whose slope depended on change size, consistent with sensory evidence accumulation. The potential's amplitude scaled with the duration of pre-change exposure, suggesting a time-dependent decision threshold. Auditory cortex-related potentials showed no response to the change. A dual timescale, statistical estimation model accounted for subjects' performance. Furthermore, a decision-augmented auditory cortex model accounted for performance and reaction times, suggesting that the primary cortical representation requires little post-processing to enable change-detection in complex acoustic environments. DOI: http://dx.doi.org/10.7554/eLife.24910.001 PMID:28262095

ac-driven vortices and the Hall effect in a superconductor with a tilted washboard pinning potential

NASA Astrophysics Data System (ADS)

Shklovskij, Valerij A.; Dobrovolskiy, Oleksandr V.

2008-09-01

The Langevin equation for a two-dimensional (2D) nonlinear guided vortex motion in a tilted cosine pinning potential in the presence of an ac is exactly solved in terms of a matrix continued fraction at arbitrary value of the Hall effect. The influence of an ac of arbitrary amplitude and frequency on the dc and ac magnetoresistivity tensors is analyzed. The ac density and frequency dependence of the overall shape and the number and position of the Shapiro steps on the anisotropic current-voltage characteristics are considered. The influence of a subcritical or overcritical dc on the time-dependent stationary ac longitudinal and transverse resistive vortex responses (on the frequency of an ac drive Ω ) in terms of the nonlinear impedance tensor Ẑ and the nonlinear ac response at Ω harmonics are studied. Analytical formulas for 2D temperature-dependent linear impedance tensor ẐL in the presence of a dc which depend on the angle α between the current-density vector and the guiding direction of the washboard planar pinning potential are derived and analyzed. Influence of α anisotropy and the Hall effect on the nonlinear power absorption by vortices is discussed.

Predicting invasive species impacts: a community module functional response approach reveals context dependencies.

PubMed

Paterson, Rachel A; Dick, Jaimie T A; Pritchard, Daniel W; Ennis, Marilyn; Hatcher, Melanie J; Dunn, Alison M

2015-03-01

Predatory functional responses play integral roles in predator-prey dynamics, and their assessment promises greater understanding and prediction of the predatory impacts of invasive species. Other interspecific interactions, however, such as parasitism and higher-order predation, have the potential to modify predator-prey interactions and thus the predictive capability of the comparative functional response approach. We used a four-species community module (higher-order predator; focal native or invasive predators; parasites of focal predators; native prey) to compare the predatory functional responses of native Gammarus duebeni celticus and invasive Gammarus pulex amphipods towards three invertebrate prey species (Asellus aquaticus, Simulium spp., Baetis rhodani), thus, quantifying the context dependencies of parasitism and a higher-order fish predator on these functional responses. Our functional response experiments demonstrated that the invasive amphipod had a higher predatory impact (lower handling time) on two of three prey species, which reflects patterns of impact observed in the field. The community module also revealed that parasitism had context-dependent influences, for one prey species, with the potential to further reduce the predatory impact of the invasive amphipod or increase the predatory impact of the native amphipod in the presence of a higher-order fish predator. Partial consumption of prey was similar for both predators and occurred increasingly in the order A. aquaticus, Simulium spp. and B. rhodani. This was associated with increasing prey densities, but showed no context dependencies with parasitism or higher-order fish predator. This study supports the applicability of comparative functional responses as a tool to predict and assess invasive species impacts incorporating multiple context dependencies. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

Quasi-static responses and variational principles in gradient plasticity

NASA Astrophysics Data System (ADS)

Nguyen, Quoc-Son

2016-12-01

Gradient models have been much discussed in the literature for the study of time-dependent or time-independent processes such as visco-plasticity, plasticity and damage. This paper is devoted to the theory of Standard Gradient Plasticity at small strain. A general and consistent mathematical description available for common time-independent behaviours is presented. Our attention is focussed on the derivation of general results such as the description of the governing equations for the global response and the derivation of related variational principles in terms of the energy and the dissipation potentials. It is shown that the quasi-static response under a loading path is a solution of an evolution variational inequality as in classical plasticity. The rate problem and the rate minimum principle are revisited. A time-discretization by the implicit scheme of the evolution equation leads to the increment problem. An increment of the response associated with a load increment is a solution of a variational inequality and satisfies also a minimum principle if the energy potential is convex. The increment minimum principle deals with stables solutions of the variational inequality. Some numerical methods are discussed in view of the numerical simulation of the quasi-static response.

Graph-Based Semantic Web Service Composition for Healthcare Data Integration.

PubMed

Arch-Int, Ngamnij; Arch-Int, Somjit; Sonsilphong, Suphachoke; Wanchai, Paweena

2017-01-01

Within the numerous and heterogeneous web services offered through different sources, automatic web services composition is the most convenient method for building complex business processes that permit invocation of multiple existing atomic services. The current solutions in functional web services composition lack autonomous queries of semantic matches within the parameters of web services, which are necessary in the composition of large-scale related services. In this paper, we propose a graph-based Semantic Web Services composition system consisting of two subsystems: management time and run time. The management-time subsystem is responsible for dependency graph preparation in which a dependency graph of related services is generated automatically according to the proposed semantic matchmaking rules. The run-time subsystem is responsible for discovering the potential web services and nonredundant web services composition of a user's query using a graph-based searching algorithm. The proposed approach was applied to healthcare data integration in different health organizations and was evaluated according to two aspects: execution time measurement and correctness measurement.

Graph-Based Semantic Web Service Composition for Healthcare Data Integration

PubMed Central

2017-01-01

Within the numerous and heterogeneous web services offered through different sources, automatic web services composition is the most convenient method for building complex business processes that permit invocation of multiple existing atomic services. The current solutions in functional web services composition lack autonomous queries of semantic matches within the parameters of web services, which are necessary in the composition of large-scale related services. In this paper, we propose a graph-based Semantic Web Services composition system consisting of two subsystems: management time and run time. The management-time subsystem is responsible for dependency graph preparation in which a dependency graph of related services is generated automatically according to the proposed semantic matchmaking rules. The run-time subsystem is responsible for discovering the potential web services and nonredundant web services composition of a user's query using a graph-based searching algorithm. The proposed approach was applied to healthcare data integration in different health organizations and was evaluated according to two aspects: execution time measurement and correctness measurement. PMID:29065602

The development and use of a molecular model for soybean maturity groups

USDA-ARS?s Scientific Manuscript database

Achieving appropriate maturity in a target environment is essential to maximizing crop yield potential. In soybean [Glycine max (L.) Merr.], the time to maturity is largely dependent on developmental response to dark periods. Once the critical photoperiod is reached, flowering is initiated and rep...

Contamination of current-clamp measurement of neuron capacitance by voltage-dependent phenomena

PubMed Central

White, William E.

2013-01-01

Measuring neuron capacitance is important for morphological description, conductance characterization, and neuron modeling. One method to estimate capacitance is to inject current pulses into a neuron and fit the resulting changes in membrane potential with multiple exponentials; if the neuron is purely passive, the amplitude and time constant of the slowest exponential give neuron capacitance (Major G, Evans JD, Jack JJ. Biophys J 65: 423–449, 1993). Golowasch et al. (Golowasch J, Thomas G, Taylor AL, Patel A, Pineda A, Khalil C, Nadim F. J Neurophysiol 102: 2161–2175, 2009) have shown that this is the best method for measuring the capacitance of nonisopotential (i.e., most) neurons. However, prior work has not tested for, or examined how much error would be introduced by, slow voltage-dependent phenomena possibly present at the membrane potentials typically used in such work. We investigated this issue in lobster (Panulirus interruptus) stomatogastric neurons by performing current clamp-based capacitance measurements at multiple membrane potentials. A slow, voltage-dependent phenomenon consistent with residual voltage-dependent conductances was present at all tested membrane potentials (−95 to −35 mV). This phenomenon was the slowest component of the neuron's voltage response, and failure to recognize and exclude it would lead to capacitance overestimates of several hundredfold. Most methods of estimating capacitance depend on the absence of voltage-dependent phenomena. Our demonstration that such phenomena make nonnegligible contributions to neuron responses even at well-hyperpolarized membrane potentials highlights the critical importance of checking for such phenomena in all work measuring neuron capacitance. We show here how to identify such phenomena and minimize their contaminating influence. PMID:23576698

Potentiation of capsaicin-induced neurogenic inflammation by 5-HT7 receptors in the rat hind paw: Involvement of calcitonin gen-related peptide.

PubMed

Arreola-Peralta, Luis D; Altamirano-Reyna, Frida; Galindo-González, Deni M; Solis-Anguiano, Jessica G; Lacivita, Enza; Leopoldo, Marcello; Terrón, José A

2018-05-03

A decrease in the activation threshold of primary sensory neurons to transient receptor potential V1 (TRPV1) stimulation by serotonin 5-HT7 receptors has been reported but no confirmation if this might translate into facilitation of neurogenic inflammation has been provided. We analysed the modulation of capsaicin (CAP)-induced neurogenic inflammation in the rat hind paw by the selective 5-HT7 receptor agonist, LP-44, and the involvement of calcitonin gen-related peptide (CGRP) in this effect. Animals received intra-plantar injections (30 μL) of vehicle, CAP (0.05%, 0.1% and 0.2%), LP-44 (7.5 and 15 nmol) and the combination of LP-44 + CAP; then, the time course of the inflammatory responses was measured. The effect of the 5-HT7 receptor antagonist, SB-269970 (3 mg/kg, s.c.), on responses produced by LP-44 alone and combined with CAP was tested. As expected, CAP produced concentration- and time-dependent inflammatory responses in the hind paw. Interestingly, LP-44 by itself also produced inflammation in a concentration- and time-dependent manner, and magnified CAP-induced responses. Systemic pre-treatment with SB-269970 significantly blunted LP-44 (15 nmol)-induced inflammation as well as magnified inflammatory responses produced by the combination of LP-44 (7.5 and 15 nmol) + CAP (0.1%) thus confirming the involvement of 5-HT7 receptors. Finally, the non-peptide CGRP receptor antagonist, BIBN4096 (3 mg/kg, s.c.), strongly inhibited the potentiated inflammatory responses induced by LP-44 (7.5 and 15 nmol) + CAP (0.1%) thus substantiating their neurogenic nature. Thus, sensitization of CAP-sensitive primary sensory neurons by 5-HT7 receptors may result in facilitation of neurogenic inflammation involving CGRP in the rat hind paw. Copyright © 2018. Published by Elsevier Inc.

Large plasma-membrane depolarization precedes rapid blue-light-induced growth inhibition in cucumber

NASA Technical Reports Server (NTRS)

Spalding, E. P.; Cosgrove, D. J.

1989-01-01

Blue-light (BL)-induced suppression of elongation of etiolated Cucumis sativus L. hypocotyls began after a 30-s lag time, which was halved by increasing the fluence rate from 10 to 100 micromoles m-2 s-1. Prior to the growth suppression, the plasma-membrane of the irradiated cells depolarized by as much as 100 mV, then returned within 2-3 min to near its initial value. The potential difference measured with surface electrodes changed with an identical time course but opposite polarity. The lag time for the change in surface potential showed an inverse dependence on fluence rate, similar to the lag for the growth inhibition. Green light and red light caused neither the electrical response nor the rapid inhibition of growth. The depolarization by BL did not propagate to nonirradiated regions and exhibited a refractory period of about 10 min following a BL pulse. Fluence-response relationships for the electrical and growth responses provide correlational evidence that the plasma-membrane depolarization reflects an event in the transduction chain of this light-growth response.

Using resistive readout to probe ultrafast dynamics of a plasmonic sensor

NASA Astrophysics Data System (ADS)

Cheney, Alec; Chen, Borui; Cartwright, Alexander; Thomay, Tim

2018-02-01

Surface plasmons in a DC current lead to an increase in scattering processes, resulting in a measurable increase in electrical resistance of a plasmonic nano-grating. This enables a purely electronic readout of plasmonically mediated optical absorption. We show that there is a time-dependence in these resistance changes on the order of 100ps that we attribute to electron-phonon and phonon-phonon scattering processes in the metal of the nano-gratings. Since plasmonic responses are strongly structurally dependent, an appropriately designed plasmoelectronic detector could potentially offer an extremely fast response at communication wavelengths in a fully CMOS compatible system.

Linear response and correlation of a self-propelled particle in the presence of external fields

NASA Astrophysics Data System (ADS)

Caprini, Lorenzo; Marini Bettolo Marconi, Umberto; Vulpiani, Angelo

2018-03-01

We study the non-equilibrium properties of non interacting active Ornstein-Uhlenbeck particles (AOUP) subject to an external nonuniform field using a Fokker-Planck approach with a focus on the linear response and time-correlation functions. In particular, we compare different methods to compute these functions including the unified colored noise approximation (UCNA). The AOUP model, described by the position of the particle and the active force acting on it, is usually mapped into a Markovian process, describing the motion of a fictitious passive particle in terms of its position and velocity, where the effect of the activity is transferred into a position-dependent friction. We show that the form of the response function of the AOUP depends on whether we put the perturbation on the position and keep unperturbed the active force in the original variables or perturb the position and maintain unperturbed the velocity in the transformed variables. Indeed, as a result of the change of variables the perturbation on the position becomes a perturbation both on the position and on the fictitious velocity. We test these predictions by considering the response for three types of convex potentials: quadratic, quartic and double-well potential. Moreover, by comparing the response of the AOUP model with the corresponding response of the UCNA model we conclude that although the stationary properties are fairly well approximated by the UCNA, the non equilibrium properties are not, an effect which is not negligible when the persistence time is large.

Wave function for time-dependent harmonically confined electrons in a time-dependent electric field.

PubMed

Li, Yu-Qi; Pan, Xiao-Yin; Sahni, Viraht

2013-09-21

The many-body wave function of a system of interacting particles confined by a time-dependent harmonic potential and perturbed by a time-dependent spatially homogeneous electric field is derived via the Feynman path-integral method. The wave function is comprised of a phase factor times the solution to the unperturbed time-dependent Schrödinger equation with the latter being translated by a time-dependent value that satisfies the classical driven equation of motion. The wave function reduces to that of the Harmonic Potential Theorem wave function for the case of the time-independent harmonic confining potential.

STRETCH-DEPENDENT SENSITIZATION OF POST-JUNCTIONAL NEURAL EFFECTORS IN COLONIC MUSCLES

PubMed Central

Won, Kyung-Jong; Sanders, Kenton M.; Ward, Sean M.

2012-01-01

Background The colon undergoes distension-induced changes in motor activity as luminal contents or feces increases wall pressure. Input from enteric motor neurons regulates motility. Here we examined stretch-dependent responses in circular muscle strips of murine colon. Methods Length-ramps (6–31μm s−1) were applied in the axis of the circular muscle layer in a controlled manner until 5 mN isometric force was reached. Key Results Length-ramps produced transient membrane potential hyperpolarizations and attenuation of action potential (AP) complexes. Responses were reproducible when ramps were applied every 30s. Stretch-dependent hyperpolarization was blocked by TTX, suggesting AP-dependent release of inhibitory neurotransmitter(s). Atropine did not potentiate stretch-induced hyperpolarizations, but increased compliance of the circular layer. L-NNA inhibited stretch-dependent hyperpolarization and decreased muscle compliance, suggesting release of NO mediates stretch-dependent inhibition. Control membrane potential was restored by the NO donor SNP. Stretch-dependent hyperpolarizations were blocked by L-methionine, an inhibitor of stretch-dependent K+ (SDK) channels in colonic muscles. Loss of ICC, elicited by Kit neutralizing antibody, also inhibited responses to stretch. In presence of L-NNA and apamin, stretch responses became excitatory and were characterized by membrane depolarization and increased AP firing. A neurokinin-1 receptor antagonist inhibited this stretch-dependent increase in excitability. Conclusions & Inferences Our data show that stretch-dependent responses in colonic muscles require tonic firing of enteric inhibitory neurons, but reflex activation of neurons does not appear to be necessary. NO causes activation of SDK channels, and stretch of muscles further activates these channels, explaining the inhibitory response to stretch in colonic muscle strips. PMID:23279087

Dynamic kinetic energy potential for orbital-free density functional theory.

PubMed

Neuhauser, Daniel; Pistinner, Shlomo; Coomar, Arunima; Zhang, Xu; Lu, Gang

2011-04-14

A dynamic kinetic energy potential (DKEP) is developed for time-dependent orbital-free (TDOF) density function theory applications. This potential is constructed to affect only the dynamical (ω ≠ 0) response of an orbital-free electronic system. It aims at making the orbital-free simulation respond in the same way as that of a noninteracting homogenous electron gas (HEG), as required by a correct kinetic energy, therefore enabling extension of the success of orbital-free density functional theory in the static case (e.g., for embedding and description of processes in bulk materials) to dynamic processes. The potential is constructed by expansions of terms, each of which necessitates only simple time evolution (concurrent with the TDOF evolution) and a spatial convolution at each time-step. With 14 such terms a good fit is obtained to the response of the HEG at a large range of frequencies, wavevectors, and densities. The method is demonstrated for simple jellium spheres, approximating Na(9)(+) and Na(65)(+) clusters. It is applicable both to small and large (even ultralarge) excitations and the results converge (i.e., do not blow up) as a function of time. An extension to iterative frequency-resolved extraction is briefly outlined, as well as possibly numerically simpler expansions. The approach could also be extended to fit, instead of the HEG susceptibility, either an experimental susceptibility or a theoretically derived one for a non-HEG system. The DKEP potential should be a powerful tool for embedding a dynamical system described by a more accurate method (such as time-dependent density functional theory, TDDFT) in a large background described by TDOF with a DKEP potential. The type of expansions used and envisioned should be useful for other approaches, such as memory functionals in TDDFT. Finally, an appendix details the formal connection between TDOF and TDDFT.

Optimized effective potential in real time: Problems and prospects in time-dependent density-functional theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mundt, Michael; Kuemmel, Stephan

2006-08-15

The integral equation for the time-dependent optimized effective potential (TDOEP) in time-dependent density-functional theory is transformed into a set of partial-differential equations. These equations only involve occupied Kohn-Sham orbitals and orbital shifts resulting from the difference between the exchange-correlation potential and the orbital-dependent potential. Due to the success of an analog scheme in the static case, a scheme that propagates orbitals and orbital shifts in real time is a natural candidate for an exact solution of the TDOEP equation. We investigate the numerical stability of such a scheme. An approximation beyond the Krieger-Li-Iafrate approximation for the time-dependent exchange-correlation potential ismore » analyzed.« less

Polarity effects and apparent ion recombination in microionization chambers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Jessica R., E-mail: miller@humonc.wisc.edu; Hooten, Brian D.; Micka, John A.

Purpose: Microchambers demonstrate anomalous voltage-dependent polarity effects. Existing polarity and ion recombination correction factors do not account for these effects. As a result, many commercial microchamber models do not meet the specification of a reference-class ionization chamber as defined by the American Association of Physicists in Medicine. The purpose of this investigation is to determine the cause of these voltage-dependent polarity effects. Methods: A series of microchamber prototypes were produced to isolate the source of the voltage-dependent polarity effects. Parameters including ionization-chamber collecting-volume size, stem and cable irradiation, chamber assembly, contaminants, high-Z materials, and individual chamber components were investigated. Measurementsmore » were performed with electrodes coated with graphite to isolate electrode conductivity. Chamber response was measured as the potential bias of the guard electrode was altered with respect to the collecting electrode, through the integration of additional power supplies. Ionization chamber models were also simulated using COMSOL Multiphysics software to investigate the effect of a potential difference between electrodes on electric field lines and collecting volume definition. Results: Investigations with microchamber prototypes demonstrated that the significant source of the voltage-dependent polarity effects was a potential difference between the guard and collecting electrodes of the chambers. The voltage-dependent polarity effects for each prototype were primarily isolated to either the guard or collecting electrode. Polarity effects were reduced by coating the isolated electrode with a conductive layer of graphite. Polarity effects were increased by introducing a potential difference between the electrodes. COMSOL simulations further demonstrated that for a given potential difference between electrodes, the collecting volume of the chamber changed as the applied voltage was altered, producing voltage-dependent polarity effects in the chamber response. Ionization chamber measurements and COMSOL simulations demonstrated an inverse relationship between the chamber collecting volume size and the severity of voltage-dependent polarity effects on chamber response. The effect of a given potential difference on chamber polarity effects was roughly ten times greater for microchambers as compared to Farmer-type chambers. Stem and cable irradiations, chamber assembly, contaminants, and high-Z materials were not found to be a significant source of the voltage-dependent polarity effects. Conclusions: A potential difference between the guard and collecting electrodes was found to be the primary source of the voltage-dependent polarity effects demonstrated by microchambers. For a given potential difference between electrodes, the relative change in the collecting volume is smaller for larger-volume chambers, illustrating why these polarity effects are not seen in larger-volume chambers with similar guard and collecting electrode designs. Thus, for small-volume chambers, it is necessary to reduce the potential difference between the guard and collecting electrodes in order to reduce polarity effects for reference dosimetry measurements.« less

Impairment of Coronary Arteriolar Endothelium-Dependent Dilation after Multi-Walled Carbon Nanotube Inhalation: A Time-Course Study

PubMed Central

Stapleton, Phoebe A.; Minarchick, Valerie C.; Cumpston, Amy M.; McKinney, Walter; Chen, Bean T.; Sager, Tina M.; Frazer, David G.; Mercer, Robert R.; Scabilloni, James; Andrew, Michael E.; Castranova, Vincent; Nurkiewicz, Timothy R.

2012-01-01

Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course of vascular alterations. Rats were exposed to MWCNT aerosols producing pulmonary deposition. Pulmonary inflammation via bronchoalveolar lavage and MWCNT translocation from the lungs to systemic organs was evident 24 h post-inhalation. Coronary arterioles were evaluated 24–168 h post-exposure to determine microvascular response to changes in transmural pressure, endothelium-dependent and -independent reactivity. Myogenic responsiveness, vascular smooth muscle reactivity to nitric oxide, and α-adrenergic responses all remained intact. However, a severe impact on endothelium-dependent dilation was observed within 24 h after MWCNT inhalation, a condition which improved, but did not fully return to control after 168 h. In conclusion, results indicate that MWCNT inhalation not only leads to pulmonary inflammation and cytotoxicity at low lung burdens, but also a low level of particle translocation to systemic organs. MWCNT inhalation also leads to impairments of endothelium-dependent dilation in the coronary microcirculation within 24 h, a condition which does not fully dissipate within 168 h. The innovations within the field of nanotechnology, while exciting and novel, can only reach their full potential if toxicity is first properly assessed. PMID:23203034

Host-dependent variables: The missing link to personalized medicine.

PubMed

Demlova, Regina; Zdrazilova-Dubska, Lenka; Sterba, Jaroslav; Stanta, Giorgio; Valik, Dalibor

2018-04-26

Individualized medicine has the potential to tailor anticancer therapy with the best response and highest safety margin to provide better patient care. However, modern targeted therapies are still being tested through clinical trials comparing preselected patient cohorts and assessed upon behaviour of group averages. Clinically manifesting malignant disease requires identification of host- and tumour-dependent variables such as biological characteristics of the tumour and its microenvironment including immune response features, and overall capacity of the host to receive, tolerate and efficiently utilize treatment. Contemporary medical oncology including clinical trial design need to refocus from assessing group averages to individuality taking into consideration time dependent host-associated characteristics and reinventing outliers to be appreciated as naturally occurring variables collectively determining the ultimate outcome of malignant disease. Copyright © 2018. Published by Elsevier Ltd.

Self-potential response to periodic pumping test: a numerical study

NASA Astrophysics Data System (ADS)

Konosavsky, Pavel; Maineult, Alexis; Narbut, Mikhail; Titov, Konstantin

2017-09-01

We numerically model self-potential responses associated with periodic pumping test experiments by sequential calculation of the hydraulic response and the coupled electrical potential. We assume the pumping test experiments with a fully saturated confined aquifer. Application of different excitation functions leads to quasi-linear trends in electrical records whose direction and intensity depend on the form of the excitation function. The hydraulic response is phase shifted compared to the excitation function; the phase shift increases quasi-linearly with the distance from the pumping well. For the electrical signals, we investigated separately the cases of conducting and insulating casings of the pumping well. For the conducting casing the electrical signals are larger in magnitude than that for the insulating casing; they reproduce the drawdown signals in the pumping well at any distance from the well and exhibit any phase shift with the increased distance. For the insulating casing, the electrical signals are phase shifted and their shape depends on the distance from the pumping well. Three characteristic regimes were found for the phase shift, φ, with the increased distance and for various hydraulic diffusivity values. At small distances φ increases quasi-linearly; at intermediate distances φ attends the value of π/2 and stay about this value (for relatively small diffusivity values); and at large distances φ attends the value of π and, stay about this value at larger distances. This behaviour of the electrical signals can be explained by two electrical sources of reverse polarity. They are (i) linear, time independent, and located at the pumping interval of the well; and (ii) volumetric, time dependent, with maximum value located in the aquifer at the distance corresponding to maximum variation of the hydraulic head magnitude with time. We also model the variation of the amplitude and phase of the hydraulic and electrical signals with increased excitation function period, and we show the characteristic periods corresponding to transition of the periodic pumping test regime to the classical pumping test regime, when the excitation function is considered as the step-function. This transition depends on the distance from the pumping well and the hydraulic diffusivity value of aquifer. Finally, with this modelling of saturated flow we reproduced in sufficient details the field data previously obtained by Maineult et al.

On the time-dependent Aharonov-Bohm effect

NASA Astrophysics Data System (ADS)

Jing, Jian; Zhang, Yu-Fei; Wang, Kang; Long, Zheng-Wen; Dong, Shi-Hai

2017-11-01

The Aharonov-Bohm effect in the background of a time-dependent vector potential is re-examined for both non-relativistic and relativistic cases. Based on the solutions to the Schrodinger and Dirac equations which contain the time-dependent magnetic vector potential, we find that contrary to the conclusions in a recent paper (Singleton and Vagenas 2013 [4]), the interference pattern will be altered with respect to time because of the time-dependent vector potential.

M-currents and other potassium currents in bullfrog sympathetic neurones

PubMed Central

Adams, P. R.; Brown, D. A.; Constanti, A.

1982-01-01

1. Bullfrog lumbar sympathetic neurones were voltage-clamped in vitro through twin micro-electrodes. Four different outward (K+) currents could be identified: (i) a large sustained voltage-sensitive delayed rectifier current (IK) activated at membrane potentials more positive than -25 mV; (ii) a calcium-dependent sustained outward current (IC) activated at similar positive potentials and peaking at +20 to +60 mV; (iii) a transient current (IA) activated at membrane potentials more positive than -60 mV after a hyperpolarizing pre-pulse, but which was rapidly and totally inactivated at all potentials within its activation range; and (iv) a new K+ current, the M-current (IM). 2. IM was detected as a non-inactivating current with a threshold at -60 mV. The underlying conductance GM showed a sigmoidal activation curve between -60 and -10 mV, with half-activation at -35 mV and a maximal value (ḠM) of 84±14 (S.E.M.) nS per neurone. The voltage sensitivity of GM could be expressed in terms of a simple Boltzmann distribution for a single multivalent gating particle. 3. IM activated and de-activated along an exponential time course with a time constant uniquely dependent upon voltage, maximizing at ≃ 150 ms at -35 mV at 22 °C. 4. Instantaneous current—voltage (I/V) curves were approximately linear in the presence of IM, suggesting that the M-channels do not show appreciable rectification. However, the time- and voltage-dependent opening of the M-channels induced considerable rectification in the steady-state I/V curves recorded under both voltage-clamp and current-clamp modes between -60 and -25 mV. Both time- and voltage-dependent rectification in the voltage responses to current injection over this range could be predicted from the kinetic properties of IM. 5. It is suggested that IM exerts a strong potential-clamping effect on the behaviour of these neurones at membrane potentials subthreshold to excitation. PMID:6294290

Pulse Responses of the Conducting Polymer Poly(3,4-ethylenedioxythiophene): Poly(styrenesulfonate)-Based Junctions

NASA Astrophysics Data System (ADS)

Zeng, Fei; Li, Xiaojun; Li, Sizhao; Chang, Chiating; Hu, Yuandong

2017-03-01

Pulse responses were studied for the heterojunctions within the structure of Ti/poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS)/Ti. The pulse response was found to resemble that of the action potential after the pulse width was modulated to a time scale of nanoseconds. Using the pulse as a stimulation protocol to simulate synaptic plasticity produced spike rate-dependent plasticity-like phenomena. Thus, the application scope of this conducting polymer-based memristor can be extended from a time scale of milliseconds to one of nanoseconds, depending on the requirement of neuromorphic circuits. Current oscillations were observed with a period within 100 ns. The mechanisms of the behavior response were analyzed according to memristor protocol. An interface barrier is thought to primarily account for the origin of the capacitive feature and the charge q, i.e., one of the basic characteristic of the memristor. The chain structure of this conducting polymer should primarily account for the origin of its inductive feature and the flux φ, i.e., another basic characteristic of the memristor.

Impacts of environmental variability on desiccation rate, plastic responses and population dynamics of Glossina pallidipes.

PubMed

Kleynhans, E; Clusella-Trullas, S; Terblanche, J S

2014-02-01

Physiological responses to transient conditions may result in costly responses with little fitness benefits, and therefore, a trade-off must exist between the speed of response and the duration of exposure to new conditions. Here, using the puparia of an important insect disease vector, Glossina pallidipes, we examine this potential trade-off using a novel combination of an experimental approach and a population dynamics model. Specifically, we explore and dissect the interactions between plastic physiological responses, treatment-duration and -intensity using an experimental approach. We then integrate these experimental results from organismal water-balance data and their plastic responses into a population dynamics model to examine the potential relative fitness effects of simulated transient weather conditions on population growth rates. The results show evidence for the predicted trade-off for plasticity of water loss rate (WLR) and the duration of new environmental conditions. When altered environmental conditions lasted for longer durations, physiological responses could match the new environmental conditions, and this resulted in a lower WLR and lower rates of population decline. At shorter time-scales however, a mismatch between acclimation duration and physiological responses was reflected by reduced overall population growth rates. This may indicate a potential fitness cost due to insufficient time for physiological adjustments to take place. The outcomes of this work therefore suggest plastic water balance responses have both costs and benefits, and these depend on the time-scale and magnitude of variation in environmental conditions. These results are significant for understanding the evolution of plastic physiological responses and changes in population abundance in the context of environmental variability. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Excited-state absorption in tetrapyridyl porphyrins: comparing real-time and quadratic-response time-dependent density functional theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowman, David N.; Asher, Jason C.; Fischer, Sean A.

2017-01-01

Threemeso-substituted tetrapyridyl porphyrins (free base, Ni(ii), and Cu(ii)) were investigated for their optical limiting (OL) capabilities using real-time (RT-), linear-response (LR-), and quadratic-response (QR-) time-dependent density functional theory (TDDFT) methods.

Response moderation models for conditional dependence between response time and response accuracy.

PubMed

Bolsinova, Maria; Tijmstra, Jesper; Molenaar, Dylan

2017-05-01

It is becoming more feasible and common to register response times in the application of psychometric tests. Researchers thus have the opportunity to jointly model response accuracy and response time, which provides users with more relevant information. The most common choice is to use the hierarchical model (van der Linden, 2007, Psychometrika, 72, 287), which assumes conditional independence between response time and accuracy, given a person's speed and ability. However, this assumption may be violated in practice if, for example, persons vary their speed or differ in their response strategies, leading to conditional dependence between response time and accuracy and confounding measurement. We propose six nested hierarchical models for response time and accuracy that allow for conditional dependence, and discuss their relationship to existing models. Unlike existing approaches, the proposed hierarchical models allow for various forms of conditional dependence in the model and allow the effect of continuous residual response time on response accuracy to be item-specific, person-specific, or both. Estimation procedures for the models are proposed, as well as two information criteria that can be used for model selection. Parameter recovery and usefulness of the information criteria are investigated using simulation, indicating that the procedure works well and is likely to select the appropriate model. Two empirical applications are discussed to illustrate the different types of conditional dependence that may occur in practice and how these can be captured using the proposed hierarchical models. © 2016 The British Psychological Society.

Time-dependent expression of hypertonic effects on bullfrog taste nerve responses to salts and bitter substances.

PubMed

Mashiyama, Kazunori; Nozawa, Yuhei; Ohtubo, Yoshitaka; Kumazawa, Takashi; Yoshii, Kiyonori

2014-03-27

We previously showed that the hypertonicity of taste stimulating solutions modified tonic responses, the quasi-steady state component following the transient (phasic) component of each integrated taste nerve response. Here we show that the hypertonicity opens tight junctions surrounding taste receptor cells in a time-dependent manner and modifies whole taste nerve responses in bullfrogs. We increased the tonicity of stimulating solutions with non-taste substances such as urea or ethylene glycol. The hypertonicity enhanced phasic responses to NaCl>0.2M, and suppressed those to NaCl<0.1M, 1mM CaCl2, and 1mM bitter substances (quinine, denatonium and strychnine). The hypertonicity also enhanced the phasic responses to a variety of 0.5M salts such as LiCl and KCl. The enhancing effect was increased by increasing the difference between the ionic mobilities of the cations and anions in the salt. A preincubation time >20s in the presence of 1M non-taste substances was needed to elicit both the enhancing and suppressing effects. Lucifer Yellow CH, a paracellular marker dye, diffused into bullfrog taste receptor organs in 30s in the presence of hypertonicity. These results agreed with our proposed mechanism of hypertonic effects that considered the diffusion potential across open tight junctions. Copyright © 2014 Elsevier B.V. All rights reserved.

Harmonic generation by yeast cells in response to low-frequency electric fields

NASA Astrophysics Data System (ADS)

Nawarathna, D.; Claycomb, J. R.; Cardenas, G.; Gardner, J.; Warmflash, D.; Miller, J. H., Jr.; Widger, W. R.

2006-05-01

We report on harmonic generation by budding yeast cells (Saccharomyces cerevisiae, 108cells/ml ) in response to sinusoidal electric fields with amplitudes ranging from zero to 5V/cm in the frequency range 10-300Hz . The cell-generated harmonics are found to exhibit strong amplitude and frequency dependence. Sodium metavanadate, an inhibitor of the proton pump known as H+ -ATPase, and glucose, a substrate of H+ -ATPase, are found to increase harmonic production at low amplitudes while reducing it at large amplitudes. This P-type proton pump can be driven by an oscillatory transmembrane potential, and its nonlinear response is believed to be largely responsible for harmonic production at low frequencies in yeast cells. We find that the observed harmonics show dramatic changes with time and in their field and frequency dependence after perturbing the system by adding an inhibitor, substrate, or membrane depolarizer to the cell suspension.

Suppression of Proinflammatory Cytokines in Functionalized Fullerene-Exposed Dermal Keratinocytes

DOE PAGES

Gao, Jun; Wang, Hsing-Lin; Iyer, Rashi

2010-01-01

Initial experiments using differentially functionalized fullerenes, CD-, hexa-, and tris-, suggested a properties dependent effect on cytotoxic and proliferative responses in human skin keratinocytes. In the present study we investigated the cytokine secretion profile of dermal epithelial cells exposed to functionalized fullerenes. Keratinocyte-derived cytokines affect homing and trafficking of normal and malignant epidermal immune as well as nonimmune cells in vivo. These cytokines are critical for regulating activation, proliferation, and differentiation of epidermal cells. Our results indicate that tris- (size range <100 nm) significantly reduces inflammatory cytokine release in a dose- and time-dependent manner. In contrast CD- demonstrated a relatively pro-inflammatorymore » cytokine response, while hexa- did not significantly perturb cytokine responses. Physical and chemical characterizations of these engineered nanomaterials suggest that the disparate biological responses observed may potentially be a function of the aggregation properties of these fullerenes.« less

Delayed and Temporally Imprecise Neurotransmission in Reorganizing Cortical Microcircuits

PubMed Central

Barnes, Samuel J.; Cheetham, Claire E.; Liu, Yan; Bennett, Sophie H.; Albieri, Giorgia; Jorstad, Anne A.; Knott, Graham W.

2015-01-01

Synaptic neurotransmission is modified at cortical connections throughout life. Varying the amplitude of the postsynaptic response is one mechanism that generates flexible signaling in neural circuits. The timing of the synaptic response may also play a role. Here, we investigated whether weakening and loss of an entire connection between excitatory cortical neurons was foreshadowed in the timing of the postsynaptic response. We made electrophysiological recordings in rat primary somatosensory cortex that was undergoing experience-dependent loss of complete local excitatory connections. The synaptic latency of pyramid–pyramid connections, which typically comprise multiple synapses, was longer and more variable. Connection strength and latency were not correlated. Instead, prolonged latency was more closely related to progression of connection loss. The action potential waveform and axonal conduction velocity were unaffected, suggesting that the altered timing of neurotransmission was attributable to a synaptic mechanism. Modeling studies indicated that increasing the latency and jitter at a subset of synapses reduced the number of action potentials fired by a postsynaptic neuron. We propose that prolonged synaptic latency and diminished temporal precision of neurotransmission are hallmarks of impending loss of a cortical connection. PMID:26085628

Constitutive Theory Developed for Monolithic Ceramic Materials

NASA Technical Reports Server (NTRS)

Janosik, Lesley A.

1998-01-01

With the increasing use of advanced ceramic materials in high-temperature structural applications such as advanced heat engine components, the need arises to accurately predict thermomechanical behavior that is inherently time-dependent and that is hereditary in the sense that the current behavior depends not only on current conditions but also on the material's thermomechanical history. Most current analytical life prediction methods for both subcritical crack growth and creep models use elastic stress fields to predict the time-dependent reliability response of components subjected to elevated service temperatures. Inelastic response at high temperatures has been well documented in the materials science literature for these material systems, but this issue has been ignored by the engineering design community. From a design engineer's perspective, it is imperative to emphasize that accurate predictions of time-dependent reliability demand accurate stress field information. Ceramic materials exhibit different time-dependent behavior in tension and compression. Thus, inelastic deformation models for ceramics must be constructed in a fashion that admits both sensitivity to hydrostatic stress and differing behavior in tension and compression. A number of constitutive theories for materials that exhibit sensitivity to the hydrostatic component of stress have been proposed that characterize deformation using time-independent classical plasticity as a foundation. However, none of these theories allow different behavior in tension and compression. In addition, these theories are somewhat lacking in that they are unable to capture the creep, relaxation, and rate-sensitive phenomena exhibited by ceramic materials at high temperatures. The objective of this effort at the NASA Lewis Research Center has been to formulate a macroscopic continuum theory that captures these time-dependent phenomena. Specifically, the effort has focused on inelastic deformation behavior associated with these service conditions by developing a multiaxial viscoplastic constitutive model that accounts for time-dependent hereditary material deformation (such as creep and stress relaxation) in monolithic structural ceramics. Using continuum principles of engineering mechanics, we derived the complete viscoplastic theory from a scalar dissipative potential function.

Dose Response of Endotoxin on Hepatocyte and Muscle Mitochondrial Respiration In Vitro

PubMed Central

Brandt, Sebastian; Porta, Francesca; Jakob, Stephan M.; Takala, Jukka; Djafarzadeh, Siamak

2015-01-01

Introduction. Results on mitochondrial dysfunction in sepsis are controversial. We aimed to assess effects of LPS at wide dose and time ranges on hepatocytes and isolated skeletal muscle mitochondria. Methods. Human hepatocellular carcinoma cells (HepG2) were exposed to placebo or LPS (0.1, 1, and 10 μg/mL) for 4, 8, 16, and 24 hours and primary human hepatocytes to 1 μg/mL LPS or placebo (4, 8, and 16 hours). Mitochondria from porcine skeletal muscle samples were exposed to increasing doses of LPS (0.1–100 μg/mg) for 2 and 4 hours. Respiration rates of intact and permeabilized cells and isolated mitochondria were measured by high-resolution respirometry. Results. In HepG2 cells, LPS reduced mitochondrial membrane potential and cellular ATP content but did not modify basal respiration. Stimulated complex II respiration was reduced time-dependently using 1 μg/mL LPS. In primary human hepatocytes, stimulated mitochondrial complex II respiration was reduced time-dependently using 1 μg/mL LPS. In isolated porcine skeletal muscle mitochondria, stimulated respiration decreased at high doses (50 and 100 μg/mL LPS). Conclusion. LPS reduced cellular ATP content of HepG2 cells, most likely as a result of the induced decrease in membrane potential. LPS decreased cellular and isolated mitochondrial respiration in a time-dependent, dose-dependent and complex-dependent manner. PMID:25649304

Spinning Reserve from Responsive Load

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kueck, John D; Kirby, Brendan J; Laughner, T

2009-01-01

As power system costs rise and capacity is strained demand response can provide a significant system reliability benefit at a potentially attractive cost. The 162 room Music Road Hotel in Pigeon Forge Tennessee agreed to host a spinning reserve test. The Tennessee Valley Authority (TVA) supplied real-time metering and monitoring expertise to record total hotel load during both normal operations and testing. Preliminary testing showed that hotel load can be curtailed by 22% to 37% depending on the outdoor temperature and the time of day. The load drop was very rapid, essentially as fast as the 2 second metering couldmore » detect.« less

Spike-timing-dependent plasticity in the human dorso-lateral prefrontal cortex.

PubMed

Casula, Elias Paolo; Pellicciari, Maria Concetta; Picazio, Silvia; Caltagirone, Carlo; Koch, Giacomo

2016-12-01

Changes in the synaptic strength of neural connections are induced by repeated coupling of activity of interconnected neurons with precise timing, a phenomenon known as spike-timing-dependent plasticity (STDP). It is debated if this mechanism exists in large-scale cortical networks in humans. We combined transcranial magnetic stimulation (TMS) with concurrent electroencephalography (EEG) to directly investigate the effects of two paired associative stimulation (PAS) protocols (fronto-parietal and parieto-frontal) of pre and post-synaptic inputs within the human fronto-parietal network. We found evidence that the dorsolateral prefrontal cortex (DLPFC) has the potential to form robust STDP. Long-term potentiation/depression of TMS-evoked cortical activity is prompted after that DLPFC stimulation is followed/preceded by posterior parietal stimulation. Such bidirectional changes are paralleled by sustained increase/decrease of high-frequency oscillatory activity, likely reflecting STDP responsivity. The current findings could be important to drive plasticity of damaged cortical circuits in patients with cognitive or psychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

The electrical response of turtle cones to flashes and steps of light.

PubMed

Baylor, D A; Hodgkin, A L; Lamb, T D

1974-11-01

1. The linear response of turtle cones to weak flashes or steps of light was usually well fitted by equations based on a chain of six or seven reactions with time constants varying over about a 6-fold range.2. The temperature coefficient (Q(10)) of the reciprocal of the time to peak of the response to a flash was 1.8 (15-25 degrees C), corresponding to an activation energy of 10 kcal/mole.3. Electrical measurements with one internal electrode and a balancing circuit gave the following results on red-sensitive cones of high resistance: resistance across cell surface in dark 50-170 MOmega; time constant in dark 4-6.5 msec. The effect of a bright light was to increase the resistance and time constant by 10-30%.4. If the cell time constant, resting potential and maximum hyperpolarization are known, the fraction of ionic channels blocked by light at any instant can be calculated from the hyperpolarization and its rate of change. At times less than 50 msec the shape of this relation is consistent with the idea that the concentration of a blocking molecule which varies linearly with light intensity is in equilibrium with the fraction of ionic channels blocked.5. The rising phase of the response to flashes and steps of light covering a 10(5)-fold range of intensities is well fitted by a theory in which the essential assumptions are that (i) light starts a linear chain of reactions leading to the production of a substance which blocks ionic channels in the outer segment, (ii) an equilibrium between the blocking molecules and unblocked channels is established rapidly, and (iii) the electrical properties of the cell can be represented by a simple circuit with a time constant in the dark of about 6 msec.6. Deviations from the simple theory which occur after 50 msec are attributed partly to a time-dependent desensitization mechanism and partly to a change in saturation potential resulting from a voltage-dependent change in conductance.7. The existence of several components in the relaxation of the potential to its resting level can be explained by supposing that the ;substance' which blocks light sensitive ionic channels is inactivated in a series of steps.

Neuromodulated Spike-Timing-Dependent Plasticity, and Theory of Three-Factor Learning Rules.

PubMed

Frémaux, Nicolas; Gerstner, Wulfram

2015-01-01

Classical Hebbian learning puts the emphasis on joint pre- and postsynaptic activity, but neglects the potential role of neuromodulators. Since neuromodulators convey information about novelty or reward, the influence of neuromodulators on synaptic plasticity is useful not just for action learning in classical conditioning, but also to decide "when" to create new memories in response to a flow of sensory stimuli. In this review, we focus on timing requirements for pre- and postsynaptic activity in conjunction with one or several phasic neuromodulatory signals. While the emphasis of the text is on conceptual models and mathematical theories, we also discuss some experimental evidence for neuromodulation of Spike-Timing-Dependent Plasticity. We highlight the importance of synaptic mechanisms in bridging the temporal gap between sensory stimulation and neuromodulatory signals, and develop a framework for a class of neo-Hebbian three-factor learning rules that depend on presynaptic activity, postsynaptic variables as well as the influence of neuromodulators.

Does Employer-Provided Health Insurance Constrain Labor Supply Adjustments to Health Shocks? New Evidence on Women Diagnosed with Breast Cancer

PubMed Central

Neumark, David; Barkowski, Scott

2013-01-01

Employment-contingent health insurance may create incentives for ill workers to remain employed at a sufficient level (usually full-time) to maintain access to health insurance coverage. We study employed married women, comparing the labor supply responses to new breast cancer diagnoses of women dependent on their own employment for health insurance with the responses of women who are less dependent on their own employment for health insurance, because of actual or potential access to health insurance through their spouse’s employer. We find evidence that women who depend on their own job for health insurance reduce their labor supply by less after a diagnosis of breast cancer. In the estimates that best control for unobservables associated with health insurance status, the hours reduction for women who continue to work is 8 to 11 percent smaller. Women’s subjective responses to questions about working more to maintain health insurance are consistent with the conclusions from observed behavior. PMID:23891911

Plug-and-Play Multicellular Circuits with Time-Dependent Dynamic Responses.

PubMed

Urrios, Arturo; Gonzalez-Flo, Eva; Canadell, David; de Nadal, Eulàlia; Macia, Javier; Posas, Francesc

2018-04-20

Synthetic biology studies aim to develop cellular devices for biomedical applications. These devices, based on living instead of electronic or electromechanic technology, might provide alternative treatments for a wide range of diseases. However, the feasibility of these devices depends, in many cases, on complex genetic circuits that must fulfill physiological requirements. In this work, we explored the potential of multicellular architectures to act as an alternative to complex circuits for implementation of new devices. As a proof of concept, we developed specific circuits for insulin or glucagon production in response to different glucose levels. Here, we show that fundamental features, such as circuit's affinity or sensitivity, are dependent on the specific configuration of the multicellular consortia, providing a method for tuning these properties without genetic engineering. As an example, we have designed and built circuits with an incoherent feed-forward loop architecture (FFL) that can be easily adjusted to generate single pulse responses. Our results might serve as a blueprint for future development of cellular devices for glycemia regulation in diabetic patients.

Nonequilibrium quantum solvation with a time-dependent Onsager cavity

NASA Astrophysics Data System (ADS)

Kirchberg, H.; Nalbach, P.; Thorwart, M.

2018-04-01

We formulate a theory of nonequilibrium quantum solvation in which parameters of the solvent are explicitly depending on time. We assume in a simplest approach a spherical molecular Onsager cavity with a time-dependent radius. We analyze the relaxation properties of a test molecular point dipole in a dielectric solvent and consider two cases: (i) a shrinking Onsager sphere and (ii) a breathing Onsager sphere. Due to the time-dependent solvent, the frequency-dependent response function of the dipole becomes time-dependent. For a shrinking Onsager sphere, the dipole relaxation is in general enhanced. This is reflected in a temporally increasing linewidth of the absorptive part of the response. Furthermore, the effective frequency-dependent response function shows two peaks in the absorptive part which are symmetrically shifted around the eigenfrequency. By contrast, a breathing sphere reduces damping as compared to the static sphere. Interestingly, we find a non-monotonous dependence of the relaxation rate on the breathing rate and a resonant suppression of damping when both rates are comparable. Moreover, the linewidth of the absorptive part of the response function is strongly reduced for times when the breathing sphere reaches its maximal extension.

Nonequilibrium quantum solvation with a time-dependent Onsager cavity.

PubMed

Kirchberg, H; Nalbach, P; Thorwart, M

2018-04-28

We formulate a theory of nonequilibrium quantum solvation in which parameters of the solvent are explicitly depending on time. We assume in a simplest approach a spherical molecular Onsager cavity with a time-dependent radius. We analyze the relaxation properties of a test molecular point dipole in a dielectric solvent and consider two cases: (i) a shrinking Onsager sphere and (ii) a breathing Onsager sphere. Due to the time-dependent solvent, the frequency-dependent response function of the dipole becomes time-dependent. For a shrinking Onsager sphere, the dipole relaxation is in general enhanced. This is reflected in a temporally increasing linewidth of the absorptive part of the response. Furthermore, the effective frequency-dependent response function shows two peaks in the absorptive part which are symmetrically shifted around the eigenfrequency. By contrast, a breathing sphere reduces damping as compared to the static sphere. Interestingly, we find a non-monotonous dependence of the relaxation rate on the breathing rate and a resonant suppression of damping when both rates are comparable. Moreover, the linewidth of the absorptive part of the response function is strongly reduced for times when the breathing sphere reaches its maximal extension.

Motherhood and drug-dependency: the attributes of full-time versus part-time responsibility for child care.

PubMed

Jackson, M R; Berry, G L

1994-10-01

This study examined differences between the maternal characteristics of African-American drug-dependent mothers who have full-time responsibility for child care and those having part-time responsibility. The study revealed that full-time mothers have significantly higher levels of maternal adaptation than part-time mothers. For part-time mothers, the level of maternal adaptation or self-esteem did not fluctuate, regardless of whether she saw the child 4 days a week or once a month. The article identifies variables that may facilitate better maternal behaviors among drug-dependent mothers.

Surface chemistry of gold nanoparticles determines the biocorona composition impacting cellular uptake, toxicity and gene expression profiles in human endothelial cells.

PubMed

Chandran, Parwathy; Riviere, Jim E; Monteiro-Riviere, Nancy A

2017-05-01

This study investigated the role of nanoparticle size and surface chemistry on biocorona composition and its effect on uptake, toxicity and cellular responses in human umbilical vein endothelial cells (HUVEC), employing 40 and 80 nm gold nanoparticles (AuNP) with branched polyethyleneimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG) coatings. Proteomic analysis identified 59 hard corona proteins among the various AuNP, revealing largely surface chemistry-dependent signature adsorbomes exhibiting human serum albumin (HSA) abundance. Size distribution analysis revealed the relative instability and aggregation inducing potential of bare and corona-bound BPEI-AuNP, over LA- and PEG-AuNP. Circular dichroism analysis showed surface chemistry-dependent conformational changes of proteins binding to AuNP. Time-dependent uptake of bare, plasma corona (PC) and HSA corona-bound AuNP (HSA-AuNP) showed significant reduction in uptake with PC formation. Cell viability studies demonstrated dose-dependent toxicity of BPEI-AuNP. Transcriptional profiling studies revealed 126 genes, from 13 biological pathways, to be differentially regulated by 40 nm bare and PC-bound BPEI-AuNP (PC-BPEI-AuNP). Furthermore, PC formation relieved the toxicity of cationic BPEI-AuNP by modulating expression of genes involved in DNA damage and repair, heat shock response, mitochondrial energy metabolism, oxidative stress and antioxidant response, and ER stress and unfolded protein response cascades, which were aberrantly expressed in bare BPEI-AuNP-treated cells. NP surface chemistry is shown to play the dominant role over size in determining the biocorona composition, which in turn modulates cell uptake, and biological responses, consequently defining the potential safety and efficacy of nanoformulations.

Emotion self-regulation and empathy depend upon longer stimulus exposure.

PubMed

Ikezawa, Satoru; Corbera, Silvia; Wexler, Bruce E

2014-10-01

Observation of others in pain induces positive elevation (pain effect) in late event-related potentials (ERP). This effect is associated with top-down attention regulating processes. It has previously been shown that stimulus exposure duration can affect top-down attentional modulation of response to threat-related stimuli. We investigated the effect of exposure duration on ERP response to others in pain. Two late ERP components, P3 and late positive potentials (LPP), from 18 healthy people were measured while they viewed pictures of hands in painful or neutral situations for either 200 or 500 ms, during two task conditions (pain judgment and counting hands). P3 and LPP pain effects during the pain judgment condition were significantly greater with 500 ms than 200 ms stimulus presentation. Ours is the first study to suggest that engagement of empathy-related self-regulatory processes reflected in late potentials requires longer exposure to the pain-related stimulus. Although this is important information about the relationship between early sensory and subsequent brain processing, and about engagement of self-regulatory processes, the neural basis of this time-dependence remains unclear. It might be important to investigate the relationship between stimulus duration and empathic response in clinical populations where issues of self-regulation, empathic response and speed of information processing exist. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Global and Regional Temperature-change Potentials for Near-term Climate Forcers

NASA Technical Reports Server (NTRS)

Collins, W.J.; Fry, M.M.; Yu, H.; Fuglestvedt, J. S.; Shindell, D. T.; West, J. J.

2013-01-01

We examine the climate effects of the emissions of near-term climate forcers (NTCFs) from 4 continental regions (East Asia, Europe, North America and South Asia) using results from the Task Force on Hemispheric Transport of Air Pollution Source-Receptor global chemical transport model simulations. We address 3 aerosol species (sulphate, particulate organic matter and black carbon) and 4 ozone precursors (methane, reactive nitrogen oxides (NOx), volatile organic compounds and carbon monoxide). We calculate the global climate metrics: global warming potentials (GWPs) and global temperature change potentials (GTPs). For the aerosols these metrics are simply time-dependent scalings of the equilibrium radiative forcings. The GTPs decrease more rapidly with time than the GWPs. The aerosol forcings and hence climate metrics have only a modest dependence on emission region. The metrics for ozone precursors include the effects on the methane lifetime. The impacts via methane are particularly important for the 20 yr GTPs. Emissions of NOx and VOCs from South Asia have GWPs and GTPs of higher magnitude than from the other Northern Hemisphere regions. The analysis is further extended by examining the temperature-change impacts in 4 latitude bands, and calculating absolute regional temperature-change potentials (ARTPs). The latitudinal pattern of the temperature response does not directly follow the pattern of the diagnosed radiative forcing. We find that temperatures in the Arctic latitudes appear to be particularly sensitive to BC emissions from South Asia. The northern mid-latitude temperature response to northern mid-latitude emissions is approximately twice as large as the global average response for aerosol emission, and about 20-30% larger than the global average for methane, VOC and CO emissions.

Spatialized audio improves call sign recognition during multi-aircraft control.

PubMed

Kim, Sungbin; Miller, Michael E; Rusnock, Christina F; Elshaw, John J

2018-07-01

We investigated the impact of a spatialized audio display on response time, workload, and accuracy while monitoring auditory information for relevance. The human ability to differentiate sound direction implies that spatial audio may be used to encode information. Therefore, it is hypothesized that spatial audio cues can be applied to aid differentiation of critical versus noncritical verbal auditory information. We used a human performance model and a laboratory study involving 24 participants to examine the effect of applying a notional, automated parser to present audio in a particular ear depending on information relevance. Operator workload and performance were assessed while subjects listened for and responded to relevant audio cues associated with critical information among additional noncritical information. Encoding relevance through spatial location in a spatial audio display system--as opposed to monophonic, binaural presentation--significantly reduced response time and workload, particularly for noncritical information. Future auditory displays employing spatial cues to indicate relevance have the potential to reduce workload and improve operator performance in similar task domains. Furthermore, these displays have the potential to reduce the dependence of workload and performance on the number of audio cues. Published by Elsevier Ltd.

Exploring time- and frequency- dependent functional connectivity and brain networks during deception with single-trial event-related potentials

NASA Astrophysics Data System (ADS)

Gao, Jun-Feng; Yang, Yong; Huang, Wen-Tao; Lin, Pan; Ge, Sheng; Zheng, Hong-Mei; Gu, Ling-Yun; Zhou, Hui; Li, Chen-Hong; Rao, Ni-Ni

2016-11-01

To better characterize the cognitive processes and mechanisms that are associated with deception, wavelet coherence was employed to evaluate functional connectivity between different brain regions. Two groups of subjects were evaluated for this purpose: 32 participants were required to either tell the truth or to lie when facing certain stimuli, and their electroencephalogram signals on 12 electrodes were recorded. The experimental results revealed that deceptive responses elicited greater connectivity strength than truthful responses, particularly in the θ band on specific electrode pairs primarily involving connections between the prefrontal/frontal and central regions and between the prefrontal/frontal and left parietal regions. These results indicate that these brain regions play an important role in executing lying responses. Additionally, three time- and frequency-dependent functional connectivity networks were proposed to thoroughly reflect the functional coupling of brain regions that occurs during lying. Furthermore, the wavelet coherence values for the connections shown in the networks were extracted as features for support vector machine training. High classification accuracy suggested that the proposed network effectively characterized differences in functional connectivity between the two groups of subjects over a specific time-frequency area and hence could be a sensitive measurement for identifying deception.

Charging in the ac Conductance of a Double Barrier Resonant Tunneling Structure

NASA Technical Reports Server (NTRS)

Anantram, M. P.; Saini, Subhash (Technical Monitor)

1998-01-01

There have been many studies of the linear response ac conductance of a double barrier resonant tunneling structure (DBRTS), both at zero and finite dc biases. While these studies are important, they fail to self consistently include the effect of the time dependent charge density in the well. In this paper, we calculate the ac conductance at both zero and finite do biases by including the effect of the time dependent charge density in the well in a self consistent manner. The charge density in the well contributes to both the flow of displacement currents in the contacts and the time dependent potential in the well. We find that including these effects can make a significant difference to the ac conductance and the total ac current is not equal to the simple average of the non-selfconsistently calculated conduction currents in the two contacts. This is illustrated by comparing the results obtained with and without the effect of the time dependent charge density included correctly. Some possible experimental scenarios to observe these effects are suggested.

A complex-polarization-propagator protocol for magneto-chiral axial dichroism and birefringence dispersion.

PubMed

Cukras, Janusz; Kauczor, Joanna; Norman, Patrick; Rizzo, Antonio; Rikken, Geert L J A; Coriani, Sonia

2016-05-21

A computational protocol for magneto-chiral dichroism and magneto-chiral birefringence dispersion is presented within the framework of damped response theory, also known as complex polarization propagator theory, at the level of time-dependent Hartree-Fock and time-dependent density functional theory. Magneto-chiral dichroism and magneto-chiral birefringence spectra in the (resonant) frequency region below the first ionization threshold of R-methyloxirane and l-alanine are presented and compared with the corresponding results obtained for both the electronic circular dichroism and the magnetic circular dichroism. The additional information content yielded by the magneto-chiral phenomena, as well as their potential experimental detectability for the selected species, is discussed.

Velocity-gauge real-time TDDFT within a numerical atomic orbital basis set

NASA Astrophysics Data System (ADS)

Pemmaraju, C. D.; Vila, F. D.; Kas, J. J.; Sato, S. A.; Rehr, J. J.; Yabana, K.; Prendergast, David

2018-05-01

The interaction of laser fields with solid-state systems can be modeled efficiently within the velocity-gauge formalism of real-time time dependent density functional theory (RT-TDDFT). In this article, we discuss the implementation of the velocity-gauge RT-TDDFT equations for electron dynamics within a linear combination of atomic orbitals (LCAO) basis set framework. Numerical results obtained from our LCAO implementation, for the electronic response of periodic systems to both weak and intense laser fields, are compared to those obtained from established real-space grid and Full-Potential Linearized Augmented Planewave approaches. Potential applications of the LCAO based scheme in the context of extreme ultra-violet and soft X-ray spectroscopies involving core-electronic excitations are discussed.

INTERPRETATION OF THE CANCER RESPONSE TO POTENTIAL RENTAL CARCINOGENS IN THE TSC2 KNOCKOUT (EKER) RAT IS DEPENDENT ON LENGTH OF TREATMENT.

EPA Science Inventory

INTERPRETATION OF THE CANCER RESPONSE TO POTENTIAL RENAL CARCINOGENS IN THE TSC2 KNOCKOUT (EKER) RAT IS DEPENDENT ON LENGTH OF TREATMENT.

Genetically increasing the function of oncogenes or knocking out the function of a tumor supressor gene has dramatically increased the...

A single-electron picture based on the multiconfiguration time-dependent Hartree-Fock method: application to the anisotropic ionization and subsequent high-harmonic generation of the CO molecule

NASA Astrophysics Data System (ADS)

Ohmura, S.; Kato, T.; Oyamada, T.; Koseki, S.; Ohmura, H.; Kono, H.

2018-02-01

The mechanisms of anisotropic near-IR tunnel ionization and high-order harmonic generation (HHG) in a CO molecule are theoretically investigated by using the multiconfiguration time-dependent Hartree-Fock (MCTDHF) method developed for the simulation of multielectron dynamics of molecules. The multielectron dynamics obtained by numerically solving the equations of motion (EOMs) in the MCTDHF method is converted to a single orbital picture in the natural orbital representation where the first-order reduced density matrix is diagonalized. The ionization through each natural orbital is examined and the process of HHG is classified into different optical paths designated by a combinations of initial, intermediate and final natural orbitals. The EOMs for natural spin-orbitals are also derived within the framework of the MCTDHF, which maintains the first-order reduced density matrix to be a diagonal one throughout the time propagation of a many-electron wave function. The orbital dependent, time-dependent effective potentials that govern the dynamics of respective time-dependent natural orbitals are deduced from the derived EOMs, of which the temporal variation can be used to interpret the motion of the electron density associated with each natural spin-orbital. The roles of the orbital shape, multiorbital ionization, linear Stark effect and multielectron interaction in the ionization and HHG of a CO molecule are revealed by the effective potentials obtained. When the laser electric field points to the nucleus O from C, tunnel ionization from the C atom side is enhanced; a hump structure originating from multielectron interaction is then formed on the top of the field-induced distorted barrier of the HOMO effective potential. This hump formation, responsible for the directional anisotropy of tunnel ionization, restrains the influence of the linear Stark effect on the energy shifts of bound states.

A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system

PubMed Central

2012-01-01

Background This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. Discussion The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. Summary Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine. PMID:23088629

A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system.

PubMed

Bell, Iris R; Koithan, Mary

2012-10-22

This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create "top-down" nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism's allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine.

Assessing frequency-dependent site polarisabilities in linear response polarisable embedding

NASA Astrophysics Data System (ADS)

Nørby, Morten S.; Vahtras, Olav; Norman, Patrick; Kongsted, Jacob

2017-01-01

In this paper, we discuss the impact of using a frequency-dependent embedding potential in quantum chemical embedding calculations of response properties. We show that the introduction of a frequency-dependent embedding potential leads to further model complications upon solving the central equations defining specific molecular properties. On the other hand, we also show from a numerical point of view that the consequences of using such a frequency-dependent embedding potential is almost negligible. Thus, for the kind of systems and processes studied in this paper the general recommendation is to use frequency-independent embedding potentials since this leads to less complicated model issues. However, larger effects are expected if the absorption bands of the environment are closer to that of the region treated using quantum mechanics.

Ultraviolet laser-induced lateral photovoltaic response in anisotropic black shale

NASA Astrophysics Data System (ADS)

Miao, Xinyang; Zhu, Jing; Zhao, Kun; Yue, Wenzheng

2017-12-01

The anisotropy of shale has significant impact on oil and gas exploration and engineering. In this paper, a-248 nm ultraviolet laser was employed to assess the anisotropic lateral photovoltaic (LPV) response of shale. Anisotropic angle-depending voltage signals were observed with different peak amplitudes ( V p) and decay times. We employed exponential models to explain the charge carrier transport in horizontal and vertical directions. Dependences of the laser-induced LPV on the laser spot position were observed. Owing to the Dember effect and the layered structure of shale, V p shows an approximately linear dependence with the laser-irradiated position for the 0° shale sample but nonlinearity for the 45° and 90° ones. The results demonstrate that the laser-induced voltage method is very sensitive to the structure of materials, and thus has a great potential in oil and gas reservoir characterization.

Temperature dependence of electrical properties of mixture of exogenous neurotransmitters dopamine and epinephrine

NASA Astrophysics Data System (ADS)

Patki, Mugdha; Patil, Vidya

2016-05-01

Neurotransmitters are chemical messengers that support the communication between the neurons. In vitro study of exogenous neurotransmitters Dopamine and Epinephrine and their mixture, carried out to learn about their electrical properties being dielectric constant and conductivity amongst others. Dielectric constant and conductivity of the selected neurotransmitters are found to increase with temperature. As a result, the time constant of the system increases with temperature. This change leads to increase in the time taken by the synapse to transport the action potential. The correlation between physical properties of exogenous neurotransmitters and psychological and physiological behaviour of human being may be understood with the help of current study. The response time of Epinephrine is in microseconds whereas response time of Dopamine is in milliseconds. The response time for both the neurotransmitters and their mixture is found to be increasing with temperature indicating the symptoms such as depression, apathy, chronic fatigue and low physical energy with no desire to exercise the body, which are observed during the fever.

Synaptic characteristics with strong analog potentiation, depression, and short-term to long-term memory transition in a Pt/CeO2/Pt crossbar array structure

NASA Astrophysics Data System (ADS)

Kim, Hyung Jun; Park, Daehoon; Yang, Paul; Beom, Keonwon; Kim, Min Ju; Shin, Chansun; Kang, Chi Jung; Yoon, Tae-Sik

2018-06-01

A crossbar array of Pt/CeO2/Pt memristors exhibited the synaptic characteristics such as analog, reversible, and strong resistance change with a ratio of ∼103, corresponding to wide dynamic range of synaptic weight modulation as potentiation and depression with respect to the voltage polarity. In addition, it presented timing-dependent responses such as paired-pulse facilitation and the short-term to long-term memory transition by increasing amplitude, width, and repetition number of voltage pulse and reducing the interval time between pulses. The memory loss with a time was fitted with a stretched exponential relaxation model, revealing the relation of memory stability with the input stimuli strength. The resistance change was further enhanced but its stability got worse as increasing measurement temperature, indicating that the resistance was changed as a result of voltage- and temperature-dependent electrical charging and discharging to alter the energy barrier for charge transport. These detailed synaptic characteristics demonstrated the potential of crossbar array of Pt/CeO2/Pt memristors as artificial synapses in highly connected neuron-synapse network.

Synaptic characteristics with strong analog potentiation, depression, and short-term to long-term memory transition in a Pt/CeO2/Pt crossbar array structure.

PubMed

Kim, Hyung Jun; Park, Daehoon; Yang, Paul; Beom, Keonwon; Kim, Min Ju; Shin, Chansun; Kang, Chi Jung; Yoon, Tae-Sik

2018-06-29

A crossbar array of Pt/CeO 2 /Pt memristors exhibited the synaptic characteristics such as analog, reversible, and strong resistance change with a ratio of ∼10 3 , corresponding to wide dynamic range of synaptic weight modulation as potentiation and depression with respect to the voltage polarity. In addition, it presented timing-dependent responses such as paired-pulse facilitation and the short-term to long-term memory transition by increasing amplitude, width, and repetition number of voltage pulse and reducing the interval time between pulses. The memory loss with a time was fitted with a stretched exponential relaxation model, revealing the relation of memory stability with the input stimuli strength. The resistance change was further enhanced but its stability got worse as increasing measurement temperature, indicating that the resistance was changed as a result of voltage- and temperature-dependent electrical charging and discharging to alter the energy barrier for charge transport. These detailed synaptic characteristics demonstrated the potential of crossbar array of Pt/CeO 2 /Pt memristors as artificial synapses in highly connected neuron-synapse network.

Structure and Dynamics of the Solar Corona

NASA Technical Reports Server (NTRS)

Schnack, D. D.

1994-01-01

Advanced computational techniques were used to study solar coronal heating and coronal mass ejections. A three dimensional, time dependent resistive magnetohydrodynamic code was used to study the dynamic response of a model corona to continuous, slow, random magnetic footpoint displacements in the photosphere. Three dimensional numerical simulations of the response of the corona to simple smooth braiding flows in the photosphere were calculated to illustrate and understand the spontaneous formation of current filaments. Two dimensional steady state helmet streamer configurations were obtained by determining the time asymptotic state of the interaction of an initially one dimensinal transponic solar wind with a spherical potential dipole field. The disruption of the steady state helmet streamer configuration was studied as a response to shearing of the magnetic footpoints of the closed field lines under the helmet.

Potentiation of lymphocyte proliferative responses by nickel sulfide

NASA Technical Reports Server (NTRS)

Jaramillo, A.; Sonnenfeld, G.

1992-01-01

Crystalline nickel sulfide (NiS) induced a spleen cell proliferation that resembles a mixed lymphocyte reaction (MLR). It depended on cell-cell interaction, induced high levels of interleukin-1 (IL-1) and interleukin-2 (IL-2) and the responding cell subpopulation was composed of CD4+ T lymphocytes. Furthermore, the proliferation was inhibited in a dose-dependent manner by magnesium. Crystalline NiS also increased significantly the spleen cell proliferative response to concanavalin A (Con A) and lipopolysaccharide (LPS) with magnesium potentiating the combined effects of crystalline NiS and mitogens. Interestingly, crystalline NiS did not show any effect on the induction of IL-2 by Con A. The results described herein suggest that crystalline NiS can potentiate both antigenic (MLR) and mitogenic (Con A and LPS) proliferative responses in vitro. Crystalline NiS appears to potentiate these responses by acting in the form of ionic nickel on several intracellular targets for which magnesium ions have different noncompetitive interactions. The effects of magnesium on the potentiating action of crystalline NiS are different depending upon the type of primary stimulatory signal for proliferation (mitogenic or antigenic).

Towards time-dependent current-density-functional theory in the non-linear regime

NASA Astrophysics Data System (ADS)

Escartín, J. M.; Vincendon, M.; Romaniello, P.; Dinh, P. M.; Reinhard, P.-G.; Suraud, E.

2015-02-01

Time-Dependent Density-Functional Theory (TDDFT) is a well-established theoretical approach to describe and understand irradiation processes in clusters and molecules. However, within the so-called adiabatic local density approximation (ALDA) to the exchange-correlation (xc) potential, TDDFT can show insufficiencies, particularly in violently dynamical processes. This is because within ALDA the xc potential is instantaneous and is a local functional of the density, which means that this approximation neglects memory effects and long-range effects. A way to go beyond ALDA is to use Time-Dependent Current-Density-Functional Theory (TDCDFT), in which the basic quantity is the current density rather than the density as in TDDFT. This has been shown to offer an adequate account of dissipation in the linear domain when the Vignale-Kohn (VK) functional is used. Here, we go beyond the linear regime and we explore this formulation in the time domain. In this case, the equations become very involved making the computation out of reach; we hence propose an approximation to the VK functional which allows us to calculate the dynamics in real time and at the same time to keep most of the physics described by the VK functional. We apply this formulation to the calculation of the time-dependent dipole moment of Ca, Mg and Na2. Our results show trends similar to what was previously observed in model systems or within linear response. In the non-linear domain, our results show that relaxation times do not decrease with increasing deposited excitation energy, which sets some limitations to the practical use of TDCDFT in such a domain of excitations.

Towards time-dependent current-density-functional theory in the non-linear regime.

PubMed

Escartín, J M; Vincendon, M; Romaniello, P; Dinh, P M; Reinhard, P-G; Suraud, E

2015-02-28

Time-Dependent Density-Functional Theory (TDDFT) is a well-established theoretical approach to describe and understand irradiation processes in clusters and molecules. However, within the so-called adiabatic local density approximation (ALDA) to the exchange-correlation (xc) potential, TDDFT can show insufficiencies, particularly in violently dynamical processes. This is because within ALDA the xc potential is instantaneous and is a local functional of the density, which means that this approximation neglects memory effects and long-range effects. A way to go beyond ALDA is to use Time-Dependent Current-Density-Functional Theory (TDCDFT), in which the basic quantity is the current density rather than the density as in TDDFT. This has been shown to offer an adequate account of dissipation in the linear domain when the Vignale-Kohn (VK) functional is used. Here, we go beyond the linear regime and we explore this formulation in the time domain. In this case, the equations become very involved making the computation out of reach; we hence propose an approximation to the VK functional which allows us to calculate the dynamics in real time and at the same time to keep most of the physics described by the VK functional. We apply this formulation to the calculation of the time-dependent dipole moment of Ca, Mg and Na2. Our results show trends similar to what was previously observed in model systems or within linear response. In the non-linear domain, our results show that relaxation times do not decrease with increasing deposited excitation energy, which sets some limitations to the practical use of TDCDFT in such a domain of excitations.

Modeling Rabbit Responses to Single and Multiple Aerosol ...

EPA Pesticide Factsheets

Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev

A test of the embodied simulation theory of object perception: potentiation of responses to artifacts and animals.

PubMed

Matheson, Heath E; White, Nicole C; McMullen, Patricia A

2014-07-01

Theories of embodied object representation predict a tight association between sensorimotor processes and visual processing of manipulable objects. Previous research has shown that object handles can 'potentiate' a manual response (i.e., button press) to a congruent location. This potentiation effect is taken as evidence that objects automatically evoke sensorimotor simulations in response to the visual presentation of manipulable objects. In the present series of experiments, we investigated a critical prediction of the theory of embodied object representations that potentiation effects should be observed with manipulable artifacts but not non-manipulable animals. In four experiments we show that (a) potentiation effects are observed with animals and artifacts; (b) potentiation effects depend on the absolute size of the objects and (c) task context influences the presence/absence of potentiation effects. We conclude that potentiation effects do not provide evidence for embodied object representations, but are suggestive of a more general stimulus-response compatibility effect that may depend on the distribution of attention to different object features.

The properties of single cones isolated from the tiger salamander retina

PubMed Central

Attwell, David; Werblin, Frank S.; Wilson, Martin

1982-01-01

1. The properties of isolated single cones were studied using the voltage-clamp technique, with two micro-electrodes inserted under visual control. 2. Single cones had input resistances, when impaled with two electrodes, of up to 270 MΩ. This is probably lower than the true membrane resistance, because of damage by the impaling electrodes. The cone capacitance was about 85 pF. 3. The cone membrane contains a time-dependent current, IB, controlled by voltage, and a separate photosensitive current. 4. The gated current, IB, is an inward current with a reversal potential around -25 mV. It is activated by hyperpolarization over the range -30 to -80 mV, and at constant voltage obeys first order (exponential) kinetics. The gating time constant is typically 50 ms at the resting potential of -45 mV, rises to 170 ms at -70 mV, and decreases for further hyperpolarization. 5. The spectral sensitivity curve of the cone light response peaks at 620 nm wave-length, and is narrower than the nomogram for vitamin A2-based pigments. The light responses of isolated cones are spectrally univariant. 6. Voltage-clamped photocurrents were recorded at various membrane potentials, for light steps of various intensities. The photocurrent reversed at around -8 mV. The time course of the photocurrent, for a given intensity, was approximately independent of voltage (although its magnitude was voltage-dependent). The shape of the peak current—voltage relation of the light-sensitive current was independent of light intensity (although its magnitude was intensity-dependent). 7. These results can be explained if: (a) light simply changes the number of photosensitive channels open, without altering the properties of an open channel; (b) the reactions controlling the production of internal transmitter, the binding of internal transmitter to the photosensitive channels, and the closing and opening of the channels are unaffected by the electric field in the cone membrane, even though at least some of these reactions take place in the membrane. 8. IB plays only a small role in shaping the cone voltage response to light. ImagesPlate 1 PMID:7131315

Learning-Dependent Potentiation in the Vibrissal Motor Cortex Is Closely Related to the Acquisition of Conditioned Whisker Responses in Behaving Mice

ERIC Educational Resources Information Center

Delgado-Garcia, Jose Maria; Troncoso, Julieta; Munera, Alejandro

2007-01-01

The role of the primary motor cortex in the acquisition of new motor skills was evaluated during classical conditioning of vibrissal protraction responses in behaving mice, using a trace paradigm. Conditioned stimulus (CS) presentation elicited a characteristic field potential in the vibrissal motor cortex, which was dependent on the synchronized…

Nonautonomous dark soliton solutions in two-component Bose—Einstein condensates with a linear time-dependent potential

NASA Astrophysics Data System (ADS)

Li, Qiu-Yan; Wang, Shuang-Jin; Li, Zai-Dong

2014-06-01

We report the analytical nonautonomous soliton solutions (NSSs) for two-component Bose—Einstein condensates with the presence of a time-dependent potential. These solutions show that the time-dependent potential can affect the velocity of NSS. The velocity shows the characteristic of both increasing and oscillation with time. A detailed analysis for the asymptotic behavior of NSSs demonstrates that the collision of two NSSs of each component is elastic.

Refinements in the short-circuit technique and its application to active potassium transport across the cecropia midgut.

PubMed

Wood, J L; Moreton, R B

1978-12-01

1. The conventional, two-electrode method for measuring potential difference across an epithelium is subject to error due to potential gradients caused by current flow in the bathing medium. Mathematical analysis shows that the error in measuring short-circuit current is proportional to the resistivity of the bathing medium and to the separation of the two recording electrodes. It is particularly serious for the insect larval midgut, where the resistivity of the medium is high, and that of the tissue is low. 2. A system has been devised, which uses a third recording electrode to monitor directly the potential gradient in the bathing medium. By suitable electrical connexions, the gradient can be automatically compensated, leaving a residual error which depends on the thickness of the tissue, but not on the electrode separation. Because the thicknesses of most epithelia are smaller than the smallest practical electrode spacing, this error is smaller than that inherent in a two-electrode system. 3. Since voltage-gradients are automatically compensated, it is possible to obtain continuous readings of potential and current. A 'voltage-clamp' circuit is described, which allows the time-course of the short-circuit current to be studied. 4.The three-electrode system has been used to study the larval midgut of Hyalophora cecropia. The average results from five experiments were: initial potential difference (open-circuit): 98+/-11 mV (S.E.M.); short-circuit current at time 60 min: 498+/-160 microA cm=2; 'steady-state' resistance at 60 min: 150+/-26 omega cm2. The current is equivalent to a net potassium transport of 18.6 mu-equiv cm-2 h-1. 5. The electrical parameters of the midgut change rapidly with time. The potential difference decays with a half-time of about 158 min, the resistance increases with a half-time of about 16 min, and the short-circuit current decays as the sum of two exponential terms, with half-times of about 16 and 158 min respectively. In addition, potential and short-circuit current show transient responses to step changes. 6. The properties of the midgut are compared with those of other transporting epithelia, and their dependence on the degree of folding of the preparation is discussed. Their time-dependence is discussed in the context of changes in potassium content of the tissue, and the implications for measurements depending on the assumption of a steady state are outlined.

Rapid hydrogen ion uptake of rod outer segments and rhodopsin solutions on illumination

PubMed Central

Falk, G.; Fatt, P.

1966-01-01

1. Flash illumination of a suspension of frog rod outer segments or rhodopsin solution in contact with a platinum electrode produces a rapidly developing negative displacement of potential of the electrode (with respect to a reversible electrode). 2. The amplitude of the potential change varies inversely with the H+ buffering capacity of the medium. It is inferred that the response is due to an uptake of H+ by the rod outer segments or rhodopsin, with the platinum surface acting as a pH electrode. 3. Determination of the action spectrum shows that the response depends on the absorption of light by rhodopsin. 4. In frog rods one acid-binding group with a pK of about 7·9 is produced for each molecule of rhodopsin bleached, consistent with a rhodopsin concentration in frog rods of 1·7 mM. 5. It is suggested that the time course of the response with rhodopsin solutions reflects the kinetics of the conversion of metarhodopsin I to metarhodopsin II. 6. A slower time course of voltage change observed for suspensions of outer segments is attributable to the time required for the diffusion of H+ buffer out of the rods. PMID:5945249

Effects of premature stimulation on HERG K+ channels

PubMed Central

Lu, Yu; Mahaut-Smith, Martyn P; Varghese, Anthony; Huang, Christopher L-H; Kemp, Paul R; Vandenberg, Jamie I

2001-01-01

The unusual kinetics of human ether-à-go-go-related gene (HERG) K+ channels are consistent with a role in the suppression of arrhythmias initiated by premature beats. Action potential clamp protocols were used to investigate the effect of premature stimulation on HERG K+ channels, transfected in Chinese hamster ovary cells, at 37 °C. HERG K+ channel currents peaked during the terminal repolarization phase of normally paced action potential waveforms. However, the magnitude of the current and the time point at which conductance was maximal depended on the type of action potential waveform used (epicardial, endocardial, Purkinje fibre or atrial). HERG K+ channel currents recorded during premature action potentials consisted of an early transient outward current followed by a sustained outward current. The magnitude of the transient current component showed a biphasic dependence on the coupling interval between the normally paced and premature action potentials and was maximal at a coupling interval equivalent to 90% repolarization (APD90) for ventricular action potentials. The largest transient current response occurred at shorter coupling intervals for Purkinje fibre (APD90– 20 ms) and atrial (APD90– 30 ms) action potentials. The magnitude of the sustained current response following premature stimulation was similar to that recorded during the first action potential for ventricular action potential waveforms. However, for Purkinje and atrial action potentials the sustained current response was significantly larger during the premature action potential than during the normally paced action potential. A Markov model that included three closed states, one open and one inactivated state with transitions permitted between the pre-open closed state and the inactivated state, successfully reproduced our results for the effects of premature stimuli, both during square pulse and action potential clamp waveforms. These properties of HERG K+ channels may help to suppress arrhythmias initiated by early afterdepolarizations and premature beats in the ventricles, Purkinje fibres or atria. PMID:11744759

[Significance of heterogenity in endothelium-dependent vasodilatation occurrence in healthy individuals with or without coronary risk factors].

PubMed

Polovina, Marija; Potpara, Tatjana; Giga, Vojislav; Ostojić, Miodrag

2009-10-01

Brachial artery flow-mediated dilation (FMD) is extensively used for non-invasive assessment of endothelial function. Traditionally, FMD is calculated as a percent change of arterial diameter from the baseline value at an arbitrary time point after cuff deflation (usually 60 seconds). Considerable individual differences in brachial artery temporal response to hyperemic stimulus have been observed, potentially influenced by the presence of atherosclerotic risk factors (RF). The importance of such differences for the evaluation of endothelial function has not been well established. The aim of the study was to determine the time course of maximal brachial artery endothelium-dependent dilation in healthy adults with and without RF, to explore the correlation of RF with brachial artery temporal response and to evaluate the importance of individual differences in temporal response for the assessment of endothelial function. A total of 115 healthy volunteers were included in the study. Out of them, 58 had no RF (26 men, mean age 44 +/-14 years) and 57 had at least one RF (29 men, mean age 45 +/-14 years). High-resolution color Doppler vascular ultrasound was used for brachial artery imaging. To determine maximal arterial diameter after cuff deflation and the time-point of maximal vasodilation off-line sequential measurements were performed every 10 seconds from 0 to 240 seconds after cuff release. True maximal FMD value was calculated as a percent change of the true maximal diameter from the baseline, and compared with FMD value calculated assuming that every participant reached maximal dilation at 60 seconds post cuff deflation (FMD60). Correlation of different RF with brachial artery temporal response was assessed. A maximal brachial artery endothelium-dependent vasodilation occurred from 30-120 seconds after cuff release, and the mean time of endothelium-dependent dilation was 68 +/-20 seconds. Individuals without RF had faster endothelium-dependent dilation (mean time 62 +/-17 seconds), and a shorter time-span (30 to 100 seconds), than participants with RF (mean time 75 +/-21 seconds, time-span 40 to 120 seconds) (p < 0.001). Time when the maximal endothelium-dependent dilation occurred was independently associated with age, serum lipid fractions (total cholesterol, LDL and HDL cholesterol), smoking, physical activity and C-reactive protein. True maximal FMD value in the whole group (6.7 +/-3.0%) was significantly higher (p < 0.001) than FMD60 (5.2 +/-3.5%). The same results were demonstrated for individuals with RF (4.9 +/- 1.7% vs 3.1 +/- 2.3%, p < 0.001) and without RF (8.4 +/- 2.9% vs 7.2 +/- 3.2%, p < 0.05). The temporal response of endothelium-dependent dilation is influenced by the presence of coronary FR and individually heterogeneous. When calculated according to the commonly used approach, i.e. 60 seconds after cuff deflation, FMD is significantly lower than the true maximal FMD. The routinely used measurement time-points for FMD assessment may not be adequate for the detection of true peak vasodilation in individual persons. More precise evaluation of endothelial function can be achieved with sequential measurement of arterial diameter after hyperemic stimulus.

A Benzothiadiazole Primes Parsley Cells for Augmented Elicitation of Defense Responses

PubMed Central

Katz, Vera A.; Thulke, Oliver U.; Conrath, Uwe

1998-01-01

Systemic acquired resistance is an important component of the disease-resistance arsenal of plants, and is associated with an enhanced potency for activating local defense responses upon pathogen attack. Here we demonstrate that pretreatment with benzothiadiazole (BTH), a synthetic activator of acquired resistance in plants, augmented the sensitivity for low-dose elicitation of coumarin phytoalexin secretion by cultured parsley (Petroselinum crispum L.) cells. Enhanced coumarin secretion was associated with potentiated activation of genes encoding Phe ammonia-lyase (PAL). The augmentation of PAL gene induction was proportional to the length of pretreatment with BTH, indicating time-dependent priming of the cells. In contrast to the PAL genes, those for anionic peroxidase were directly induced by BTH in the absence of elicitor, thus confirming a dual role for BTH in the activation of plant defenses. Strikingly, the ability of various chemicals to enhance plant disease resistance correlated with their capability to potentiate parsley PAL gene elicitation, emphasizing an important role for defense response potentiation in acquired plant disease resistance. PMID:9701589

Wave Functions for Time-Dependent Dirac Equation under GUP

NASA Astrophysics Data System (ADS)

Zhang, Meng-Yao; Long, Chao-Yun; Long, Zheng-Wen

2018-04-01

In this work, the time-dependent Dirac equation is investigated under generalized uncertainty principle (GUP) framework. It is possible to construct the exact solutions of Dirac equation when the time-dependent potentials satisfied the proper conditions. In (1+1) dimensions, the analytical wave functions of the Dirac equation under GUP have been obtained for the two kinds time-dependent potentials. Supported by the National Natural Science Foundation of China under Grant No. 11565009

You can't run but you can hide: refuge use in frog tadpoles elicits density-dependent predation by dragonfly larvae.

PubMed

Hossie, Thomas John; Murray, Dennis L

2010-06-01

The potential role of prey refuges in stabilizing predator-prey interactions is of longstanding interest to ecologists, but mechanisms underlying a sigmoidal predator functional response remain to be fully elucidated. Authors have disagreed on whether the stabilizing effect of prey refuges is driven by prey- versus predator-centric mechanisms, but to date few studies have married predator and prey behavioural observations to distinguish between these possibilities. We used a dragonfly nymph-tadpole system to study the effect of a structural refuge (leaf litter) on the predator's functional response, and paired this with behavioural observations of both predator and prey. Our study confirmed that hyperbolic (type II) functional responses were characteristic of foraging predators when structural cover was low or absent, whereas the functional response was sigmoidal (type III) when prey were provided with sufficient refuge. Prey activity and refuge use were density independent across cover treatments, thereby eliminating a prey-centric mechanism as being the genesis for density-dependent predation. In contrast, the predator's pursuit length, capture success, and handling time were altered by the amount of structure implying that observed shifts in density-dependent predation likely were related to predator hunting efficiency. Our study advances current theory by revealing that despite fixed-proportion refuge use by prey, presence of a prey refuge can induce density-dependent predation through its effect on predator hunting strategy. Ultimately, responses of predator foraging decisions in response to changes in prey availability and search efficiency may be more important in producing density-dependent predation than the form of prey refuge use.

Evaluation of Selected Immunomodulatory Glycoproteins as an Adjunct to Cancer Immunotherapy

PubMed Central

Sekhon, Bhagwant Kaur; Li, Yiming; Devi, Parimala B.; Nammi, Srinivas; Fan, Kei

2016-01-01

Polysaccharopeptide (PSP), from Coriolus versicolor, has been used widely as an adjuvant to chemotherapy with demonstrated anti-tumor and broad immunomodulating effects. While PSP’s mechanism of action still remains unknown, its enhanced immunomodulatory potential with acacia gum is of great interest. Acacia gum, which also contains polysaccharides and glycoproteins, has been demonstrated to be immunopotentiating. To elucidate whether PSP directly activates T-cell-dependent B-cell responses in vivo, we used a well-established hapten carrier system (Nitrophenyl-chicken gamma globulin (NP-CGG)). 6-week C57BL/6 male mice were immunised with 50 μg of NP25-CGG alum precipitate intraperitoneally. Mice were gavaged daily with 50mg/kg PSP in a vehicle containing acacia gum and sacrificed at days 0, 4, 7, 10, 14 and 21. ELISA was used to measure the total and relative hapten-specific anti-NP IgA, IgM and IgG titre levels compared to the controls. It was found that PSP, combined with acacia gum, significantly increased total IgG titre levels at day 4 (P< 0.05), decreased IgM titre levels at days 4 and 21 (P< 0.05) with no alterations observed in the IgA or IgE titre levels at any of the time points measured. Our results suggest that while PSP combined with acacia gum appears to exert weak immunological effects through specific T-cell dependent B-cell responses, they are likely to be broad and non-specific which supports the current literature on PSP. We report for the first time the application of a well-established hapten-carrier system that can be used to characterise and delineate specific T-cell dependent B-cell responses of potential immunomodulatory glycoprotein-based herbal medicines combinations in vivo. PMID:26799072

[Optimization of Formulation and Process of Paclitaxel PEGylated Liposomes by Box-Behnken Response Surface Methodology].

PubMed

Shi, Ya-jun; Zhang, Xiao-feil; Guo, Qiu-ting

2015-12-01

To develop a procedure for preparing paclitaxel encapsulated PEGylated liposomes. The membrane hydration followed extraction method was used to prepare PEGylated liposomes. The process and formulation variables were optimized by "Box-Behnken Design (BBD)" of response surface methodology (RSM) with the amount of Soya phosphotidylcholine (SPC) and PEG2000-DSPE as well as the rate of SPC to drug as independent variables and entrapment efficiency as dependent variables for optimization of formulation variables while temperature, pressure and cycle times as independent variables and particle size and polydispersion index as dependent variables for process variables. The optimized liposomal formulation was characterized for particle size, Zeta potential, morphology and in vitro drug release. For entrapment efficiency, particle size, polydispersion index, Zeta potential, and in vitro drug release of PEGylated liposomes was found to be 80.3%, (97.15 ± 14.9) nm, 0.117 ± 0.019, (-30.3 ± 3.7) mV, and 37.4% in 24 h, respectively. The liposomes were found to be small, unilamellar and spherical with smooth surface as seen in transmission electron microscopy. The Box-Behnken response surface methodology facilitates the formulation and optimization of paclitaxel PEGylated liposomes.

Ciprofloxacin provokes SOS-dependent changes in respiration and membrane potential and causes alterations in the redox status of Escherichia coli.

PubMed

Smirnova, Galina V; Tyulenev, Aleksey V; Muzyka, Nadezda G; Peters, Mikhail A; Oktyabrsky, Oleg N

2017-01-01

An in-depth understanding of the physiological response of bacteria to antibiotic-induced stress is needed for development of new approaches to combatting microbial infections. Fluoroquinolone ciprofloxacin causes phase alterations in Escherichia coli respiration and membrane potential that strongly depend on its concentration. Concentrations lower than the optimal bactericidal concentration (OBC) do not inhibit respiration during the first phase. A dose higher than the OBC provokes immediate SOS-independent inhibition of respiration and growth that can contribute to a decreased SOS response and lowered susceptibility to high concentrations of ciprofloxacin. Cells retain their metabolic activity, membrane potential and accelerated K + uptake and produce low levels of superoxide and H 2 O 2 during the first phase. The time before initiation of the second phase is inversely correlated with the ciprofloxacin concentration. The second phase is SOS-dependent and characterized by respiratory inhibition, membrane depolarization, K + and glutathione leakage and cessation of glucose consumption and may be considered as cell death. atpA, gshA and kefBkefC knockouts, which perturb fluxes of protons and K + , can modify the degree and duration of respiratory inhibition and potassium retention. Loss of K + efflux channels KefB and KefC enhances the susceptibility of E. coli to ciprofloxacin. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Cross-adaptation between Olfactory Responses Induced by Two Subgroups of Odorant Molecules

PubMed Central

Takeuchi, Hiroko; Imanaka, Yukie; Hirono, Junzo; Kurahashi, Takashi

2003-01-01

It has long been believed that vertebrate olfactory signal transduction is mediated by independent multiple pathways (using cAMP and InsP3 as second messengers). However, the dual presence of parallel pathways in the olfactory receptor cell is still controversial, mainly because of the lack of information regarding the single-cell response induced by odorants that have been shown to produce InsP3 exclusively (but not cAMP) in the olfactory cilia. In this study, we recorded activities of transduction channels of single olfactory receptor cells to InsP3-producing odorants. When the membrane potential was held at −54 mV, application of InsP3-producing odorants to the ciliary region caused an inward current. The reversal potential was 0 ± 7 mV (mean ± SD, n = 10). Actually, InsP3-producing odorants generated responses in a smaller fraction of cells (lilial, 3.4%; lyral, 1.7%) than the cAMP-producing odorant (cineole, 26%). But, fundamental properties of responses were surprisingly homologous; namely, spatial distribution of the sensitivity, waveforms, I-V relation, and reversal potential, dose dependence, time integration of stimulus period, adaptation, and recovery. By applying both types of odorants alternatively to the same cell, furthermore, we observed cells to exhibit symmetrical cross-adaptation. It seems likely that even with odorants with different modalities adaptation occurs completely depending on the amount of current flow. The data will also provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants. PMID:12939391

Cross-adaptation between olfactory responses induced by two subgroups of odorant molecules.

PubMed

Takeuchi, Hiroko; Imanaka, Yukie; Hirono, Junzo; Kurahashi, Takashi

2003-09-01

It has long been believed that vertebrate olfactory signal transduction is mediated by independent multiple pathways (using cAMP and InsP3 as second messengers). However, the dual presence of parallel pathways in the olfactory receptor cell is still controversial, mainly because of the lack of information regarding the single-cell response induced by odorants that have been shown to produce InsP3 exclusively (but not cAMP) in the olfactory cilia. In this study, we recorded activities of transduction channels of single olfactory receptor cells to InsP3-producing odorants. When the membrane potential was held at -54 mV, application of InsP3-producing odorants to the ciliary region caused an inward current. The reversal potential was 0 +/- 7 mV (mean +/- SD, n = 10). Actually, InsP3-producing odorants generated responses in a smaller fraction of cells (lilial, 3.4%; lyral, 1.7%) than the cAMP-producing odorant (cineole, 26%). But, fundamental properties of responses were surprisingly homologous; namely, spatial distribution of the sensitivity, waveforms, I-V relation, and reversal potential, dose dependence, time integration of stimulus period, adaptation, and recovery. By applying both types of odorants alternatively to the same cell, furthermore, we observed cells to exhibit symmetrical cross-adaptation. It seems likely that even with odorants with different modalities adaptation occurs completely depending on the amount of current flow. The data will also provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants.

Velocity-gauge real-time TDDFT within a numerical atomic orbital basis set

DOE PAGES

Pemmaraju, C. D.; Vila, F. D.; Kas, J. J.; ...

2018-02-07

The interaction of laser fields with solid-state systems can be modeled efficiently within the velocity-gauge formalism of real-time time dependent density functional theory (RT-TDDFT). In this article, we discuss the implementation of the velocity-gauge RT-TDDFT equations for electron dynamics within a linear combination of atomic orbitals (LCAO) basis set framework. Numerical results obtained from our LCAO implementation, for the electronic response of periodic systems to both weak and intense laser fields, are compared to those obtained from established real-space grid and Full-Potential Linearized Augmented Planewave approaches. As a result, potential applications of the LCAO based scheme in the context ofmore » extreme ultra-violet and soft X-ray spectroscopies involving core-electronic excitations are discussed.« less

Velocity-gauge real-time TDDFT within a numerical atomic orbital basis set

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pemmaraju, C. D.; Vila, F. D.; Kas, J. J.

The interaction of laser fields with solid-state systems can be modeled efficiently within the velocity-gauge formalism of real-time time dependent density functional theory (RT-TDDFT). In this article, we discuss the implementation of the velocity-gauge RT-TDDFT equations for electron dynamics within a linear combination of atomic orbitals (LCAO) basis set framework. Numerical results obtained from our LCAO implementation, for the electronic response of periodic systems to both weak and intense laser fields, are compared to those obtained from established real-space grid and Full-Potential Linearized Augmented Planewave approaches. As a result, potential applications of the LCAO based scheme in the context ofmore » extreme ultra-violet and soft X-ray spectroscopies involving core-electronic excitations are discussed.« less

Context-Dependent Plastic Response during Egg-Laying in a Widespread Newt Species

PubMed Central

Tóth, Zoltán

2015-01-01

Previous research on predator-induced phenotypic plasticity mostly focused on responses in morphology, developmental time and/or behaviour during early life stages, but the potential significance of anticipatory parental responses has been investigated less often. In this study I examined behavioural and maternal responses of gravid female smooth newts, Lissotriton vulgaris, in the presence of chemical cues originating from invertebrate predators, Acilius sulcatus water beetles and Aeshna cyanea dragonfly larvae. More specifically, I tested the extent of oviposition preference, plasticity in egg-wrapping behaviour and plasticity in egg size when females had the possibility to lay eggs at oviposition sites with and without predator cues during overnight trials. I found that individuals did not avoid laying eggs in the environment with predator cues; however, individuals that deposited eggs into both environments adjusted the size of the laid eggs to the perceived environment. Females deposited larger eggs earlier in the season but egg size decreased with time in the absence of predator cues, whereas individuals laid eggs of average size throughout the investigated reproductive period when such cues were present. Also, egg size was found to be positively related to hatching success. Individuals did not adjust their wrapping behaviour to the presence of predator cues, but females differed in the extent of egg-wrapping between ponds. Females’ body mass and tail depth were also different between ponds, whereas their body size was positively associated with egg size. According to these results, female smooth newts have the potential to exhibit activational plasticity and invest differently into eggs depending on temporal and environmental factors. Such an anticipatory response may contribute to the success of this caudate species under a wide range of predator regimes at its natural breeding habitats. PMID:26291328

Graphene-hexagonal boron nitride resonant tunneling diodes as high-frequency oscillators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaskell, J.; Fromhold, T. M.; Greenaway, M. T.

We assess the potential of two-terminal graphene-hexagonal boron nitride-graphene resonant tunneling diodes as high-frequency oscillators, using self-consistent quantum transport and electrostatic simulations to determine the time-dependent response of the diodes in a resonant circuit. We quantify how the frequency and power of the current oscillations depend on the diode and circuit parameters including the doping of the graphene electrodes, device geometry, alignment of the graphene lattices, and the circuit impedances. Our results indicate that current oscillations with frequencies of up to several hundred GHz should be achievable.

Drug dependence, parenting responsibilities, and treatment history: why doesn't mom go for help?

PubMed

McMahon, Thomas J; Winkel, Justin D; Suchman, Nancy E; Luthar, Suniya S

2002-01-01

Despite longstanding concern that the presence of children deters drug-dependent women from entering treatment, there have been few empirical tests of the relationship between parenting responsibilities and treatment-seeking behavior. In this study, the relationship between number of biological children and treatment history was examined in a cohort of 153 women seeking methadone maintenance treatment. In a standard multiple regression analysis that also allowed for the potential influence of (a) age, (b) education, (c) ethnic minority status, (d) cohabitation with a sexual partner, (e) chronicity of opioid use, and (f) knowledge of HIV infection, there was a significant, negative relationship between number of children and number of earlier contacts for drug abuse treatment. Ethnic minority status and cohabitation with a sexual partner were also associated with fewer earlier contacts; greater chronicity and knowledge of HIV infection were associated with more earlier contacts. Moreover, there was significant moderation of the negative relationship between parenting responsibilities and treatment history by (a) ethnic minority status, (b) cohabitation, and (c) chronicity of use. Within a cross-sectional research design, the findings highlight ways parenting responsibilities may interact with other factors over time to influence the treatment-seeking behavior of drug-dependent women.

Drug dependence, parenting responsibilities, and treatment history: why doesn’t mom go for help?

PubMed Central

McMahon, Thomas J.; Winkel, Justin D.; Suchman, Nancy E.; Luthar, Suniya S.

2012-01-01

Despite longstanding concern that the presence of children deters drug-dependent women from entering treatment, there have been few empirical tests of the relationship between parenting responsibilities and treatment-seeking behavior. In this study, the relationship between number of biological children and treatment history was examined in a cohort of 153 women seeking methadone maintenance treatment. In a standard multiple regression analysis that also allowed for the potential influence of (a) age, (b) education, (c) ethnic minority status, (d) cohabitation with a sexual partner, (e) chronicity of opioid use, and (f) knowledge of HIV infection, there was a significant, negative relationship between number of children and number of earlier contacts for drug abuse treatment. Ethnic minority status and cohabitation with a sexual partner were also associated with fewer earlier contacts; greater chronicity and knowledge of HIV infection were associated with more earlier contacts. Moreover, there was significant moderation of the negative relationship between parenting responsibilities and treatment history by (a) ethnic minority status, (b) cohabitation, and (c) chronicity of use. Within a cross-sectional research design, the findings highlight ways parenting responsibilities may interact with other factors over time to influence the treatment-seeking behavior of drug-dependent women. PMID:11772472

Neuromodulated Spike-Timing-Dependent Plasticity, and Theory of Three-Factor Learning Rules

PubMed Central

Frémaux, Nicolas; Gerstner, Wulfram

2016-01-01

Classical Hebbian learning puts the emphasis on joint pre- and postsynaptic activity, but neglects the potential role of neuromodulators. Since neuromodulators convey information about novelty or reward, the influence of neuromodulators on synaptic plasticity is useful not just for action learning in classical conditioning, but also to decide “when” to create new memories in response to a flow of sensory stimuli. In this review, we focus on timing requirements for pre- and postsynaptic activity in conjunction with one or several phasic neuromodulatory signals. While the emphasis of the text is on conceptual models and mathematical theories, we also discuss some experimental evidence for neuromodulation of Spike-Timing-Dependent Plasticity. We highlight the importance of synaptic mechanisms in bridging the temporal gap between sensory stimulation and neuromodulatory signals, and develop a framework for a class of neo-Hebbian three-factor learning rules that depend on presynaptic activity, postsynaptic variables as well as the influence of neuromodulators. PMID:26834568

A new ultrasonic transducer sample cell for in situ small-angle scattering experiments

NASA Astrophysics Data System (ADS)

Gupta, Sudipta; Bleuel, Markus; Schneider, Gerald J.

2018-01-01

Ultrasound irradiation is a commonly used technique for nondestructive diagnostics or targeted destruction. We report on a new versatile sonication device that fits in a variety of standard sample environments for neutron and X-ray scattering instruments. A piezoelectric transducer permits measuring of the time-dependent response of the sample in situ during or after sonication. We use small-angle neutron scattering (SANS) to demonstrate the effect of a time-dependent perturbation on the structure factor of micelles formed from sodium dodecyl sulfate surfactant molecules. We observe a substantial change in the micellar structure during and after exposure to ultrasonic irradiation. We also observe a time-dependent relaxation to the equilibrium values of the unperturbed system. The strength of the perturbation of the structure factor depends systematically on the duration of sonication. The relaxation behavior can be well reproduced after multiple times of sonication. Accumulation of the recorded intensities of the different sonication cycles improves the signal-to-noise ratio and permits reaching very short relaxation times. In addition, we present SANS data for the micellar form factor on alkyl-poly (ethylene oxide) surfactant molecules irradiated by ultrasound. Due to the flexibility of our new in situ sonication device, different experiments can be performed, e.g., to explore molecular potentials in more detail by introducing a systematic time-dependent perturbation.

Time-dependent deformation of polymer network in polymer-stabilized cholesteric liquid crystals (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lee, Kyung Min; Tondiglia, Vincent P.; Bunning, Timothy J.; White, Timothy J.

2017-02-01

Recently, we reported direct current (DC) field controllable electro-optic (EO) responses of negative dielectric anisotropy polymer stabilized cholesteric liquid crystals (PSCLCs). A potential mechanism is: Ions in the liquid crystal mixtures are trapped in/on the polymer network during the fast photopolymerization process, and the movement of ions by the application of the DC field distorts polymer network toward the negative electrode, inducing pitch variation through the cell thickness, i.e., pitch compression on the negative electrode side and pitch expansion on positive electrode side. As the DC voltage is directly applied to a target voltage, charged polymer network is deformed and the reflection band is tuned. Interestingly, the polymer network deforms further (red shift of reflection band) with time when constantly applied DC voltage, illustrating DC field induced time dependent deformation of polymer network (creep-like behavior). This time dependent reflection band changes in PSCLCs are investigated by varying the several factors, such as type and concentration of photoinitiators, liquid crystal monomer content, and curing condition (UV intensity and curing time). In addition, simple linear viscoelastic spring-dashpot models, such as 2-parameter Kelvin and 3-parameter linear models, are used to investigate the time-dependent viscoelastic behaviors of polymer networks in PSCLC.

Growth condition dependency is the major cause of non-responsiveness upon genetic perturbation

PubMed Central

Amini, Saman; Holstege, Frank C. P.

2017-01-01

Investigating the role and interplay between individual proteins in biological processes is often performed by assessing the functional consequences of gene inactivation or removal. Depending on the sensitivity of the assay used for determining phenotype, between 66% (growth) and 53% (gene expression) of Saccharomyces cerevisiae gene deletion strains show no defect when analyzed under a single condition. Although it is well known that this non-responsive behavior is caused by different types of redundancy mechanisms or by growth condition/cell type dependency, it is not known what the relative contribution of these different causes is. Understanding the underlying causes of and their relative contribution to non-responsive behavior upon genetic perturbation is extremely important for designing efficient strategies aimed at elucidating gene function and unraveling complex cellular systems. Here, we provide a systematic classification of the underlying causes of and their relative contribution to non-responsive behavior upon gene deletion. The overall contribution of redundancy to non-responsive behavior is estimated at 29%, of which approximately 17% is due to homology-based redundancy and 12% is due to pathway-based redundancy. The major determinant of non-responsiveness is condition dependency (71%). For approximately 14% of protein complexes, just-in-time assembly can be put forward as a potential mechanistic explanation for how proteins can be regulated in a condition dependent manner. Taken together, the results underscore the large contribution of growth condition requirement to non-responsive behavior, which needs to be taken into account for strategies aimed at determining gene function. The classification provided here, can also be further harnessed in systematic analyses of complex cellular systems. PMID:28257504

Endothelin receptors and activity differ in human, dog, and rabbit lung.

PubMed

McKay, K O; Armour, C L; Black, J L

1996-01-01

In this study, we have examined dog and rabbit airways as potential models for human airways in regard to the activity of endothelin. The receptors involved in the response to endothelin-1 (ET-1) in airway tissue from human, rabbit, and dog lung were investigated, as was the mechanism responsible for the contraction to ET-1 in tissue from the three species. By using specific endothelin receptor agonists and antagonists, we have demonstrated that ETB receptors predominate in rabbit and human airways and ETA receptors in dog airways. The contraction to ET-1 is not dependent on cyclooxygenase products of arachidonic acid, as indomethacin had no effect on the response to ET-1. Extracellular calcium influx via voltage-dependent channels is necessary for contraction to ET-1 in rabbit and dog airways. These results are in contrast to our previously reported results in human airways, in which neither removal of extracellular calcium nor verapamil affected the ET-1 response. The sustained phase of the contraction to ET-1 in all three species may be mediated in part by activation of protein kinase C (PKC), as the inhibitor staurosporine significantly altered the time course of the response to endothelin. We therefore conclude that in rabbit airways ET-1 activates ETB receptors, triggers the influx of extracellular calcium through voltage-dependent channels, and induces a contractile response that is, in part, dependent upon stimulation of PKC. The same mechanism is triggered in dog bronchus; however, the receptors involved in this species are of the ETA type. Finally, in human airways, the contractile response to ET-1, while independent of extracellular calcium influx, is dependent upon PKC activation after binding of the peptide to ETB receptors.

Origin and voltage dependence of asparagine-induced depolarization in intestinal cells of Xenopus embryo.

PubMed Central

Bergman, C; Bergman, J

1985-01-01

The kinetics and voltage dependence of asparagine (Asn)-induced depolarization in endoderm cells from Xenopus laevis embryos were analysed using current-clamp techniques. The depolarization is assumed to reflect the activation of an amino acid membrane carrier; it is accompanied by a slight increase in membrane resistance and cannot be explained by only the electrogenic character of the Asn carrier. It is proposed that the Asn depolarization arises, at least in part, from the decrease of the permeability ratio PK/PNa indirectly associated with the Na-coupled amino acid uptake. At room temperature (20-23 degrees C) the Asn response develops according to a single exponential function whose time constant is correlated with the final level of depolarization. Both amplitude and rise time of the depolarization are sensitive to variations of membrane potential and changes in Asn or Na external concentrations. Lowering the temperature decreases the amplitude of the Asn depolarization and increases its rise time with a Q10 factor of two; the kinetics remain of the Michaelis-Menten type, with a marked decrease in delta Emax and no change in Km. When the holding potential is altered by depolarizing and hyperpolarizing currents, the Asn response varies according to a bell-shaped characteristic presenting an optimum near the normal resting level. Membrane depolarizations induced by Na/K-pump inhibitors or high external K concentrations reduce the size of the Asn response; repolarizing the cell by current injection does not reverse the inhibitory effect of external K ions. Hyperpolarizing the membrane with a K-free Ringer solution increases the amplitude of the Asn response. In all these cases a decrease in delta Emax accounts for the apparent voltage sensitivity of the carrier mechanism. When induced by alterations of [K]o, an additional change in Km is observed, suggesting a K/Na-competitive inhibition of the Asn carrier. The results are discussed in terms of the amino acid carrier and passive membrane properties. It is suggested that the outward K-electrochemical gradient contributes an additional source of energy to the Na-dependent Asn uptake. PMID:4057089

Potentialities of mass spectrometry (ICP-MS) for actinides determination in urine.

PubMed

Bouvier-Capely, C; Ritt, J; Baglan, N; Cossonnet, C

2004-05-01

The applicability of inductively coupled plasma-mass spectrometry (ICP-MS) for determining actinides in urine was investigated. Performances of ICP-MS including detection limit and analysis time were studied and compared with alpha spectrometry performances. In the field of individual monitoring of workers, the comparison chart obtained in this study can be used as a guide for medical laboratories to select the most adequate procedure to be carried out depending on the case in question (the radioisotope to be measured, the required sensitivity, and the desired response time).

Lupus high-density lipoprotein induces proinflammatory responses in macrophages by binding lectin-like oxidised low-density lipoprotein receptor 1 and failing to promote activating transcription factor 3 activity.

PubMed

Smith, Carolyne K; Seto, Nickie L; Vivekanandan-Giri, Anuradha; Yuan, Wenmin; Playford, Martin P; Manna, Zerai; Hasni, Sarfaraz A; Kuai, Rui; Mehta, Nehal N; Schwendeman, Anna; Pennathur, Subramaniam; Kaplan, Mariana J

2017-03-01

Recent evidence indicates that high-density lipoprotein (HDL) exerts vasculoprotective activities by promoting activating transcription factor 3 (ATF3), leading to downregulation of toll-like receptor (TLR)-induced inflammatory responses. Systemic lupus erythematosus (SLE) is associated with increased cardiovascular disease risk not explained by the Framingham risk score. Recent studies have indicated oxidised HDL as a possible contributor. We investigated the potential mechanisms by which lupus HDL may lose its anti-inflammatory effects and promote immune dysregulation. Control macrophages were challenged with control and SLE HDL in vitro and examined for inflammatory markers by real-time qRT-PCR, confocal microscopy, ELISA and flow cytometry. Lupus-prone mice were treated with an HDL mimetic (ETC-642) in vivo and inflammatory cytokine levels measured by real-time qRT-PCR and ELISA. Compared with control HDL, SLE HDL activates NFκB, promotes inflammatory cytokine production and fails to block TLR-induced inflammation in control macrophages. This failure of lupus HDL to block inflammatory responses is due to an impaired ability to promote ATF3 synthesis and nuclear translocation. This inflammation is dependent on lectin-like oxidised low-density lipoprotein receptor 1 (LOX1R) binding and rho-associated, coiled-coil containing protein kinase 1 and 2 (ROCK1/2) kinase activity. HDL mimetic-treated lupus mice showed significant ATF3 induction and proinflammatory cytokine abrogation. Lupus HDL promotes proinflammatory responses through NFκB activation and decreased ATF3 synthesis and activity in an LOX1R-dependent and ROCK1/2-dependent manner. HDL mimetics should be explored as potential therapies for inflammation and SLE cardiovascular risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The semantic origin of unconscious priming: Behavioral and event-related potential evidence during category congruency priming from strongly and weakly related masked words.

PubMed

Ortells, Juan J; Kiefer, Markus; Castillo, Alejandro; Megías, Montserrat; Morillas, Alejandro

2016-01-01

The mechanisms underlying masked congruency priming, semantic mechanisms such as semantic activation or non-semantic mechanisms, for example response activation, remain a matter of debate. In order to decide between these alternatives, reaction times (RTs) and event-related potentials (ERPs) were recorded in the present study, while participants performed a semantic categorization task on visible word targets that were preceded either 167 ms (Experiment 1) or 34 ms before (Experiment 2) by briefly presented (33 ms) novel (unpracticed) masked prime words. The primes and targets belonged to different categories (unrelated), or they were either strongly or weakly semantically related category co-exemplars. Behavioral (RT) and electrophysiological masked congruency priming effects were significantly greater for strongly related pairs than for weakly related pairs, indicating a semantic origin of effects. Priming in the latter condition was not statistically reliable. Furthermore, priming effects modulated the N400 event-related potential (ERP) component, an electrophysiological index of semantic processing, but not ERPs in the time range of the N200 component, associated with response conflict and visuo-motor response priming. The present results demonstrate that masked congruency priming from novel prime words also depends on semantic processing of the primes and is not exclusively driven by non-semantic mechanisms such as response activation. Copyright © 2015 Elsevier B.V. All rights reserved.

Time-local equation for exact time-dependent optimized effective potential in time-dependent density functional theory

NASA Astrophysics Data System (ADS)

Liao, Sheng-Lun; Ho, Tak-San; Rabitz, Herschel; Chu, Shih-I.

2017-04-01

Solving and analyzing the exact time-dependent optimized effective potential (TDOEP) integral equation has been a longstanding challenge due to its highly nonlinear and nonlocal nature. To meet the challenge, we derive an exact time-local TDOEP equation that admits a unique real-time solution in terms of time-dependent Kohn-Sham orbitals and effective memory orbitals. For illustration, the dipole evolution dynamics of a one-dimension-model chain of hydrogen atoms is numerically evaluated and examined to demonstrate the utility of the proposed time-local formulation. Importantly, it is shown that the zero-force theorem, violated by the time-dependent Krieger-Li-Iafrate approximation, is fulfilled in the current TDOEP framework. This work was partially supported by DOE.

Nanoparticle heterodimers: The role of size and interparticle gap distance on the optical response

NASA Astrophysics Data System (ADS)

Mokkath, Junais Habeeb

2018-05-01

Composite plasmonic nanostructures with controlled size, shape and relative arrangement is a subject of significant current research interest. Much of this is stimulated by the prospects by generating enormous near-field enhancements of the surface and interparticle gap regions for potential applications in surface-enhanced spectroscopies. In this manuscript, using time-dependent density functional theory (TDDFT) calculations, we investigate how the optical response in size matched homodimers and size mismatched heterodimers composed of Aluminum modify while varying the size and interparticle gap distances in the sub-nanometer range. Both systems show interesting optical response evolution. In particular, the size mismatched heterodimers show even more complex optical response evolution due to a symmetry-breaking in the system.

Possible relationship between endocrine disrupting chemicals and hormone dependent gynecologic cancers.

PubMed

Dogan, Selen; Simsek, Tayup

2016-07-01

The effects of the natural and synthetic estrogens have been studied for a long time but the data regarding estrogen related chemicals (endocrine disrupting chemicals, EDCs) and their effects on reproductive system are scarce. EDCs are hormone like agents that are readily present in the environment, which may alter the endocrine system of humans and animals. Approximately 800 chemicals are known or suspected to have the potential to function as EDC. Potential role of EDCs on reproductive disease has gained attention in medical literature in recent years. We hypothesize that exposure to low doses of EDCs in a chronic manner could cause hormone dependent genital cancers including ovarian and endometrial cancer. Long term exposure to low concentrations of EDCs may exert potentiation effect with each other and even with endogenous estrogens and could inhibit enzymes responsible for estrogen metabolism. Exposure time to these EDCs is essential as we have seen from Diethylstilbestrol experience. Dose-response curves of EDCs are also unpredictable. Hence mode of action of EDCs are more complex than previously thought. In the light of these controversies lower doses of EDCs in long term exposure is not harmless. Possibility of this relationship and this hypothesis merit further investigation especially through in vivo studies that could better show the realistic environmental exposure. With the confirmation of our hypothesis, possible EDCs could be identified and eliminated from general use as a public health measure. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials and refractory using the Nucleus 24 standard].

PubMed

Ma, R Y; Li, W; Jiang, X J

2016-12-01

Objective: To investigate the correlation between the site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials. Method: Recordings of auditory nerve responses were conducted in 32 prelingual subjects to demonstrate the feasibility of ECAP recordings using the nerve response telemetry(NRT) feature of the Nucleus CI24R(CA) system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation. Result: Findings of our prelingual children showed significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function hadbeen observed. The refractory time showed an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions. Conclusion: Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences between prelingual children and adults could be explained by the location of the stimulating electrode with respect to the neural tissue in the cochlea, a higher density, or an increased neural survival rate of neural tissue in the apex. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Escartín, J. M.; CNRS, UMR5152, F-31062 Toulouse Cedex; Theory of Condensed Matter Group, Cavendish Laboratory, University of Cambridge, J.J. Thomson Avenue, Cambridge CB3 0HE

Time-Dependent Density-Functional Theory (TDDFT) is a well-established theoretical approach to describe and understand irradiation processes in clusters and molecules. However, within the so-called adiabatic local density approximation (ALDA) to the exchange-correlation (xc) potential, TDDFT can show insufficiencies, particularly in violently dynamical processes. This is because within ALDA the xc potential is instantaneous and is a local functional of the density, which means that this approximation neglects memory effects and long-range effects. A way to go beyond ALDA is to use Time-Dependent Current-Density-Functional Theory (TDCDFT), in which the basic quantity is the current density rather than the density as in TDDFT.more » This has been shown to offer an adequate account of dissipation in the linear domain when the Vignale-Kohn (VK) functional is used. Here, we go beyond the linear regime and we explore this formulation in the time domain. In this case, the equations become very involved making the computation out of reach; we hence propose an approximation to the VK functional which allows us to calculate the dynamics in real time and at the same time to keep most of the physics described by the VK functional. We apply this formulation to the calculation of the time-dependent dipole moment of Ca, Mg and Na{sub 2}. Our results show trends similar to what was previously observed in model systems or within linear response. In the non-linear domain, our results show that relaxation times do not decrease with increasing deposited excitation energy, which sets some limitations to the practical use of TDCDFT in such a domain of excitations.« less

Interfacial ionic 'liquids': connecting static and dynamic structures

DOE PAGES

Uysal, Ahmet; Zhou, Hua; Feng, Guang; ...

2014-12-05

It is well known that room temperature ionic liquids (RTILs) often adopt a charge-separated layered structure, i.e. with alternating cation- and anion-rich layers, at electrified interfaces. However, the dynamic response of the layered structure to temporal variations in applied potential is not well understood. For this research, we used in situ, real-time x-ray reflectivity to study the potential-dependent electric double layer (EDL) structure of an imidazolium-based RTIL on charged epitaxial graphene during potential cycling as a function of temperature. The results suggest that the graphene–RTIL interfacial structure is bistable in which the EDL structure at any intermediate potential can bemore » described by the combination of two extreme-potential structures whose proportions vary depending on the polarity and magnitude of the applied potential. This picture is supported by the EDL structures obtained by fully atomistic molecular dynamics simulations at various static potentials. Lastly, the potential-driven transition between the two structures is characterized by an increasing width but with an approximately fixed hysteresis magnitude as a function of temperature. The results are consistent with the coexistence of distinct anion- and cation-adsorbed structures separated by an energy barrier (~0.15 eV).« less

Interfacial ionic 'liquids': connecting static and dynamic structures.

PubMed

Uysal, Ahmet; Zhou, Hua; Feng, Guang; Lee, Sang Soo; Li, Song; Cummings, Peter T; Fulvio, Pasquale F; Dai, Sheng; McDonough, John K; Gogotsi, Yury; Fenter, Paul

2015-01-28

It is well known that room temperature ionic liquids (RTILs) often adopt a charge-separated layered structure, i.e. with alternating cation- and anion-rich layers, at electrified interfaces. However, the dynamic response of the layered structure to temporal variations in applied potential is not well understood. We used in situ, real-time x-ray reflectivity to study the potential-dependent electric double layer (EDL) structure of an imidazolium-based RTIL on charged epitaxial graphene during potential cycling as a function of temperature. The results suggest that the graphene-RTIL interfacial structure is bistable in which the EDL structure at any intermediate potential can be described by the combination of two extreme-potential structures whose proportions vary depending on the polarity and magnitude of the applied potential. This picture is supported by the EDL structures obtained by fully atomistic molecular dynamics simulations at various static potentials. The potential-driven transition between the two structures is characterized by an increasing width but with an approximately fixed hysteresis magnitude as a function of temperature. The results are consistent with the coexistence of distinct anion- and cation-adsorbed structures separated by an energy barrier (∼0.15 eV).

Trans-generational responses to low pH depend on parental gender in a calcifying tubeworm

PubMed Central

Lane, Ackley; Campanati, Camilla; Dupont, Sam; Thiyagarajan, Vengatesen

2015-01-01

The uptake of anthropogenic CO2 emissions by oceans has started decreasing pH and carbonate ion concentrations of seawater, a process called ocean acidification (OA). Occurring over centuries and many generations, evolutionary adaptation and epigenetic transfer will change species responses to OA over time. Trans-generational responses, via genetic selection or trans-generational phenotypic plasticity, differ depending on species and exposure time as well as differences between individuals such as gender. Males and females differ in reproductive investment and egg producing females may have less energy available for OA stress responses. By crossing eggs and sperm from the calcareous tubeworm Hydroides elegans (Haswell, 1883) raised in ambient (8.1) and low (7.8) pH environments, we observed that paternal and maternal low pH experience had opposite and additive effects on offspring. For example, when compared to offspring with both parents from ambient pH, growth rates of offspring of fathers or mothers raised in low pH were higher or lower respectively, but there was no difference when both parents were from low pH. Gender differences may result in different selection pressures for each gender. This may result in overestimates of species tolerance and missed opportunities of potentially insightful comparisons between individuals of the same species. PMID:26039184

Time dependent density functional calculation of plasmon response in clusters

NASA Astrophysics Data System (ADS)

Wang, Feng; Zhang, Feng-Shou; Eric, Suraud

2003-02-01

We have introduced a theoretical scheme for the efficient description of the optical response of a cluster based on the time-dependent density functional theory. The practical implementation is done by means of the fully fledged time-dependent local density approximation scheme, which is solved directly in the time domain without any linearization. As an example we consider the simple Na2 cluster and compute its surface plasmon photoabsorption cross section, which is in good agreement with the experiments.

Delay selection by spike-timing-dependent plasticity in recurrent networks of spiking neurons receiving oscillatory inputs.

PubMed

Kerr, Robert R; Burkitt, Anthony N; Thomas, Doreen A; Gilson, Matthieu; Grayden, David B

2013-01-01

Learning rules, such as spike-timing-dependent plasticity (STDP), change the structure of networks of neurons based on the firing activity. A network level understanding of these mechanisms can help infer how the brain learns patterns and processes information. Previous studies have shown that STDP selectively potentiates feed-forward connections that have specific axonal delays, and that this underlies behavioral functions such as sound localization in the auditory brainstem of the barn owl. In this study, we investigate how STDP leads to the selective potentiation of recurrent connections with different axonal and dendritic delays during oscillatory activity. We develop analytical models of learning with additive STDP in recurrent networks driven by oscillatory inputs, and support the results using simulations with leaky integrate-and-fire neurons. Our results show selective potentiation of connections with specific axonal delays, which depended on the input frequency. In addition, we demonstrate how this can lead to a network becoming selective in the amplitude of its oscillatory response to this frequency. We extend this model of axonal delay selection within a single recurrent network in two ways. First, we show the selective potentiation of connections with a range of both axonal and dendritic delays. Second, we show axonal delay selection between multiple groups receiving out-of-phase, oscillatory inputs. We discuss the application of these models to the formation and activation of neuronal ensembles or cell assemblies in the cortex, and also to missing fundamental pitch perception in the auditory brainstem.

Delay Selection by Spike-Timing-Dependent Plasticity in Recurrent Networks of Spiking Neurons Receiving Oscillatory Inputs

PubMed Central

Kerr, Robert R.; Burkitt, Anthony N.; Thomas, Doreen A.; Gilson, Matthieu; Grayden, David B.

2013-01-01

Learning rules, such as spike-timing-dependent plasticity (STDP), change the structure of networks of neurons based on the firing activity. A network level understanding of these mechanisms can help infer how the brain learns patterns and processes information. Previous studies have shown that STDP selectively potentiates feed-forward connections that have specific axonal delays, and that this underlies behavioral functions such as sound localization in the auditory brainstem of the barn owl. In this study, we investigate how STDP leads to the selective potentiation of recurrent connections with different axonal and dendritic delays during oscillatory activity. We develop analytical models of learning with additive STDP in recurrent networks driven by oscillatory inputs, and support the results using simulations with leaky integrate-and-fire neurons. Our results show selective potentiation of connections with specific axonal delays, which depended on the input frequency. In addition, we demonstrate how this can lead to a network becoming selective in the amplitude of its oscillatory response to this frequency. We extend this model of axonal delay selection within a single recurrent network in two ways. First, we show the selective potentiation of connections with a range of both axonal and dendritic delays. Second, we show axonal delay selection between multiple groups receiving out-of-phase, oscillatory inputs. We discuss the application of these models to the formation and activation of neuronal ensembles or cell assemblies in the cortex, and also to missing fundamental pitch perception in the auditory brainstem. PMID:23408878

Time-dependent LXR/RXR pathway modulation characterizes capillary remodeling in inflammatory corneal neovascularization.

PubMed

Mukwaya, Anthony; Lennikov, Anton; Xeroudaki, Maria; Mirabelli, Pierfrancesco; Lachota, Mieszko; Jensen, Lasse; Peebo, Beatrice; Lagali, Neil

2018-05-01

Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a model of endogenous resolution of inflammation-induced corneal angiogenesis, we investigate the time dependence of inflammatory genes in effecting capillary regression and the return of corneal transparency. Endogenous capillary regression was characterized by a progressive thinning and remodeling of angiogenic capillaries and inflammatory cell retreat in vivo in the rat cornea. By whole-genome longitudinal microarray analysis, early suppression of VEGF ligand-receptor signaling and inflammatory pathways preceded an unexpected later-phase preferential activation of LXR/RXR, PPARα/RXRα and STAT3 canonical pathways, with a concurrent attenuation of LPS/IL-1 inhibition of RXR function and Wnt/β-catenin signaling pathways. Potent downstream inflammatory cytokines such as Cxcl5, IL-1β, IL-6 and Ccl2 were concomitantly downregulated during the remodeling phase. Upstream regulators of the inflammatory pathways included Socs3, Sparc and ApoE. A complex and coordinated time-dependent interplay between pro- and anti-inflammatory signaling pathways highlights a potential anti-inflammatory role of LXR/RXR, PPARα/RXRα and STAT3 signaling pathways in resolving inflammatory corneal angiogenesis.

Calcium dobesilate potentiates endothelium-derived hyperpolarizing factor-mediated relaxation of human penile resistance arteries

PubMed Central

Angulo, Javier; Cuevas, Pedro; Fernández, Argentina; Gabancho, Sonia; Videla, Sebastián; Tejada, Iñigo Sáenz de

2003-01-01

We have evaluated the participation of endothelium-derived hyperpolarizing factor (EDHF) in the endothelium-dependent relaxation of isolated human penile resistance arteries (HPRA) and human corpus cavernosum (HCC) strips. In addition, the effect of the angioprotective agent, calcium dobesilate (DOBE), on the endothelium-dependent relaxation of these tissues was investigated. Combined inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) nearly abolished the endothelium-dependent relaxation to acetylcholine (ACh) in HCC, while 60% relaxation of HPRA was observed under these conditions. Endothelium-dependent relaxation of HPRA resistant to NOS and COX inhibition was prevented by raising the extracellular concentration of K+ (35 mM) or by blocking Ca2+-activated K+ channels, with apamin (APA; 100 nM) and charybdotoxin (CTX; 100 nM), suggesting the involvement of EDHF in these responses. Endothelium-dependent relaxation to ACh was markedly enhanced by DOBE (10 μM) in HPRA but not in HCC. The potentiating effects of DOBE on ACh-induced responses in HPRA, remained after NOS and COX inhibition, were reduced by inhibition of cytochrome P450 oxygenase with miconazole (0.3 mM) and were abolished by high K+ or a combination of APA and CTX. In vivo, DOBE (10 mg kg−1 i.v.) significantly potentiated the erectile responses to cavernosal nerve stimulation in male rats. EDHF plays an important role in the endothelium-dependent relaxation of HPRA but not in HCC. DOBE significantly improves endothelium-dependent relaxation of HPRA mediated by EDHF and potentiates erectile responses in vivo. Thus, EDHF becomes a new therapeutic target for the treatment of erectile dysfunction (ED) and DOBE could be considered a candidate for oral therapy for ED. PMID:12813009

HSV-I and the cellular DNA damage response.

PubMed

Smith, Samantha; Weller, Sandra K

2015-04-01

Peter Wildy first observed genetic recombination between strains of HSV in 1955. At the time, knowledge of DNA repair mechanisms was limited, and it has only been in the last decade that particular DNA damage response (DDR) pathways have been examined in the context of viral infections. One of the first reports addressing the interaction between a cellular DDR protein and HSV-1 was the observation by Lees-Miller et al . that DNA-dependent protein kinase catalytic subunit levels were depleted in an ICP0-dependent manner during Herpes simplex virus 1 infection. Since then, there have been numerous reports describing the interactions between HSV infection and cellular DDR pathways. Due to space limitations, this review will focus predominantly on the most recent observations regarding how HSV navigates a potentially hostile environment to replicate its genome.

An electrophysiological study of task demands on concreteness effects: evidence for dual coding theory.

PubMed

Welcome, Suzanne E; Paivio, Allan; McRae, Ken; Joanisse, Marc F

2011-07-01

We examined ERP responses during the generation of word associates or mental images in response to concrete and abstract concepts. Of interest were the predictions of dual coding theory (DCT), which proposes that processing lexical concepts depends on functionally independent but interconnected verbal and nonverbal systems. ERP responses were time-locked to either stimulus onset or response to compensate for potential latency differences across conditions. During word associate generation, but not mental imagery, concrete items elicited a greater N400 than abstract items. A concreteness effect emerged at a later time point during the mental imagery task. Data were also analyzed using time-frequency analysis that investigated synchronization of neuronal populations over time during processing. Concrete words elicited an enhanced late going desynchronization of theta-band power (723-938 ms post stimulus onset) during associate generation. During mental imagery, abstract items elicited greater delta-band power from 800 to 1,000 ms following stimulus onset, theta-band power from 350 to 205 ms before response, and alpha-band power from 900 to 800 ms before response. Overall, the findings support DCT in suggesting that lexical concepts are not amodal and that concreteness effects are modulated by tasks that focus participants on verbal versus nonverbal, imagery-based knowledge.

Efficient exact-exchange time-dependent density-functional theory methods and their relation to time-dependent Hartree-Fock.

PubMed

Hesselmann, Andreas; Görling, Andreas

2011-01-21

A recently introduced time-dependent exact-exchange (TDEXX) method, i.e., a response method based on time-dependent density-functional theory that treats the frequency-dependent exchange kernel exactly, is reformulated. In the reformulated version of the TDEXX method electronic excitation energies can be calculated by solving a linear generalized eigenvalue problem while in the original version of the TDEXX method a laborious frequency iteration is required in the calculation of each excitation energy. The lowest eigenvalues of the new TDEXX eigenvalue equation corresponding to the lowest excitation energies can be efficiently obtained by, e.g., a version of the Davidson algorithm appropriate for generalized eigenvalue problems. Alternatively, with the help of a series expansion of the new TDEXX eigenvalue equation, standard eigensolvers for large regular eigenvalue problems, e.g., the standard Davidson algorithm, can be used to efficiently calculate the lowest excitation energies. With the help of the series expansion as well, the relation between the TDEXX method and time-dependent Hartree-Fock is analyzed. Several ways to take into account correlation in addition to the exact treatment of exchange in the TDEXX method are discussed, e.g., a scaling of the Kohn-Sham eigenvalues, the inclusion of (semi)local approximate correlation potentials, or hybrids of the exact-exchange kernel with kernels within the adiabatic local density approximation. The lowest lying excitations of the molecules ethylene, acetaldehyde, and pyridine are considered as examples.

Considering Time-Dependency of Social Vulnerability in Crisis Modeling and Management

NASA Astrophysics Data System (ADS)

Aubrecht, C.; Steinnocher, K.; Freire, S.; Loibl, W.; Peters-Anders, J.; Ungar, J.

2012-04-01

Crisis and disaster management is much more than the immediate first-response actions following an incident. In many projects the main focus has been on the phase starting at the point when an unwanted event happens and lasting until the activities return to normal routines (i.e., ad hoc reaction rather than proactive mitigation). There has been less emphasis on the other phases of the disaster management cycle such as prevention, preparedness, recovery and reconstruction, even though those phases have a strong influence on the general status of a society and its citizens. Especially the potential of a crisis to escalate into a large-scale disaster is heavily dependent on the overall level of preparedness as well as on the planning of mitigation and response actions and their timely execution. There is a need for improved decision-making support that enables modeling of different crisis scenarios and their impacts according to chosen prevention and response actions. Vulnerability describing the status of a society with respect to an imposed hazard or potential impact is considered a strongly multidisciplinary concept. A central objective of vulnerability assessment is to provide indications where and how people - and more specifically, what kind of people - might be affected by a certain impact. Results should provide decision- and policy-makers with supporting information to target response and mitigation actions adequately. For assessment of the social dimension of vulnerability, population exposure mapping is usually considered the starting point. Integration of social structure and varying aspects of resilience further differentiate situation-specific vulnerability patterns on a local scale. In a disaster risk management context, assessment of human vulnerability has generally been lagging behind hazard analysis efforts. Accurately estimating population exposure is a key component of catastrophe loss modeling, one element of effective integrated risk analysis and emergency management. The vulnerability of each relevant element at risk, including human beings and society in general and its time-dependent variation is characterized both by its pre-event status and by its possible evolution during a crisis. Particularly in metropolitan areas, the spatial distribution of population is highly time-dependent due to human activities and mobility. Identifying distinct day-/nighttime population distribution characteristics is a major improvement compared to standard residence-based models, but does however only display part of reality. New technologies and data processing capabilities allow moving into the field of real-time representation of human movement. The focus of this contribution will be on illustrating, through project examples and by putting it in an emergency and crisis management context, two main categories, (1) the mapping of cell phone user activity, and (2) the use of volunteered geographic information (VGI).

Global and Regional Temperature-change Potentials for Near-term Climate Forcers

NASA Technical Reports Server (NTRS)

Collins, W.J.; Fry, M. M.; Yu, H.; Fuglestvedt, J. S.; Shindell, D. T.; West, J. J.

2013-01-01

The emissions of reactive gases and aerosols can affect climate through the burdens of ozone, methane and aerosols, having both cooling and warming effects. These species are generally referred to near-term climate forcers (NTCFs) or short-lived climate pollutants (SLCPs), because of their short atmospheric residence time. The mitigation of these would be attractive for both air quality and climate on a 30-year timescale, provided it is not at the expense of CO2 mitigation. In this study we examine the climate effects of the emissions of NTCFs from 4 continental regions (East Asia, Europe, North America and South Asia) using results from the Task Force on Hemispheric Transport of Air Pollution Source-Receptor global chemical transport model simulations. We address 3 aerosol species (sulphate, particulate organic matter and black carbon - BC) and 4 ozone precursors (methane, reactive nitrogen oxides - NOx, volatile organic compounds VOC, and carbon monoxide - CO). For the aerosols the global warming potentials (GWPs) and global temperature change potentials (GTPs) are simply time-dependent scaling of the equilibrium radiative forcing, with the GTPs decreasing more rapidly with time than the GWPs. While the aerosol climate metrics have only a modest dependence on emission region, emissions of NOx and VOCs from South Asia have GWPs and GTPs of higher magnitude than from the other northern hemisphere regions. On regional basis, the northern mid-latitude temperature response to northern mid-latitude emissions is approximately twice as large as the global average response for aerosol emission, and about 20-30% larger than the global average for methane, VOC and CO emissions. We also found that temperatures in the Arctic latitudes appear to be particularly sensitive to black carbon emissions from South Asia.

Salvage therapy for CLL and the role of stem cell transplantation.

PubMed

Gribben, John G

2005-01-01

Chronic lymphocytic leukaemia (CLL) remains an incurable disease and, notwithstanding the excellent remission rates now achieved with purine analogs and monoclonal antibodies, the vast majority of patients with CLL are destined to relapse after primary treatment. The management of relapsed CLL patients is then dependent upon a number of factors, most importantly age, performance status, previous therapy administered, the response and duration of response to such therapy, and time from last therapy. Although prior therapy and response to such therapy are important factors in determining next therapy, it is often difficult to determine their importance from published studies. Furthermore, the goal of therapy, whether palliative or aggressive, must also be weighed into the decision when deciding on the next line of treatment. With many potential treatments available, the sequence of treatments and the timing of procedures such as stem cell transplantation remain controversial and are the focus of ongoing clinical trials.

The importance of decision onset

PubMed Central

Grinband, Jack; Ferrera, Vincent

2015-01-01

The neural mechanisms of decision making are thought to require the integration of evidence over time until a response threshold is reached. Much work suggests that response threshold can be adjusted via top-down control as a function of speed or accuracy requirements. In contrast, the time of integration onset has received less attention and is believed to be determined mostly by afferent or preprocessing delays. However, a number of influential studies over the past decade challenge this assumption and begin to paint a multifaceted view of the phenomenology of decision onset. This review highlights the challenges involved in initiating the integration of evidence at the optimal time and the potential benefits of adjusting integration onset to task demands. The review outlines behavioral and electrophysiolgical studies suggesting that the onset of the integration process may depend on properties of the stimulus, the task, attention, and response strategy. Most importantly, the aggregate findings in the literature suggest that integration onset may be amenable to top-down regulation, and may be adjusted much like response threshold to exert cognitive control and strategically optimize the decision process to fit immediate behavioral requirements. PMID:26609111

Strong-field ionization of Li and Be: a time-dependent density functional theory with self-interaction correction

NASA Astrophysics Data System (ADS)

Telnov, Dmitry A.; Heslar, John T.; Chu, Shih-I.

2011-11-01

In the framework of the time-dependent density functional theory, we have performed 3D calculations of multiphoton ionization of Li and Be atoms by strong near-infrared laser fields. The results for the intensity-dependent probabilities of single and double ionization are presented. We make use of the time-dependent Krieger-Li-Iafrate exchange-correlation potential with self-interaction correction (TD-KLI-SIC). Such a potential possesses an integer discontinuity which improves description of the ionization process. However, we have found that the discontinuity of the TD-KLI-SIC potential is not sufficient to reproduce characteristic feature of double ionization.

Coordinated Pulses of mRNA and of Protein Translation or Degradation Produce EGF-Induced Protein Bursts.

PubMed

Golan-Lavi, Roni; Giacomelli, Chiara; Fuks, Garold; Zeisel, Amit; Sonntag, Johanna; Sinha, Sanchari; Köstler, Wolfgang; Wiemann, Stefan; Korf, Ulrike; Yarden, Yosef; Domany, Eytan

2017-03-28

Protein responses to extracellular cues are governed by gene transcription, mRNA degradation and translation, and protein degradation. In order to understand how these time-dependent processes cooperate to generate dynamic responses, we analyzed the response of human mammary cells to the epidermal growth factor (EGF). Integrating time-dependent transcript and protein data into a mathematical model, we inferred for several proteins their pre-and post-stimulus translation and degradation coefficients and found that they exhibit complex, time-dependent variation. Specifically, we identified strategies of protein production and degradation acting in concert to generate rapid, transient protein bursts in response to EGF. Remarkably, for some proteins, for which the response necessitates rapidly decreased abundance, cells exhibit a transient increase in the corresponding degradation coefficient. Our model and analysis allow inference of the kinetics of mRNA translation and protein degradation, without perturbing cells, and open a way to understanding the fundamental processes governing time-dependent protein abundance profiles. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Time-dependent behavior of passive skeletal muscle

NASA Astrophysics Data System (ADS)

Ahamed, T.; Rubin, M. B.; Trimmer, B. A.; Dorfmann, L.

2016-03-01

An isotropic three-dimensional nonlinear viscoelastic model is developed to simulate the time-dependent behavior of passive skeletal muscle. The development of the model is stimulated by experimental data that characterize the response during simple uniaxial stress cyclic loading and unloading. Of particular interest is the rate-dependent response, the recovery of muscle properties from the preconditioned to the unconditioned state and stress relaxation at constant stretch during loading and unloading. The model considers the material to be a composite of a nonlinear hyperelastic component in parallel with a nonlinear dissipative component. The strain energy and the corresponding stress measures are separated additively into hyperelastic and dissipative parts. In contrast to standard nonlinear inelastic models, here the dissipative component is modeled using an evolution equation that combines rate-independent and rate-dependent responses smoothly with no finite elastic range. Large deformation evolution equations for the distortional deformations in the elastic and in the dissipative component are presented. A robust, strongly objective numerical integration algorithm is used to model rate-dependent and rate-independent inelastic responses. The constitutive formulation is specialized to simulate the experimental data. The nonlinear viscoelastic model accurately represents the time-dependent passive response of skeletal muscle.

A cognitive stressor for event-related potential studies: the Portland arithmetic stress task.

PubMed

Atchley, Rachel; Ellingson, Roger; Klee, Daniel; Memmott, Tabatha; Oken, Barry

2017-05-01

In this experiment, we developed and evaluated the Portland Arithmetic Stress Task (PAST) as a cognitive stressor to evaluate acute and sustained stress reactivity for event-related potential (ERP) studies. The PAST is a titrated arithmetic task adapted from the Montreal Imaging Stress Task (MIST), with added experimental control over presentation parameters, improved and synchronized acoustic feedback and generation of timing markers needed for physiological analyzes of real-time brain activity. Thirty-one older adults (M = 60 years) completed the PAST. EEG was recorded to assess feedback-related negativity (FRN) and the magnitude of the stress response through autonomic nervous system activity and salivary cortisol. Physiological measures other than EEG included heart rate, respiration rate, heart rate variability, blood pressure and salivary cortisol. These measures were collected at several time points throughout the task. Feedback-related negativity evoked-potential responses were elicited and they significantly differed depending on whether positive or negative feedback was received. The PAST also increased systolic blood pressure, heart rate variability and respiration rates compared to a control condition attentional task. These preliminary results suggest that the PAST is an effective cognitive stressor. Successful measurement of the feedback-related negativity suggests that the PAST is conducive to EEG and time-sensitive ERP experiments. Moreover, the physiological findings support the PAST as a potent method for inducing stress in older adult participants. Further research is needed to confirm these results, but the PAST shows promise as a tool for cognitive stress induction for time-locked event-related potential experiments.

The effect of loading time on flexible pavement dynamic response: a finite element analysis

NASA Astrophysics Data System (ADS)

Yin, Hao; Solaimanian, Mansour; Kumar, Tanmay; Stoffels, Shelley

2007-12-01

Dynamic response of asphalt concrete (AC) pavements under moving load is a key component for accurate prediction of flexible pavement performance. The time and temperature dependency of AC materials calls for utilizing advanced material characterization and mechanistic theories, such as viscoelasticity and stress/strain analysis. In layered elastic analysis, as implemented in the new Mechanistic-Empirical Pavement Design Guide (MEPDG), the time dependency is accounted for by calculating the loading times at different AC layer depths. In this study, the time effect on pavement response was evaluated by means of the concept of “pseudo temperature.” With the pavement temperature measured from instrumented thermocouples, the time and temperature dependency of AC materials was integrated into one single factor, termed “effective temperature.” Via this effective temperature, pavement responses under a transient load were predicted through finite element analysis. In the finite element model, viscoelastic behavior of AC materials was characterized through relaxation moduli, while the layers with unbound granular material were assumed to be in an elastic mode. The analysis was conducted for two different AC mixtures in a simplified flexible pavement structure at two different seasons. Finite element analysis results reveal that the loading time has a more pronounced impact on pavement response in the summer for both asphalt types. The results indicate that for reasonable prediction of dynamic response in flexible pavements, the effect of the depth-dependent loading time on pavement temperature should be considered.

Time-response characteristic and potential biomarker identification of heavy metal induced toxicity in zebrafish.

PubMed

Yin, Jian; Wang, Ai-Ping; Li, Wan-Fang; Shi, Rui; Jin, Hong-Tao; Wei, Jin-Feng

2018-01-01

The present work aims to explore the time-response (from 24 h to 96 h) characteristic and identify early potential sensitive biomarkers of copper (Cu) (as copper chloride dihydrate), cadmium (Cd) (as cadmium acetate), lead (Pb) (as lead nitrate) and chromium (Cr) (as potassium dichromate) exposure in adult zebrafish, focusing on reactive oxygen species (ROS), SOD activity, lipid peroxidation and gene expression related to oxidative stress and inflammatory response. Furthermore, the survival rate decreased apparently by a concentration-dependent manner after Cu, Cr, Cd and Pb exposure, and we selected non-lethal concentrations 0.05 mg/L for Cu, 15 mg/L for Cr, 3 mg/L for Cd and 93.75μg/L for Pb to test the effect on the following biological indicators. Under non-lethal concentration, the four heavy metals have no apparent histological change in adult zebrafish gills. Similar trends in ROS production, MDA level and SOD activity were up-regulated by the four heavy metals, while MDA level responded more sensitive to Pb by time-dependent manner than the other three heavy metals. In addition, mRNA levels related to antioxidant system (SOD1, SOD2 and Nrf2) were up-regulated by non-lethal concentration Cu, Cr, Cd and Pb exposure. MDA level and SOD1 gene have a more delayed response to heavy metals. Genes related to immunotoxicity were increased significantly after heavy metals exposure at non-lethal concentrations. TNF-α and IL-1β gene have similar sensibility to the four heavy metals, while IL-8 gene was more responsive to Cr, Cd and Pb exposure at 48 h groups and IFN-γ gene showed more sensitivity to Cu at 48 h groups than the other heavy metals. In conclusion, the present works have suggested that the IFN-γ gene may applied as early sensitive biomarker to identify Cu-induced toxicity, while MDA content and IL-8 gene may use as early sensitive biomarkers for evaluating the risk of Pb exposure. Moreover, IL-8 and IFN-γ gene were more responsive to heavy metals, which may become early sensitive and potential biomarkers for evaluating inflammatory response induced by heavy metals. This work reinforces the concept of the usefulness of gene expression assays in the evaluation of chemicals effects and helps to establish a background data as well as contributes to evaluate early environmental risk for chemicals, even predicting toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inoculum size-dependent interactive regulation of metabolism and stress response of Saccharomyces cerevisiae revealed by comparative metabolomics.

PubMed

Ding, Ming-Zhu; Tian, Hong-Chi; Cheng, Jing-Sheng; Yuan, Ying-Jin

2009-12-01

To investigate the metabolic regulation against inoculum density and stress response to high cell density, comparative metabolomic analysis was employed on Saccharomyces cerevisiae under fermentations with five different inoculum sizes by gas chromatography time-of-flight mass spectrometry. Samples from these fermentations were clearly distinguished by principal components analysis, indicating that inoculum size had a profound effect on the metabolism of S. cerevisiae. Potential biomarkers responsible for the discrimination were identified as glycerol, phosphoric acid, succinate, glycine, isoleucine, proline, palmitoleic acid, myo-inositol and ethanolamine. It indicated that enhanced stress protectants in glycerol biosynthesis and amino acid metabolism, depressed citric acid cycle intermediates, as well as decreased metabolites relating to membrane structure and function were involved as the inoculum size of yeast increased. Furthermore, significantly higher levels of glycerol and proline in yeast cells of higher inoculum size fermentation (40 g l(-1)) revealed that they played important roles in protecting yeast from stresses in high cell density fermentation. These findings provided new insights into characterizing the metabolic regulation and stress response depending on inoculum density during ethanol fermentation.

Time-dependent i-DFT exchange-correlation potentials with memory: applications to the out-of-equilibrium Anderson model

NASA Astrophysics Data System (ADS)

Kurth, Stefan; Stefanucci, Gianluca

2018-06-01

We have recently put forward a steady-state density functional theory (i-DFT) to calculate the transport coefficients of quantum junctions. Within i-DFT it is possible to obtain the steady density on and the steady current through an interacting junction using a fictitious noninteracting junction subject to an effective gate and bias potential. In this work we extend i-DFT to the time domain for the single-impurity Anderson model. By a reverse engineering procedure we extract the exchange-correlation (xc) potential and xc bias at temperatures above the Kondo temperature T K. The derivation is based on a generalization of a recent paper by Dittmann et al. [N. Dittmann et al., Phys. Rev. Lett. 120, 157701 (2018)]. Interestingly the time-dependent (TD) i-DFT potentials depend on the system's history only through the first time-derivative of the density. We perform numerical simulations of the early transient current and investigate the role of the history dependence. We also empirically extend the history-dependent TD i-DFT potentials to temperatures below T K. For this purpose we use a recently proposed parametrization of the i-DFT potentials which yields highly accurate results in the steady state.

Barley (Hordeum vulgare) circadian clock genes can respond rapidly to temperature in an EARLY FLOWERING 3-dependent manner

PubMed Central

Ford, Brett; Deng, Weiwei; Clausen, Jenni; Oliver, Sandra; Boden, Scott; Hemming, Megan; Trevaskis, Ben

2016-01-01

An increase in global temperatures will impact future crop yields. In the cereal crops wheat and barley, high temperatures accelerate reproductive development, reducing the number of grains per plant and final grain yield. Despite this relationship between temperature and cereal yield, it is not clear what genes and molecular pathways mediate the developmental response to increased temperatures. The plant circadian clock can respond to changes in temperature and is important for photoperiod-dependent flowering, and so is a potential mechanism controlling temperature responses in cereal crops. This study examines the relationship between temperature, the circadian clock, and the expression of flowering-time genes in barley (Hordeum vulgare), a crop model for temperate cereals. Transcript levels of barley core circadian clock genes were assayed over a range of temperatures. Transcript levels of core clock genes CCA1, GI, PRR59, PRR73, PRR95, and LUX are increased at higher temperatures. CCA1 and PRR73 respond rapidly to a decrease in temperature whereas GI and PRR59 respond rapidly to an increase in temperature. The response of GI and the PRR genes to changes in temperature is lost in the elf3 mutant indicating that their response to temperature may be dependent on a functional ELF3 gene. PMID:27580625

Timing-dependent LTP and LTD in mouse primary visual cortex following different visual deprivation models

PubMed Central

Chen, Xia; Fu, Junhong; Cheng, Wenbo; Song, Desheng; Qu, Xiaolei; Yang, Zhuo; Zhao, Kanxing

2017-01-01

Visual deprivation during the critical period induces long-lasting changes in cortical circuitry by adaptively modifying neuro-transmission and synaptic connectivity at synapses. Spike timing-dependent plasticity (STDP) is considered a strong candidate for experience-dependent changes. However, the visual deprivation forms that affect timing-dependent long-term potentiation(LTP) and long-term depression(LTD) remain unclear. Here, we demonstrated the temporal window changes of tLTP and tLTD, elicited by coincidental pre- and post-synaptic firing, following different modes of 6-day visual deprivation. Markedly broader temporal windows were found in robust tLTP and tLTD in the V1M of the deprived visual cortex in mice after 6-day MD and DE. The underlying mechanism for the changes seen with visual deprivation in juvenile mice using 6 days of dark exposure or monocular lid suture involves an increased fraction of NR2b-containing NMDAR and the consequent prolongation of NMDAR-mediated response duration. Moreover, a decrease in NR2A protein expression at the synapse is attributable to the reduction of the NR2A/2B ratio in the deprived cortex. PMID:28520739

Intratracheal instillation of single-wall carbon nanotubes in the rat lung induces time-dependent changes in gene expression

PubMed Central

Fujita, Katsuhide; Fukuda, Makiko; Fukui, Hiroko; Horie, Masanori; Endoh, Shigehisa; Uchida, Kunio; Shichiri, Mototada; Morimoto, Yasuo; Ogami, Akira; Iwahashi, Hitoshi

2015-01-01

Abstract The use of carbon nanotubes in the industry has grown; however, little is known about their toxicological mechanism of action. Single-wall carbon nanotube (SWCNT) suspensions were administered by single intratracheal instillation in rats. Persistence of alveolar macrophage-containing granuloma was observed around the sites of SWCNT aggregation at 90 days post-instillation in 0.2-mg- or 0.4-mg-injected doses per rat. Meanwhile, gene expression profiling revealed that a large number of genes involved in the inflammatory response were markedly upregulated until 90 days or 180 days post-instillation. Subsequently, gene expression patterns were dramatically altered at 365 days post-instillation, and the number of upregulated genes involved in the inflammatory response was reduced. These results suggested that alveolar macrophage-containing granuloma reflected a characteristic of the histopathological transition period from the acute-phase to the subchronic-phase of inflammation, as well as pulmonary acute phase response persistence up to 90 or 180 days after intratracheal instillation in this experimental setting. The expression levels of the genes Ctsk, Gcgr, Gpnmb, Lilrb4, Marco, Mreg, Mt3, Padi1, Slc26a4, Spp1, Tnfsf4 and Trem2 were persistently upregulated in a dose-dependent manner until 365 days post-instillation. In addition, the expression levels of Atp6v0d2, Lpo, Mmp7, Mmp12 and Rnase9 were significantly upregulated until 754 days post-instillation. We propose that these persistently upregulated genes in the chronic-phase response following the acute-phase response act as potential biomarkers in lung tissue after SWCNT instillation. This study provides further insight into the time-dependent changes in genomic expression associated with the pulmonary toxicity of SWCNTs. PMID:24911292

Auditory cortical plasticity induced by intracortical microstimulation under pharmacological blockage of inhibitory synapses.

PubMed

Yokota, R; Takahashi, H; Funamizu, A; Uchihara, M; Suzurikawa, J; Kanzaki, R

2006-01-01

Electrical stimulation that can reorganize our neural system has a potential for promising neurorehabilitation. We previously demonstrated that temporally controlled intracortical microstimulation (ICMS) could induce the spike time-dependant plasticity and modify tuning properties of cortical neurons as desired. A 'pairing' ICMS following tone-induced excitatory post-synaptic potentials (EPSPs) produced potentiation in response to the paired tones, while an 'anti-pairing' ICMS preceding the tone-induced EPSPs resulted in depression. However, the conventional ICMS affected both excitatory and inhibitory synapses, and thereby could not quantify net excitatory synaptic effects. In the present work, we evaluated the ICMS effects under a pharmacological blockage of inhibitory inputs. The pharmacological blockage enhanced the ICMS effects, suggesting that inhibitory inputs determine a plastic degree of the neural system. Alternatively, the conventional ICMS had an inadequate timing to control excitatory synaptic inputs, because inhibitory synapse determined the latency of total neural inputs.

Excitation of collective modes in a quantum flute

NASA Astrophysics Data System (ADS)

Torfason, Kristinn; Manolescu, Andrei; Molodoveanu, Valeriu; Gudmundsson, Vidar

2012-06-01

We use a generalized master equation (GME) formalism to describe the nonequilibrium time-dependent transport of Coulomb interacting electrons through a short quantum wire connected to semi-infinite biased leads. The contact strength between the leads and the wire is modulated by out-of-phase time-dependent potentials that simulate a turnstile device. We explore this setup by keeping the contact with one lead at a fixed location at one end of the wire, whereas the contact with the other lead is placed on various sites along the length of the wire. We study the propagation of sinusoidal and rectangular pulses. We find that the current profiles in both leads depend not only on the shape of the pulses, but also on the position of the second contact. The current reflects standing waves created by the contact potentials, like in a wind musical instrument (for example, a flute), but occurring on the background of the equilibrium charge distribution. The number of electrons in our quantum “flute” device varies between two and three. We find that for rectangular pulses the currents in the leads may flow against the bias for short time intervals, due to the higher harmonics of the charge response. The GME is solved numerically in small time steps without resorting to the traditional Markov and rotating wave approximations. The Coulomb interaction between the electrons in the sample is included via the exact diagonalization method. The system (leads plus sample wire) is described by a lattice model.

Electrophysiology of the mammillary complex in vitro. II. Medial mammillary neurons

NASA Technical Reports Server (NTRS)

Alonso, A.; Llinas, R. R.

1992-01-01

1. The electrophysiological properties of guinea pig medial mammillary body (MMB) neurons were studied using an in vitro slice preparation. 2. The neurons (n = 80) had an average resting potential of -57 +/- 5.5 (SD) mV, an input resistance of 176 +/- 83 M omega, and a spike amplitude of 58 +/- 15.7 mV. Most of the neurons were silent at rest (n = 52), but some fired spontaneous single spikes (n = 16) or spike bursts (n = 14). 3. The main electrophysiological characteristic of MMB neurons was the ability to generate Ca(2+)-dependent regenerative events, which resulted in very robust burst responses. However, this regenerative event was not the same for all neurons, ranging from typical low-threshold Ca2+ spikes (LTSs) to intermediate-threshold plateau potentials (ITPs). 4. The ITPs were distinct from the LTSs in that they lasted > or = 100 ms and were not inactivated at membrane potentials at or positive to -55 mV. 5. Some cells with a prominent ITP and no LTS (n = 36) displayed repetitive, usually rhythmic, bursting (n = 14). This ITP could be powerful enough to maintain rhythmic membrane potential oscillations after pharmacological block of Na+ conductances. 6. A group of 32 MMB neurons displayed complex bursting that was generated by activation of both LTSs and ITPs. This was established on the basis of their distinct time- and voltage-dependent characteristics. In a group of neurons (n = 14), the burst responses were exclusively generated by an LTS; however, a Ca(2+)-dependent plateau potential contributed to the generation of rebound-triggered oscillatory firing. 7. In addition to the Ca(2+)-dependent LTS and/or ITP, MMB neurons always displayed high-threshold Ca2+ spikes after reduction of K+ conductances with tetraethylammonium. 8. MMB neurons display one of the richer varieties of voltage-dependent Ca2+ conductances so far encountered in mammalian CNS. We propose that the very prominent endogenous bursting and oscillatory properties of MB neurons allow this nuclear complex to function as an oscillatory relay for the transmission of low-frequency rhythmic activities throughout the limbic circuit.

Eye movement related brain responses to emotional scenes during free viewing

PubMed Central

Simola, Jaana; Torniainen, Jari; Moisala, Mona; Kivikangas, Markus; Krause, Christina M.

2013-01-01

Emotional stimuli are preferentially processed over neutral stimuli. Previous studies, however, disagree on whether emotional stimuli capture attention preattentively or whether the processing advantage is dependent on allocation of attention. The present study investigated attention and emotion processes by measuring brain responses related to eye movement events while 11 participants viewed images selected from the International Affective Picture System (IAPS). Brain responses to emotional stimuli were compared between serial and parallel presentation. An “emotional” set included one image with high positive or negative valence among neutral images. A “neutral” set comprised four neutral images. The participants were asked to indicate which picture—if any—was emotional and to rate that picture on valence and arousal. In the serial condition, the event-related potentials (ERPs) were time-locked to the stimulus onset. In the parallel condition, the ERPs were time-locked to the first eye entry on an image. The eye movement results showed facilitated processing of emotional, especially unpleasant information. The EEG results in both presentation conditions showed that the LPP (“late positive potential”) amplitudes at 400–500 ms were enlarged for the unpleasant and pleasant pictures as compared to neutral pictures. Moreover, the unpleasant scenes elicited stronger responses than pleasant scenes. The ERP results did not support parafoveal emotional processing, although the eye movement results suggested faster attention capture by emotional stimuli. Our findings, thus, suggested that emotional processing depends on overt attentional resources engaged in the processing of emotional content. The results also indicate that brain responses to emotional images can be analyzed time-locked to eye movement events, although the response amplitudes were larger during serial presentation. PMID:23970856

Saliency Detection as a Reactive Process: Unexpected Sensory Events Evoke Corticomuscular Coupling

PubMed Central

Kilintari, Marina; Srinivasan, Mandayam; Haggard, Patrick

2018-01-01

Survival in a fast-changing environment requires animals not only to detect unexpected sensory events, but also to react. In humans, these salient sensory events generate large electrocortical responses, which have been traditionally interpreted within the sensory domain. Here we describe a basic physiological mechanism coupling saliency-related cortical responses with motor output. In four experiments conducted on 70 healthy participants, we show that salient substartle sensory stimuli modulate isometric force exertion by human participants, and that this modulation is tightly coupled with electrocortical activity elicited by the same stimuli. We obtained four main results. First, the force modulation follows a complex triphasic pattern consisting of alternating decreases and increases of force, time-locked to stimulus onset. Second, this modulation occurs regardless of the sensory modality of the eliciting stimulus. Third, the magnitude of the force modulation is predicted by the amplitude of the electrocortical activity elicited by the same stimuli. Fourth, both neural and motor effects are not reflexive but depend on contextual factors. Together, these results indicate that sudden environmental stimuli have an immediate effect on motor processing, through a tight corticomuscular coupling. These observations suggest that saliency detection is not merely perceptive but reactive, preparing the animal for subsequent appropriate actions. SIGNIFICANCE STATEMENT Salient events occurring in the environment, regardless of their modalities, elicit large electrical brain responses, dominated by a widespread “vertex” negative-positive potential. This response is the largest synchronization of neural activity that can be recorded from a healthy human being. Current interpretations assume that this vertex potential reflects sensory processes. Contrary to this general assumption, we show that the vertex potential is strongly coupled with a modulation of muscular activity that follows the same pattern. Both the vertex potential and its motor effects are not reflexive but strongly depend on contextual factors. These results reconceptualize the significance of these evoked electrocortical responses, suggesting that saliency detection is not merely perceptive but reactive, preparing the animal for subsequent appropriate actions. PMID:29378865

Photoionization of Atoms and Ions: Application of Time-Dependent Response Method within the Density Functional Theory.

DTIC Science & Technology

1987-10-13

AD-A±95 686 PHOTOIONIZATION OF ATOMS AND IONS: APPLICATION OF III TIME-DEPENDENT RESPONSE..(U) NAVAL RESEARCH LAB WASHINGTON DC U GUPTA ET AL. 13 OCT...on revere if ncemy and idmntify by block number) FIELD GROUP SUBGROUP Photoionization Density functional Atoms Time dependent 1 S. (Continue on...reverse if necenary and identify by block numnbw) The photoionization cross-section of several atoms (AT, Xe, Rn, Cs) and ions (Ne-like Ar, H-like and Li

Stokes' theorem, gauge symmetry and the time-dependent Aharonov-Bohm effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macdougall, James, E-mail: jbm34@mail.fresnostate.edu; Singleton, Douglas, E-mail: dougs@csufresno.edu

2014-04-15

Stokes' theorem is investigated in the context of the time-dependent Aharonov-Bohm effect—the two-slit quantum interference experiment with a time varying solenoid between the slits. The time varying solenoid produces an electric field which leads to an additional phase shift which is found to exactly cancel the time-dependent part of the usual magnetic Aharonov-Bohm phase shift. This electric field arises from a combination of a non-single valued scalar potential and/or a 3-vector potential. The gauge transformation which leads to the scalar and 3-vector potentials for the electric field is non-single valued. This feature is connected with the non-simply connected topology ofmore » the Aharonov-Bohm set-up. The non-single valued nature of the gauge transformation function has interesting consequences for the 4-dimensional Stokes' theorem for the time-dependent Aharonov-Bohm effect. An experimental test of these conclusions is proposed.« less

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

PubMed Central

Vugmeyster, Liliya; Ostrovsky, Dmitry

2012-01-01

Temperature-dependence of protein dynamics can provide information on details of the free energy landscape by probing the characteristics of the potential responsible for the fluctuations. We have investigated the temperature-dependence of picosecond to nanosecond backbone dynamics at carbonyl carbon sites in chicken villin headpiece subdomain protein using a combination of three NMR relaxation rates: 13C′ longitudinal rate, and two cross-correlated rates involving dipolar and chemical shift anisotropy (CSA) relaxation mechanisms, 13C′/13C′−13Cα CSA/dipolar and 13C′/13C′−15N CSA/dipolar. Order parameters have been extracted using the Lipari-Szabo model-free approach assuming a separation of the time scales of internal and molecular motions in the 2–16°C temperature range. There is a gradual deviation from this assumption from lower to higher temperatures, such that above 16°C the separation of the time scales is inconsistent with the experimental data and, thus, the Lipari-Szabo formalism can not be applied. While there are variations among the residues, on the average the order parameters indicate a markedly steeper temperature dependence at backbone carbonyl carbons compared to that probed at amide nitrogens in an earlier study. This strongly advocates for probing sites other than amide nitrogen for accurate characterization of the potential and other thermodynamics characteristics of protein backbone. PMID:21416162

Time Dependent Behavior of Light Emitting Polymers for Potential Individual Identify Friend or Foe (IIFF) Applications

DTIC Science & Technology

2007-12-01

efficiently it combines electrons and holes, so by testing several different LEP types the one device that provides optimum intensity for the longest period...least voltage for turn on can be determined. The goal of this work was to explore the various relationships between driving current, response voltage...and intensity over the multiple timescales of interest (days, hours and seconds). The relationship between short term activations and long term

Time-evolving collagen-like structural fibers in soft tissues: biaxial loading and spherical inflation

NASA Astrophysics Data System (ADS)

Topol, Heiko; Demirkoparan, Hasan; Pence, Thomas J.; Wineman, Alan

2017-02-01

This work considers a previously developed constitutive theory for the time dependent mechanical response of fibrous soft tissue resulting from the time dependent remodeling of a collagen fiber network that is embedded in a ground substance matrix. The matrix is taken to be an incompressible nonlinear elastic solid. The remodeling process consists of the continual dissolution of existing fibers and the creation of new fibers. Motivated by experimental reports on the enzyme degradation of collagen fibers, the remodeling is governed by first order chemical kinetics such that the dissolution rate is dependent upon the fiber stretch. The resulting time dependent mechanical response is sensitive to the natural configuration of the fibers when they are created, and different assumptions on the nature of the fiber's stress free state are considered here. The response under biaxial loading, a type of loading that has particular significance for the characterization of biological materials, is studied. The inflation of a spherical membrane is then analyzed in terms of the equal biaxial stretch that occurs in the membrane approximation. Different assumptions on the natural configuration of the fibers, combined with their time dependent dissolution and reforming, are shown to emulate alternative forms of creep and relaxation response. This formal similarity to viscoelastic phenomena occurs even though the underlying mechanisms are fundamentally different from the mechanism of macromolecular reconfiguration that one typically associates with viscoelastic response.

Classical Optimal Control for Energy Minimization Based On Diffeomorphic Modulation under Observable-Response-Preserving Homotopy.

PubMed

Soley, Micheline B; Markmann, Andreas; Batista, Victor S

2018-06-12

We introduce the so-called "Classical Optimal Control Optimization" (COCO) method for global energy minimization based on the implementation of the diffeomorphic modulation under observable-response-preserving homotopy (DMORPH) gradient algorithm. A probe particle with time-dependent mass m( t;β) and dipole μ( r, t;β) is evolved classically on the potential energy surface V( r) coupled to an electric field E( t;β), as described by the time-dependent density of states represented on a grid, or otherwise as a linear combination of Gaussians generated by the k-means clustering algorithm. Control parameters β defining m( t;β), μ( r, t;β), and E( t;β) are optimized by following the gradients of the energy with respect to β, adapting them to steer the particle toward the global minimum energy configuration. We find that the resulting COCO algorithm is capable of resolving near-degenerate states separated by large energy barriers and successfully locates the global minima of golf potentials on flat and rugged surfaces, previously explored for testing quantum annealing methodologies and the quantum optimal control optimization (QuOCO) method. Preliminary results show successful energy minimization of multidimensional Lennard-Jones clusters. Beyond the analysis of energy minimization in the specific model systems investigated, we anticipate COCO should be valuable for solving minimization problems in general, including optimization of parameters in applications to machine learning and molecular structure determination.

Properties of visual evoked potentials to onset of movement on a television screen.

PubMed

Kubová, Z; Kuba, M; Hubacek, J; Vít, F

1990-08-01

In 80 subjects the dependence of movement-onset visual evoked potentials on some measures of stimulation was examined, and these responses were compared with pattern-reversal visual evoked potentials to verify the effectiveness of pattern movement application for visual evoked potential acquisition. Horizontally moving vertical gratings were generated on a television screen. The typical movement-onset reactions were characterized by one marked negative peak only, with a peak time between 140 and 200 ms. In all subjects the sufficient stimulus duration for acquisition of movement-onset-related visual evoked potentials was 100 ms; in some cases it was only 20 ms. Higher velocity (5.6 degree/s) produced higher amplitudes of movement-onset visual evoked potentials than did the lower velocity (2.8 degrees/s). In 80% of subjects, the more distinct reactions were found in the leads from lateral occipital areas (in 60% from the right hemisphere), with no correlation to handedness of subjects. Unlike pattern-reversal visual evoked potentials, the movement-onset responses tended to be larger to extramacular stimulation (annular target of 5 degrees-9 degrees) than to macular stimulation (circular target of 5 degrees diameter).

Evaluating models of climate and forest vegetation

NASA Technical Reports Server (NTRS)

Clark, James S.

1992-01-01

Understanding how the biosphere may respond to increasing trace gas concentrations in the atmosphere requires models that contain vegetation responses to regional climate. Most of the processes ecologists study in forests, including trophic interactions, nutrient cycling, and disturbance regimes, and vital components of the world economy, such as forest products and agriculture, will be influenced in potentially unexpected ways by changing climate. These vegetation changes affect climate in the following ways: changing C, N, and S pools; trace gases; albedo; and water balance. The complexity of the indirect interactions among variables that depend on climate, together with the range of different space/time scales that best describe these processes, make the problems of modeling and prediction enormously difficult. These problems of predicting vegetation response to climate warming and potential ways of testing model predictions are the subjects of this chapter.

Roles of N-methyl-d-aspartate receptors during the sensory stimulation-evoked field potential responses in mouse cerebellar cortical molecular layer.

PubMed

Xu, Yin-Hua; Zhang, Guang-Jian; Zhao, Jing-Tong; Chu, Chun-Ping; Li, Yu-Zi; Qiu, De-Lai

2017-11-01

The functions of N-methyl-d-aspartate receptors (NMDARs) in cerebellar cortex have been widely studied under in vitro condition, but their roles during the sensory stimulation-evoked responses in the cerebellar cortical molecular layer in living animals are currently unclear. We here investigated the roles of NMDARs during the air-puff stimulation on ipsilateral whisker pad-evoked field potential responses in cerebellar cortical molecular layer in urethane-anesthetized mice by electrophysiological recording and pharmacological methods. Our results showed that cerebellar surface administration of NMDA induced a dose-dependent decrease in amplitude of the facial stimulation-evoked inhibitory responses (P1) in the molecular layer, accompanied with decreases in decay time, half-width and area under curve (AUC) of P1. The IC 50 of NMDA induced inhibition in amplitude of P1 was 46.5μM. In addition, application of NMDA induced significant increases in the decay time, half-width and AUC values of the facial stimulation-evoked excitatory responses (N1) in the molecular layer. Application of an NMDAR blocker, D-APV (250μM) abolished the facial stimulation-evoked P1 in the molecular layer. These results suggested that NMDARs play a critical role during the sensory information processing in cerebellar cortical molecular layer in vivo in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

A proteorhodopsin-based biohybrid light-powering pH sensor.

PubMed

Rao, Siyuan; Guo, Zhibin; Liang, Dawei; Chen, Deliang; Wei, Yen; Xiang, Yan

2013-10-14

The biohybrid sensor is an emerging technique for multi-functional detection that utilizes the instinctive responses or interactions of biomolecules. We develop a biohybrid pH sensor by taking advantage of the pH-dependent photoelectric characteristics of proteorhodopsin (pR). The transient absorption kinetics study indicates that the photoelectric behavior of pR is attributed to the varying lifetime of the M intermediate at different environmental pH values. This pR-based biohybrid light-powering sensor with microfluidic design can achieve real-time pH detection with quick response and high sensitivity. The results of this work would shed light on pR and its potential applications.

Fast photo-induced color changes of Ag particles deposited on single-crystalline TiO2 surface

NASA Astrophysics Data System (ADS)

Bai, Y. J.; Liu, W. Z.; Chen, A.; Shi, L.; Liu, X. H.; Zi, J.

2018-05-01

It is well known that surface-plasmon enhanced photo-electrochemical effect or photo-thermal effect of metallic particles on a semiconductor substrate or in a suspension may result in color changes. Such character could be potentially applicable to colorimetric sensors, optical filters, and data storage devices. However, usually the response time for color changes is too long to be practically applied. In this letter, we found that the response rate of color changes could be controlled by the annealing condition of the semiconductor substrate, and changes larger than 10% in spectra were observed after only 1-min exposure to light. Furthermore, such fast response was applied to realize wavelength-dependent "write" and "read" applications with high spatial resolution.

Optical response tuning in nanorod-on-semicontinous film systems: A computational study

NASA Astrophysics Data System (ADS)

Mokkath, Junais Habeeb

2018-01-01

Strongly confined and intense optical fields within the plasmonic metal nanocavities show outstanding potential for a wide range of functionalities in nanophotonics. Using time dependent density functional theory calculations, we investigate the optical response evolution as a function of the gap separation distances in nanorod-on-film systems comprised of a nanorod (NR) made of Al or Na on top of an Al film. Huge optical field modulations emerged in the chemically distinct Na NR - Al film system in comparison to the Al NR - Al film system, indicating the vital role of metals involved. We further study the optical response modifications by placing a conducting molecule in the gap region, finding strong spectral modulations via through-molecule electron tunneling.

Temperature dependent evolution of wrinkled single-crystal silicon ribbons on shape memory polymers.

PubMed

Wang, Yu; Yu, Kai; Qi, H Jerry; Xiao, Jianliang

2017-10-25

Shape memory polymers (SMPs) can remember two or more distinct shapes, and thus can have a lot of potential applications. This paper presents combined experimental and theoretical studies on the wrinkling of single-crystal Si ribbons on SMPs and the temperature dependent evolution. Using the shape memory effect of heat responsive SMPs, this study provides a method to build wavy forms of single-crystal silicon thin films on top of SMP substrates. Silicon ribbons obtained from a Si-on-insulator (SOI) wafer are released and transferred onto the surface of programmed SMPs. Then such bilayer systems are recovered at different temperatures, yielding well-defined, wavy profiles of Si ribbons. The wavy profiles are shown to evolve with time, and the evolution behavior strongly depends on the recovery temperature. At relatively low recovery temperatures, both wrinkle wavelength and amplitude increase with time as evolution progresses. Finite element analysis (FEA) accounting for the thermomechanical behavior of SMPs is conducted to study the wrinkling of Si ribbons on SMPs, which shows good agreement with experiment. Merging of wrinkles is observed in FEA, which could explain the increase of wrinkle wavelength observed in the experiment. This study can have important implications for smart stretchable electronics, wrinkling mechanics, stimuli-responsive surface engineering, and advanced manufacturing.

Dose- and time-dependent expression of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (ARNT) in PCB-, B[a]P-, and TBT-exposed intertidal copepod Tigriopus japonicus.

PubMed

Kim, Bo-Mi; Rhee, Jae-Sung; Hwang, Un-Ki; Seo, Jung Soo; Shin, Kyung-Hoon; Lee, Jae-Seong

2015-02-01

The aryl hydrocarbon receptor (AhR) and aryl hydrocarbon nuclear translocator (ARNT) genes from the copepod Tigriopus japonicus (Tj) were cloned to examine their potential functions in the invertebrate putative AhR-CYP signaling pathway. The amino acid sequences encoded by the Tj-AhR and Tj-ARNT genes showed high similarity to homologs of Daphnia and Drosophila, ranging from 68% and 70% similarity for the AhR genes to 56% for the ARNT genes. To determine whether Tj-AhR and Tj-ARNT are modulated by environmental pollutants, transcriptional expression of Tj-AhR and Tj-ARNT was analyzed in response to exposure to five concentrations of polychlorinated biphenyl (PCB 126) (control, 10, 50, 100, 500 μg L(-1)), benzo[a]pyrene (B[a]P) (control, 5, 10, 50, 100 μg L(-1)), and tributyltin (TBT) (control, 1, 5, 10, 20 μg L(-1)) 24h after exposure. A time-course experiment (0, 3, 6, 12, 24h) was performed to analyze mRNA expression patterns after exposure to PCB, B[a]P, and TBT. T. japonicus exhibited dose-dependent and time-dependent upregulation of Tj-AhR and Tj-ARNT in response to pollutant exposure, and the degree of expression was dependent on the pollutant, suggesting that pollutants such as PCB, B[a]P, and TBT modulate expression of Tj-AhR and Tj-ARNT genes in the putative AhR-CYP signaling pathway. Copyright © 2014 Elsevier Ltd. All rights reserved.

Current progress of immunoinformatics approach harnessed for cellular- and antibody-dependent vaccine design.

PubMed

Kazi, Ada; Chuah, Candy; Majeed, Abu Bakar Abdul; Leow, Chiuan Herng; Lim, Boon Huat; Leow, Chiuan Yee

2018-03-12

Immunoinformatics plays a pivotal role in vaccine design, immunodiagnostic development, and antibody production. In the past, antibody design and vaccine development depended exclusively on immunological experiments which are relatively expensive and time-consuming. However, recent advances in the field of immunological bioinformatics have provided feasible tools which can be used to lessen the time and cost required for vaccine and antibody development. This approach allows the selection of immunogenic regions from the pathogen genomes. The ideal regions could be developed as potential vaccine candidates to trigger protective immune responses in the hosts. At present, epitope-based vaccines are attractive concepts which have been successfully trailed to develop vaccines which target rapidly mutating pathogens. In this article, we provide an overview of the current progress of immunoinformatics and their applications in the vaccine design, immune system modeling and therapeutics.

Spike-Timing Dependent Plasticity in Unipolar Silicon Oxide RRAM Devices

PubMed Central

Zarudnyi, Konstantin; Mehonic, Adnan; Montesi, Luca; Buckwell, Mark; Hudziak, Stephen; Kenyon, Anthony J.

2018-01-01

Resistance switching, or Resistive RAM (RRAM) devices show considerable potential for application in hardware spiking neural networks (neuro-inspired computing) by mimicking some of the behavior of biological synapses, and hence enabling non-von Neumann computer architectures. Spike-timing dependent plasticity (STDP) is one such behavior, and one example of several classes of plasticity that are being examined with the aim of finding suitable algorithms for application in many computing tasks such as coincidence detection, classification and image recognition. In previous work we have demonstrated that the neuromorphic capabilities of silicon-rich silicon oxide (SiOx) resistance switching devices extend beyond plasticity to include thresholding, spiking, and integration. We previously demonstrated such behaviors in devices operated in the unipolar mode, opening up the question of whether we could add plasticity to the list of features exhibited by our devices. Here we demonstrate clear STDP in unipolar devices. Significantly, we show that the response of our devices is broadly similar to that of biological synapses. This work further reinforces the potential of simple two-terminal RRAM devices to mimic neuronal functionality in hardware spiking neural networks. PMID:29472837

Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo

PubMed Central

Posfai, Eszter; Petropoulos, Sophie; de Barros, Flavia Regina Oliveira; Schell, John Paul; Jurisica, Igor; Sandberg, Rickard; Lanner, Fredrik; Rossant, Janet

2017-01-01

The segregation of the trophectoderm (TE) from the inner cell mass (ICM) in the mouse blastocyst is determined by position-dependent Hippo signaling. However, the window of responsiveness to Hippo signaling, the exact timing of lineage commitment and the overall relationship between cell commitment and global gene expression changes are still unclear. Single-cell RNA sequencing during lineage segregation revealed that the TE transcriptional profile stabilizes earlier than the ICM and prior to blastocyst formation. Using quantitative Cdx2-eGFP expression as a readout of Hippo signaling activity, we assessed the experimental potential of individual blastomeres based on their level of Cdx2-eGFP expression and correlated potential with gene expression dynamics. We find that TE specification and commitment coincide and occur at the time of transcriptional stabilization, whereas ICM cells still retain the ability to regenerate TE up to the early blastocyst stage. Plasticity of both lineages is coincident with their window of sensitivity to Hippo signaling. DOI: http://dx.doi.org/10.7554/eLife.22906.001 PMID:28226240

(S)-[6]-Gingerol enhances glucose uptake in L6 myotubes by activation of AMPK in response to [Ca2+]i.

PubMed

Li, Yiming; Tran, Van H; Koolaji, Nooshin; Duke, Colin; Roufogalis, Basil D

2013-01-01

The aim of this study was to investigate the mechanism of (S)-[6]-gingerol in promoting glucose uptake in L6 skeletal muscle cells. The effect of (S)-[6]-gingerol on glucose uptake in L6 myotubes was examined using 2-[1,2-3H]-deoxy-D-glucose. Intracellular Ca2+ concentration was measured using Fluo-4. Phosphorylation of AMPKα was determined by Western blotting analysis. (S)-[6]-Gingerol time-dependently enhanced glucose uptake in L6 myotubes. (S)-[6]-Gingerol elevated intracellular Ca2+ concentration and subsequently induced a dose- and time-dependent enhancement of threonine172 phosphorylated AMPKα in L6 myotubes via modulation by Ca2+/calmodulin-dependent protein kinase kinase. The results indicated that (S)-[6]-gingerol increased glucose uptake in L6 skeletal muscle cells by activating AMPK. (S)-[6]-gingerol, a major component of Zingiber officinale, may have potential for development as an antidiabetic agent.

Theory for source-responsive and free-surface film modeling of unsaturated flow

USGS Publications Warehouse

Nimmo, J.R.

2010-01-01

A new model explicitly incorporates the possibility of rapid response, across significant distance, to substantial water input. It is useful for unsaturated flow processes that are not inherently diffusive, or that do not progress through a series of equilibrium states. The term source-responsive is used to mean that flow responds sensitively to changing conditions at the source of water input (e.g., rainfall, irrigation, or ponded infiltration). The domain of preferential flow can be conceptualized as laminar flow in free-surface films along the walls of pores. These films may be considered to have uniform thickness, as suggested by field evidence that preferential flow moves at an approximately uniform rate when generated by a continuous and ample water supply. An effective facial area per unit volume quantitatively characterizes the medium with respect to source-responsive flow. A flow-intensity factor dependent on conditions within the medium represents the amount of source-responsive flow at a given time and position. Laminar flow theory provides relations for the velocity and thickness of flowing source-responsive films. Combination with the Darcy-Buckingham law and the continuity equation leads to expressions for both fluxes and dynamic water contents. Where preferential flow is sometimes or always significant, the interactive combination of source-responsive and diffuse flow has the potential to improve prediction of unsaturated-zone fluxes in response to hydraulic inputs and the evolving distribution of soil moisture. Examples for which this approach is efficient and physically plausible include (i) rainstorm-generated rapid fluctuations of a deep water table and (ii) space- and time-dependent soil water content response to infiltration in a macroporous soil. ?? Soil Science Society of America.

A swinging seesaw as a novel model mechanism for time-dependent hormesis under dose-dependent stimulatory and inhibitory effects: A case study on the toxicity of antibacterial chemicals to Aliivibrio fischeri.

PubMed

Sun, Haoyu; Calabrese, Edward J; Zheng, Min; Wang, Dali; Pan, Yongzheng; Lin, Zhifen; Liu, Ying

2018-08-01

Hormesis occurs frequently in broadly ranging biological areas (e.g. plant biology, microbiology, biogerontology), toxicology, pharmacology and medicine. While numerous mechanisms (e.g. receptor and pathway mediated pathway responses) account for stimulatory and inhibitory features of hormetic dose responses, the vast majority emphasizes the inclusion of many doses but only one timepoint or use of a single optimized dose that is assessed over a broad range of timepoints. In this paper, a toxicity study was designed using a large number of properly spaced doses with responses determined over a large number of timepoints, which could help us reveal the underlying mechanism of hormesis. We present the results of a dose-time-response study on hormesis using five antibacterial chemicals on the bioluminescence of Aliivibrio fischeri, measuring expression of protein mRNA based on quorum sensing, simulating bioluminescent reaction and analyzing toxic actions of test chemicals. The findings show dose-time-dependent responses conforming to the hormetic dose-response model, while revealing unique response dynamics between agent induced stimulatory and inhibitory effects within bacterial growth phase dynamics. These dynamic dose-time features reveal a type of biological seesaw model that integrates stimulatory and inhibitory responses within unique growth phase, dose and time features, which has faultlessly explained the time-dependent hormetic phenomenon induced by five antibacterial chemicals (characterized by low-dose stimulation and high-dose inhibition). This study offers advances in understanding cellular dynamics, the biological integration of diverse and opposing responses and their role in evolutionary adaptive strategies to chemicals, which can provide new insight into the mechanistic investigation of hormesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

In vitro α -amylase and α-glucosidase inhibitory potential of Trigonella foenum-graecum leaves extract

PubMed Central

Ganeshpurkar, Aditya; Diwedi, Varsha; Bhardwaj, Yash

2013-01-01

Trigonella foenum-graecum is one of the widely used herbs in food and medicine. The seeds of the plants are investigated for antidiabetic potential; however, no efforts have been done to explore the potential of leaves to modify carbohydrate metabolizing enzymes viz. α-amylase and α-glucosidase. The present work was designed to investigate the inhibitory potential of ethyl acetate and water extract of T. foenum-graecum on enzymes α-amylase and α-glucosidase. Different concentrations of extracts were used to study inhibition of enzymatic activity of α-amylase and α-glucosidase. A dose dependent inhibitory effect on enzymes was observed. The current study, for the first time, revealed α-amylase and α-glucosidase inhibitory potential of T. foenum-graecum and the study could be helpful to isolate and characterize compounds responsible for it. PMID:24049415

Emergencies planning and response: Coupling an exposure model with different atmospheric dispersion models

NASA Astrophysics Data System (ADS)

Sanchez, E. Y.; Colman Lerner, J. E.; Porta, A.; Jacovkis, P. M.

2013-11-01

Information on spatial and time dependent concentration patterns of hazardous substances, as well as on the potential effects on population, is necessary to assist in chemical emergency planning and response. To that end, some models predict transport and dispersion of hazardous substances, and others estimate potential effects upon exposed population. Taken together, both groups constitute a powerful tool to estimate vulnerable regions and to evaluate environmental impact upon affected populations. The development of methodologies and models with direct application to the context in which we live allows us to draft a more clear representation of the risk scenario and, hence, to obtain the adequate tools for an optimal response. By means of the recently developed DDC (Damage Differential Coupling) exposure model, it was possible to optimize, from both the qualitative and the quantitative points of view, the estimation of the population affected by a toxic cloud, because the DDC model has a very good capacity to couple with different atmospheric dispersion models able to provide data over time. In this way, DDC analyzes the different concentration profiles (output from the transport model) associating them with some reference concentration to identify risk zones. In this work we present a disaster scenario in Chicago (USA), by coupling DDC with two transport models of different complexity, showing the close relationship between a representative result and the run time of the models. In the same way, it becomes evident that knowing the time evolution of the toxic cloud and of the affected regions significantly improves the probability of taking the correct decisions on planning and response facing the emergency.

Increased startle potentiation to unpredictable stressors in alcohol dependence: Possible stress neuroadaptation in humans

PubMed Central

Moberg, Christine A.; Bradford, Daniel E.; Kaye, Jesse T.; Curtin, John J.

2017-01-01

Stress plays a key role in addiction etiology and relapse. Rodent models posit that following repeated periods of alcohol and other drug intoxication, compensatory allostatic changes occur in the central nervous system (CNS) circuits involved in behavioral and emotional response to stressors. We examine a predicted manifestation of this neuroadaptation in recently abstinent alcohol dependent humans. Participants completed a translational laboratory task that uses startle potentiation to unpredictable (vs. predictable) stressors implicated in the putative CNS mechanisms that mediate this neuroadaptation. Alcohol dependent participants displayed significantly greater startle potentiation to unpredictable than predictable stressors relative to non-alcoholic controls. The size of this effect covaried with alcohol-related problems and degree of withdrawal syndrome. This supports the rodent model thesis of a sensitized stress response in abstinent alcoholics. However, this effect could also represent pre-morbid risk or mark more severe and/or comorbid psychopathology. Regardless, pharmacotherapy and psychological interventions may target unpredictable stressor response to reduce stress-induced relapse. PMID:28394145

The Use of Inhibitors of Mechanosensitive Ion Channels as Local Inhibitors of Peripheral Pain

DTIC Science & Technology

2015-01-01

in the medical care of soldiers and veterans, whether in acute or chronic injury. Current analgesics, while effective, suffer from a potential for... potential  of ‐60 mV. Panel B is a dose‐response  curve of mechanical sensitivity with increasing depths of penetration producing more current.  Panel C is...emphasizes that the channels couple mechanical stress to membrane  potential  in time dependent ways. Panel D is an IV  curve derived from the cell‐attached

Cortical pyramidal cells as non-linear oscillators: experiment and spike-generation theory.

PubMed

Brumberg, Joshua C; Gutkin, Boris S

2007-09-26

Cortical neurons are capable of generating trains of action potentials in response to current injections. These discharges can take different forms, e.g., repetitive firing that adapts during the period of current injection or bursting behaviors. We have used a combined experimental and computational approach to characterize the dynamics leading to action potential responses in single neurons. Specifically we investigated the origin of complex firing patterns in response to sinusoidal current injections. Using a reduced model, the theta-neuron, alongside recordings from cortical pyramidal cells we show that both real and simulated neurons show phase-locking to sine wave stimuli up to a critical frequency, above which period skipping and 1-to-x phase-locking occurs. The locking behavior follows a complex "devil's staircase" phenomena, where locked modes are interleaved with irregular firing. We further show that the critical frequency depends on the time scale of spike generation and on the level of spike frequency adaptation. These results suggest that phase-locking of neuronal responses to complex input patterns can be explained by basic properties of the spike-generating machinery.

Statistical Analysis of Human Body Movement and Group Interactions in Response to Music

NASA Astrophysics Data System (ADS)

Desmet, Frank; Leman, Marc; Lesaffre, Micheline; de Bruyn, Leen

Quantification of time series that relate to physiological data is challenging for empirical music research. Up to now, most studies have focused on time-dependent responses of individual subjects in controlled environments. However, little is known about time-dependent responses of between-subject interactions in an ecological context. This paper provides new findings on the statistical analysis of group synchronicity in response to musical stimuli. Different statistical techniques were applied to time-dependent data obtained from an experiment on embodied listening in individual and group settings. Analysis of inter group synchronicity are described. Dynamic Time Warping (DTW) and Cross Correlation Function (CCF) were found to be valid methods to estimate group coherence of the resulting movements. It was found that synchronicity of movements between individuals (human-human interactions) increases significantly in the social context. Moreover, Analysis of Variance (ANOVA) revealed that the type of music is the predominant factor in both the individual and the social context.

The fermionic projector in a time-dependent external potential: Mass oscillation property and Hadamard states

NASA Astrophysics Data System (ADS)

Finster, Felix; Murro, Simone; Röken, Christian

2016-07-01

We give a non-perturbative construction of the fermionic projector in Minkowski space coupled to a time-dependent external potential which is smooth and decays faster than quadratically for large times. The weak and strong mass oscillation properties are proven. We show that the integral kernel of the fermionic projector is of the Hadamard form, provided that the time integral of the spatial sup-norm of the potential satisfies a suitable bound. This gives rise to an algebraic quantum field theory of Dirac fields in an external potential with a distinguished pure quasi-free Hadamard state.

The effect of food temperature on postprandial metabolism in albatrosses.

PubMed

Battam, H; Chappell, M A; Buttemer, W A

2008-04-01

Heat generated by the specific dynamic action (SDA) associated with feeding is known to substitute for the thermoregulatory costs of cold-exposed endotherms; however, the effectiveness of this depends on food temperature. When food is cooler than core body temperature, it is warmed by body heat and, consequently, imposes a thermoregulatory challenge to the animal. The degree to which this cost might be ;paid' by SDA depends on the relative timing of food heating and the SDA response. We investigated this phenomenon in two genera of endotherms, Diomedea and Thalassarche albatrosses, by measuring postprandial metabolic rate following ingestion of food at body temperature (40 degrees C) and cooler (0 and 20 degrees C). This permitted us to estimate potential contributions to food warming by SDA-derived heat, and to observe the effect of cold food on metabolic rate. For meal sizes that were approximately 20% of body mass, SDA was 4.22+/-0.37% of assimilated food energy, and potentially contributed 17.9+/-1.0% and 13.2+/-2.2% of the required heating energy of food at 0 degrees C for Diomedea and Thalassarche albatrosses, respectively, and proportionately greater quantities at higher food temperatures. Cold food increased the rate at which postprandial metabolic rate increased to 3.2-4.5 times that associated with food ingested at body temperature. We also found that albatrosses generated heat in excess by more than 50% of the estimated thermostatic heating demand of cold food, a probable consequence of time delays in physiological responses to afferent signals.

Recent Advances in Drug Design and Drug Discovery for Androgen- Dependent Diseases.

PubMed

Cabeza, Marisa; Sánchez-Márquez, Araceli; Garrido, Mariana; Silva, Aylín; Bratoeff, Eugene

2016-01-01

This article summarizes the importance of different targets such as 5α-reductase, 17β-HSD, CYP17A, androgen receptor and protein kinase A for the treatment of prostate cancer and benign prostatic hyperplasia. It is a well known fact that dihydrotestosterone (DHT) is associated with the development of androgen-dependent afflictions. At the present time, several research groups are attempting to develop new steroidal and non-steroidal molecules with the purpose of inhibiting the synthesis and biological response of DHT. This review also discusses the most recent studies reported in the literature that describe the therapeutic potential of novel compounds, as well as the new drugs, principally inhibitors of 5α-reductase.

Phylogenetic conservatism and trait correlates of spring phenological responses to climate change in northeast China.

PubMed

Du, Yanjun; Chen, Jingru; Willis, Charles G; Zhou, Zhiqiang; Liu, Tong; Dai, Wujun; Zhao, Yuan; Ma, Keping

2017-09-01

Climate change has resulted in major changes in plant phenology across the globe that includes leaf-out date and flowering time. The ability of species to respond to climate change, in part, depends on their response to climate as a phenological cue in general. Species that are not phenologically responsive may suffer in the face of continued climate change. Comparative studies of phenology have found phylogeny to be a reliable predictor of mean leaf-out date and flowering time at both the local and global scales. This is less true for flowering time response (i.e., the correlation between phenological timing and climate factors), while no study to date has explored whether the response of leaf-out date to climate factors exhibits phylogenetic signal. We used a 52-year observational phenological dataset for 52 woody species from the Forest Botanical Garden of Heilongjiang Province, China, to test phylogenetic signal in leaf-out date and flowering time, as well as, the response of these two phenological traits to both temperature and winter precipitation. Leaf-out date and flowering time were significantly responsive to temperature for most species, advancing, on average, 3.11 and 2.87 day/°C, respectively. Both leaf-out and flowering, and their responses to temperature exhibited significant phylogenetic signals. The response of leaf-out date to precipitation exhibited no phylogenetic signal, while flowering time response to precipitation did. Native species tended to have a weaker flowering response to temperature than non-native species. Earlier leaf-out species tended to have a greater response to winter precipitation. This study is the first to assess phylogenetic signal of leaf-out response to climate change, which suggests, that climate change has the potential to shape the plant communities, not only through flowering sensitivity, but also through leaf-out sensitivity.

Distinct antibody responses of patients with mild and severe leptospirosis determined by whole proteome microarray analysis

PubMed Central

Lessa-Aquino, Carolina; Lindow, Janet C.; Randall, Arlo; Wunder, Elsio; Pablo, Jozelyn; Nakajima, Rie; Jasinskas, Algis; Cruz, Jaqueline S.; Damião, Alcineia O.; Nery, Nívison; Ribeiro, Guilherme S.; Costa, Federico; Hagan, José E.; Reis, Mitermayer Galvão; Ko, Albert I.; Medeiros, Marco Alberto; Felgner, Philip L.

2017-01-01

Background Leptospirosis is an important zoonotic disease worldwide. Humans usually present a mild non-specific febrile illness, but a proportion of them develop more severe outcomes, such as multi-organ failure, lung hemorrhage and death. Such complications are thought to depend on several factors, including the host immunity. Protective immunity is associated with humoral immune response, but little is known about the immune response mounted during naturally-acquired Leptospira infection. Methods and principal findings Here, we used protein microarray chip to profile the antibody responses of patients with severe and mild leptospirosis against the complete Leptospira interrogans serovar Copenhageni predicted ORFeome. We discovered a limited number of immunodominant antigens, with 36 antigens specific to patients, of which 11 were potential serodiagnostic antigens, identified at acute phase, and 33 were potential subunit vaccine targets, detected after recovery. Moreover, we found distinct antibody profiles in patients with different clinical outcomes: in the severe group, overall IgM responses do not change and IgG responses increase over time, while both IgM and IgG responses remain stable in the mild patient group. Analyses of individual patients’ responses showed that >74% of patients in the severe group had significant IgG increases over time compared to 29% of patients in the mild group. Additionally, 90% of IgM responses did not change over time in the mild group, compared to ~51% in the severe group. Conclusions In the present study, we detected antibody profiles associated with disease severity and speculate that patients with mild disease were protected from severe outcomes due to pre-existing antibodies, while patients with severe leptospirosis demonstrated an antibody profile typical of first exposure. Our findings represent a significant advance in the understanding of the humoral immune response to Leptospira infection, and we have identified new targets for the development of subunit vaccines and diagnostic tests. PMID:28141801

Acute Stress Dysregulates the LPP ERP Response to Emotional Pictures and Impairs Sustained Attention: Time-Sensitive Effects

PubMed Central

Alomari, Rima A.; Fernandez, Mercedes; Banks, Jonathan B.; Acosta, Juliana; Tartar, Jaime L.

2015-01-01

Stress can increase emotional vigilance at the cost of a decrease in attention towards non-emotional stimuli. However, the time-dependent effects of acute stress on emotion processing are uncertain. We tested the effects of acute stress on subsequent emotion processing up to 40 min following an acute stressor. Our measure of emotion processing was the late positive potential (LPP) component of the visual event-related potential (ERP), and our measure of non-emotional attention was the sustained attention to response task (SART). We also measured cortisol levels before and after the socially evaluated cold pressor test (SECPT) induction. We found that the effects of stress on the LPP ERP emotion measure were time sensitive. Specifically, the LPP ERP was only altered in the late time-point (30–40 min post-stress) when cortisol was at its highest level. Here, the LPP no longer discriminated between the emotional and non-emotional picture categories, most likely because neutral pictures were perceived as emotional. Moreover, compared to the non-stress condition, the stress-condition showed impaired performance on the SART. Our results support the idea that a limit in attention resources after an emotional stressor is associated with the brain incorrectly processing non-emotional stimuli as emotional and interferes with sustained attention. PMID:26010485

Acute Stress Dysregulates the LPP ERP Response to Emotional Pictures and Impairs Sustained Attention: Time-Sensitive Effects.

PubMed

Alomari, Rima A; Fernandez, Mercedes; Banks, Jonathan B; Acosta, Juliana; Tartar, Jaime L

2015-05-20

Stress can increase emotional vigilance at the cost of a decrease in attention towards non-emotional stimuli. However, the time-dependent effects of acute stress on emotion processing are uncertain. We tested the effects of acute stress on subsequent emotion processing up to 40 min following an acute stressor. Our measure of emotion processing was the late positive potential (LPP) component of the visual event-related potential (ERP), and our measure of non-emotional attention was the sustained attention to response task (SART). We also measured cortisol levels before and after the socially evaluated cold pressor test (SECPT) induction. We found that the effects of stress on the LPP ERP emotion measure were time sensitive. Specifically, the LPP ERP was only altered in the late time-point (30-40 min post-stress) when cortisol was at its highest level. Here, the LPP no longer discriminated between the emotional and non-emotional picture categories, most likely because neutral pictures were perceived as emotional. Moreover, compared to the non-stress condition, the stress-condition showed impaired performance on the SART. Our results support the idea that a limit in attention resources after an emotional stressor is associated with the brain incorrectly processing non-emotional stimuli as emotional and interferes with sustained attention.

Patterns of Toxoplasma gondii cyst distribution in the forebrain associate with individual variation in predator odor avoidance and anxiety-related behavior in male Long-Evans rats

PubMed Central

Evans, Andrew K.; Strassmann, Patrick S.; Lee, I-Ping; Sapolsky, Robert M.

2014-01-01

Toxoplasma gondii (T. gondii) is one of the world’s most successful brain parasites. T. gondii engages in parasite manipulation of host behavior and infection has been epidemiologically linked to numerous psychiatric disorders. Mechanisms by which T. gondii alters host behavior are not well understood, but neuroanatomical cyst presence and the localized host immune response to cysts are potential candidates. The aim of these studies was to test the hypothesis that T. gondii manipulation of specific host behaviors is dependent on neuroanatomical location of cysts in a time-dependent function post-infection. We examined neuroanatomical cyst distribution (53 forebrain regions) in infected rats after predator odor aversion behavior and anxiety-related behavior in the elevated plus maze and open field arena, across a 6-week time course. In addition, we examined evidence for microglial response to the parasite across the time course. Our findings demonstrate that while cysts are randomly distributed throughout the forebrain, individual variation in cyst localization, beginning 3 weeks post-infection, can explain individual variation in the effects of T. gondii on behavior. Additionally, not all infected rats develop cysts in the forebrain, and attenuation of predator odor aversion and changes in anxiety-related behavior are linked with cyst presence in specific forebrain areas. Finally, the immune response to cysts is striking. These data provide the foundation for testing hypotheses about proximate mechanisms by which T. gondii alters behavior in specific brain regions, including consequences of establishment of a homeostasis between T. gondii and the host immune response. PMID:24269877

Molecular wave function and effective adiabatic potentials calculated by extended multi-configuration time-dependent Hartree-Fock method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kato, Tsuyoshi; Ide, Yoshihiro; Yamanouchi, Kaoru

We first calculate the ground-state molecular wave function of 1D model H{sub 2} molecule by solving the coupled equations of motion formulated in the extended multi-configuration time-dependent Hartree-Fock (MCTDHF) method by the imaginary time propagation. From the comparisons with the results obtained by the Born-Huang (BH) expansion method as well as with the exact wave function, we observe that the memory size required in the extended MCTDHF method is about two orders of magnitude smaller than in the BH expansion method to achieve the same accuracy for the total energy. Second, in order to provide a theoretical means to understandmore » dynamical behavior of the wave function, we propose to define effective adiabatic potential functions and compare them with the conventional adiabatic electronic potentials, although the notion of the adiabatic potentials is not used in the extended MCTDHF approach. From the comparison, we conclude that by calculating the effective potentials we may be able to predict the energy differences among electronic states even for a time-dependent system, e.g., time-dependent excitation energies, which would be difficult to be estimated within the BH expansion approach.« less

The cytokine-dependent MUTZ-3 cell line as an in vitro model for the screening of contact sensitizers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Azam, Philippe; Peiffer, Jean-Luc; Chamousset, Delphine

2006-04-01

Langerhans cells (LC) are key mediators of contact allergenicity in the skin. However, no in vitro methods exist which are based on the activation process of LC to predict the sensitization potential of chemicals. In this study, we have evaluated the performances of MUTZ-3, a cytokine-dependent human monocytic cell line, in its response to sensitizers. First, we compared undifferentiated MUTZ-3 cells with several standard human cells such as THP-1, KG-1, HL-60, K-562, and U-937 in their response to the strong sensitizer DNCB and the irritant SDS by monitoring the expression levels of HLA-DR, CD54, and CD86 by flow cytometry. Onlymore » MUTZ-3 and THP-1 cells show a strong and specific response to sensitizer, while other cell lines showed very variable responses. Then, we tested MUTZ-3 cells against a wider panel of sensitizers and irritants on a broader spectrum of cell surface markers (HLA-DR, CD40, CD54, CD80, CD86, B7-H1, B7-H2, B7-DC). Of these markers, CD86 proved to be the most reliable since it detected all sensitizers, including benzocaine, a classical false negative in local lymph node assay (LLNA) but not irritants. We confirmed the MUTZ-3 response to DNCB by real-time PCR analysis. Taken together, our data suggest that undifferentiated MUTZ-3 cells may represent a valuable in vitro model for the screening of potential sensitizers.« less

Rapid thermal responsive conductive hybrid cryogels with shape memory properties, photothermal properties and pressure dependent conductivity.

PubMed

Deng, Zexing; Guo, Yi; Ma, Peter X; Guo, Baolin

2018-09-15

Stimuli responsive cryogels with multi-functionality have potential application for electrical devices, actuators, sensors and biomedical devices. However, conventional thermal sensitive poly(N-isopropylacrylamide) cryogels show slow temperature response speed and lack of multi-functionality, which greatly limit their practical application. Herein we present conductive fast (2 min for both deswelling and reswelling behavior) thermally responsive poly(N-isopropylacrylamide) cryogels with rapid shape memory properties (3 s for shape recovery), near-infrared (NIR) light sensitivity and pressure dependent conductivity, and further demonstrated their applications as temperature sensitive on-off switch, NIR light sensitive on-off switch, water triggered shape memory on-off switch and pressure dependent device. These cryogels were first prepared in dimethyl sulfoxide below its melting temperature in ice bath and subsequently put into aniline or pyrrole solution to in situ deposition of conducting polyaniline or polypyrrole nanoparticles. The continuous macroporous sponge-like structure provides cryogels with rapid responsivity both in deswelling, reswelling kinetics and good elasticity. After incorporating electrically conductive polyaniline or polypyrrole nanoaggregates, the hybrid cryogels exhibit desirable conductivity, photothermal property, pressure dependent conductivity and good cytocompatibility. These multifunctional hybrid cryogels make them great potential as stimuli responsive electrical device, tissue engineering scaffolds, drug delivery vehicle and electronic skin. Copyright © 2018 Elsevier Inc. All rights reserved.

Multiple anticancer activities of EF24, a novel curcumin analog, on human ovarian carcinoma cells.

PubMed

Tan, Xin; Sidell, Neil; Mancini, Alessandra; Huang, Ruo-Pan; Shenming Wang; Horowitz, Ira R; Liotta, Dennis C; Taylor, Robert N; Wieser, Friedrich

2010-10-01

Curcumin, a component of turmeric, has been reported to exhibit potential antitumor activities. This study assessed the effects of a novel synthetic curcumin analog, EF24, on proliferation, apoptosis, and vascular endothelial growth factor (VEGF) regulation in platinum-sensitive (IGROV1) and platinum-resistant (SK-OV-3) human ovarian cancer cells. EF24 time- and dose-dependently suppressed the growth of both cell lines and synergized with cisplatin to induce apoptosis. Although treatment with EF24 had no significant effect on VEGF messenger RNA (mRNA) expression,VEGF protein secretion into conditioned media was dose-dependently reduced with EF24 demonstrating ∼8-fold greater potency than curcumin (P < .05). EF24 significantly inhibited hydrogen peroxide (H(2)O(2))-induced VEGF expression, as did the phenolic antioxidant tert-butylhydroquinone (t-BHQ). EF24 upregulated cellular antioxidant responses as observed by the suppression of reactive oxygen species (ROS) generation and activation of antioxidant response element (ARE)-dependent gene transcription. Given its high potency, EF24 is an excellent lead candidate for further development as an adjuvant therapeutic agent in preclinical models of ovarian cancer.

Behavioral responses of wolves to roads: scale-dependent ambivalence

PubMed Central

Nelson, Lindsey; Wabakken, Petter; Sand, Håkan; Liberg, Olof

2014-01-01

Throughout their recent recovery in several industrialized countries, large carnivores have had to cope with a changed landscape dominated by human infrastructure. Population growth depends on the ability of individuals to adapt to these changes by making use of new habitat features and at the same time to avoid increased risks of mortality associated with human infrastructure. We analyzed the summer movements of 19 GPS-collared resident wolves (Canis lupus L.) from 14 territories in Scandinavia in relation to roads. We used resource and step selection functions, including >12000 field-checked GPS-positions and 315 kill sites. Wolves displayed ambivalent responses to roads depending on the spatial scale, road type, time of day, behavioral state, and reproductive status. At the site scale (approximately 0.1 km2), they selected for roads when traveling, nearly doubling their travel speed. Breeding wolves moved the fastest. At the patch scale (10 km2), house density rather than road density was a significant negative predictor of wolf patch selection. At the home range scale (approximately 1000 km2), breeding wolves increased gravel road use with increasing road availability, although at a lower rate than expected. Wolves have adapted to use roads for ease of travel, but at the same time developed a cryptic behavior to avoid human encounters. This behavioral plasticity may have been important in allowing the successful recovery of wolf populations in industrialized countries. However, we emphasize the role of roads as a potential cause of increased human-caused mortality. PMID:25419085

Behavioral responses of wolves to roads: scale-dependent ambivalence.

PubMed

Zimmermann, Barbara; Nelson, Lindsey; Wabakken, Petter; Sand, Håkan; Liberg, Olof

2014-11-01

Throughout their recent recovery in several industrialized countries, large carnivores have had to cope with a changed landscape dominated by human infrastructure. Population growth depends on the ability of individuals to adapt to these changes by making use of new habitat features and at the same time to avoid increased risks of mortality associated with human infrastructure. We analyzed the summer movements of 19 GPS-collared resident wolves ( Canis lupus L.) from 14 territories in Scandinavia in relation to roads. We used resource and step selection functions, including >12000 field-checked GPS-positions and 315 kill sites. Wolves displayed ambivalent responses to roads depending on the spatial scale, road type, time of day, behavioral state, and reproductive status. At the site scale (approximately 0.1 km 2 ), they selected for roads when traveling, nearly doubling their travel speed. Breeding wolves moved the fastest. At the patch scale (10 km 2 ), house density rather than road density was a significant negative predictor of wolf patch selection. At the home range scale (approximately 1000 km 2 ), breeding wolves increased gravel road use with increasing road availability, although at a lower rate than expected. Wolves have adapted to use roads for ease of travel, but at the same time developed a cryptic behavior to avoid human encounters. This behavioral plasticity may have been important in allowing the successful recovery of wolf populations in industrialized countries. However, we emphasize the role of roads as a potential cause of increased human-caused mortality.

Mode of treatment governs curcumin response on doxorubicin-induced toxicity in cardiomyoblasts.

PubMed

Jain, Aditi; Rani, Vibha

2018-05-01

Doxorubicin (Dox) is an effective anti-cancer drug with severe reported cardiotoxicity. Cardiovascular risks associated with present cancer therapeutics demand urgent attention. There has been a growing interest in naturally occurring compounds to improve the therapeutic index as well as prevent non-tumour tissues from sustaining chemotherapy-induced damages. In the present study, the effects of curcumin, a polyphenol isolated from Curcuma longa and well known for its anti-oxidative, anti-cancerous and anti-inflammatory properties, was studied in relation to the Dox-induced cardiotoxicity. As literature suggests conflicting role of curcumin in Dox-induced cardiotoxicity, concentration- and time-dependent studies were conducted to study the different curcumin effects. H9C2 cardiomyoblasts were used in the study and cell viability assays were done to study Dox-induced cellular death. Drug uptake assay for Dox was performed followed by cellular growth inhibition analysis by FACS Calibur. Morphological alterations, intracellular ROS levels and mitochondrial integrity were observed by fluorescent-based microscopic studies. Catalases and superoxide dismutase-inbuilt anti-oxidant enzyme activities were studied, and it was observed that Dox-dependent cardiotoxicity occurs through ROS overproduction by exaggerating the inbuilt anti-oxidant mechanism. Expression analysis for cell death and ROS markers-BCl 2 , Bax, SOD, catalase-was investigated by semi-quantitative RT-PCR, and the Dox-induced stress on cardiac cells was confirmed. Initiator and effector caspases activity analysis also confirmed these findings. Our study proposes that curcumin exerts time-dependent responses on Dox-induced cardiotoxicity, where parallel treatment potentiates and pre-treatment suppresses the Dox-induced toxicity in H9C2 cardiomyoblasts. In conclusion, pre-treatment of curcumin suppresses the Dox-induced cardiotoxicity and holds a great potential as future cardio-oncological therapeutics.

Causal Inference for fMRI Time Series Data with Systematic Errors of Measurement in a Balanced On/Off Study of Social Evaluative Threat.

PubMed

Sobel, Michael E; Lindquist, Martin A

2014-07-01

Functional magnetic resonance imaging (fMRI) has facilitated major advances in understanding human brain function. Neuroscientists are interested in using fMRI to study the effects of external stimuli on brain activity and causal relationships among brain regions, but have not stated what is meant by causation or defined the effects they purport to estimate. Building on Rubin's causal model, we construct a framework for causal inference using blood oxygenation level dependent (BOLD) fMRI time series data. In the usual statistical literature on causal inference, potential outcomes, assumed to be measured without systematic error, are used to define unit and average causal effects. However, in general the potential BOLD responses are measured with stimulus dependent systematic error. Thus we define unit and average causal effects that are free of systematic error. In contrast to the usual case of a randomized experiment where adjustment for intermediate outcomes leads to biased estimates of treatment effects (Rosenbaum, 1984), here the failure to adjust for task dependent systematic error leads to biased estimates. We therefore adjust for systematic error using measured "noise covariates" , using a linear mixed model to estimate the effects and the systematic error. Our results are important for neuroscientists, who typically do not adjust for systematic error. They should also prove useful to researchers in other areas where responses are measured with error and in fields where large amounts of data are collected on relatively few subjects. To illustrate our approach, we re-analyze data from a social evaluative threat task, comparing the findings with results that ignore systematic error.

Dose-response relationships between exercise intensity, cravings, and inhibitory control in methamphetamine dependence: An ERPs study.

PubMed

Wang, Dongshi; Zhou, Chenglin; Zhao, Min; Wu, Xueping; Chang, Yu-Kai

2016-04-01

The present study integrated behavioral and neuroelectric approaches for determining the dose-response relationships between exercise intensity and methamphetamine (MA) craving and between exercise intensity and inhibitory control in individuals with MA dependence. Ninety-two individuals with MA dependence were randomly assigned to an exercise group (light, moderate, or vigorous intensity) or to a reading control group. The participants then completed a craving self-report at four time points: before exercise, during exercise, immediately after exercise, and 50 min after exercise. Event-related potentials were also recorded while the participants completed a standard Go/NoGo task and an MA-related Go/NoGo task approximately 20 min after exercise cessation. The reduction in self-reported MA craving scores of the moderate and vigorous intensity groups was greater than that of the light intensity and control groups during acute exercise as well as immediately and 50 min following exercise termination. Additionally, an inverted-U-shaped relationship between exercise intensity and inhibitory control was generally observed for the behavioral and neuroelectric indices, with the moderate intensity group exhibiting shorter Go reaction times, increased NoGo accuracy, and larger NoGo-N2 amplitudes. Acute exercise may provide benefits for MA-associated craving and inhibitory control in MA-dependent individuals, as revealed by behavioral and neuroelectric measures. Moderate-intensity exercise may be associated with more positive effects, providing preliminary evidence for the establishment of an exercise prescription regarding intensity for MA dependence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Training voluntary motor suppression with real-time feedback of motor evoked potentials.

PubMed

Majid, D S Adnan; Lewis, Christina; Aron, Adam R

2015-05-01

Training people to suppress motor representations voluntarily could improve response control. We evaluated a novel training procedure of real-time feedback of motor evoked potentials (MEPs) generated by transcranial magnetic stimulation (TMS) over motor cortex. On each trial, a cue instructed participants to use a mental strategy to suppress a particular finger representation without overt movement. A single pulse of TMS was delivered over motor cortex, and an MEP-derived measure of hand motor excitability was delivered visually to the participant within 500 ms. In experiment 1, we showed that participants learned to reduce the excitability of a particular finger beneath baseline (selective motor suppression) within 30 min of practice. In experiment 2, we performed a double-blind study with 2 training groups (1 with veridical feedback and 1 with matched sham feedback) to show that selective motor suppression depends on the veridical feedback itself. Experiment 3 further demonstrated the importance of veridical feedback by showing that selective motor suppression did not arise from mere mental imagery, even when incentivized with reward. Thus participants can use real-time feedback of TMS-induced MEPs to discover an effective mental strategy for selective motor suppression. This high-temporal-resolution, trial-by-trial-feedback training method could be used to help people better control response tendencies and may serve as a potential therapy for motor disorders such as Tourette's and dystonia. Copyright © 2015 the American Physiological Society.

Ultrafast dynamic response of single-crystal β-HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine)

NASA Astrophysics Data System (ADS)

Zaug, Joseph M.; Austin, Ryan A.; Armstrong, Michael R.; Crowhurst, Jonathan C.; Goldman, Nir; Ferranti, Louis; Saw, Cheng K.; Swan, Raymond A.; Gross, Richard; Fried, Laurence E.

2018-05-01

We report experimental and computational studies of shock wave dynamics in single-crystal β-HMX on an ultrafast time scale. Here, a laser-based compression drive (˜1 ns in duration; stresses of up to ˜40 GPa) is used to propagate shock waves normal to the (110) and (010) lattice planes. Ultrafast time-domain interferometry measurements reveal distinct, time-dependent relationships between the shock wave velocity and particle velocity for each crystal orientation, which suggest evolving physical processes on a sub-nanosecond time scale. To help interpret the experimental data, elastic shock wave response was simulated using a finite-strain model of crystal thermoelasticity. At early propagation times (<500 ps), the model is in agreement with the data, which indicates that the mechanical response is dominated by thermoelastic deformation. The model agreement depends on the inclusion of nonlinear elastic effects in both the spherical and deviatoric stress-strain responses. This is achieved by employing an equation-of-state and a pressure-dependent stiffness tensor, which was computed via atomistic simulation. At later times (>500 ps), the crystal samples exhibit signatures of inelastic deformation, structural phase transformation, or chemical reaction, depending on the direction of wave propagation.

DFT and TD-DFT calculations of metallotetraphenylporphyrin and metallotetraphenylporphyrin fullerene complexes as potential dye sensitizers for solar cells

NASA Astrophysics Data System (ADS)

El Mahdy, A. M.; Halim, Shimaa Abdel; Taha, H. O.

2018-05-01

Density functional theory (DFT) and time-dependent DFT calculations have been employed to model metallotetraphenylporphyrin dyes and metallotetraphenylporphyrin -fullerene complexes in order to investigate the geometries, electronic structures, the density of states, non-linear optical properties (NLO), IR-vis spectra, molecular electrostatic potential contours, and electrophilicity. To calculate the excited states of the tetraphenyl porphyrin analogs, time-dependent density functional theory (TD-DFT) are used. Their UV-vis spectra were also obtained and a comparison with available experimental and theoretical results is included. The results reveal that the metal and the tertiary butyl groups of the dyes are electron donors, and the tetraphenylporphyrin rings are electron acceptors. The HOMOs of the dyes fall within the (TiO2)60 and Ti38O76 band gaps and support the issue of typical interfacial electron transfer reaction. The resulting potential drop of Mn-TPP-C60 increased by ca. 3.50% under the effect of the tertiary butyl groups. The increase in the potential drop indicates that the tertiary butyl complexes could be a better choice for the strong operation of the molecular rectifiers. The introduction of metal atom and tertiary butyl groups to the tetraphenyl porphyrin moiety leads to a stronger response to the external electric field and induces higher photo-to-current conversion efficiency. This also shifts the absorption in the dyes and makes them potential candidates for harvesting light in the entire visible and near IR region for photovoltaic applications.

Some Exact Results for the Schroedinger Wave Equation with a Time Dependent Potential

NASA Technical Reports Server (NTRS)

Campbell, Joel

2009-01-01

The time dependent Schroedinger equation with a time dependent delta function potential is solved exactly for many special cases. In all other cases the problem can be reduced to an integral equation of the Volterra type. It is shown that by knowing the wave function at the origin, one may derive the wave function everywhere. Thus, the problem is reduced from a PDE in two variables to an integral equation in one. These results are used to compare adiabatic versus sudden changes in the potential. It is shown that adiabatic changes in the p otential lead to conservation of the normalization of the probability density.

Redox-dependent spatially resolved electrochemistry at graphene and graphite step edges.

PubMed

Güell, Aleix G; Cuharuc, Anatolii S; Kim, Yang-Rae; Zhang, Guohui; Tan, Sze-yin; Ebejer, Neil; Unwin, Patrick R

2015-04-28

The electrochemical (EC) behavior of mechanically exfoliated graphene and highly oriented pyrolytic graphite (HOPG) is studied at high spatial resolution in aqueous solutions using Ru(NH3)6(3+/2+) as a redox probe whose standard potential sits close to the intrinsic Fermi level of graphene and graphite. When scanning electrochemical cell microscopy (SECCM) data are coupled with that from complementary techniques (AFM, micro-Raman) applied to the same sample area, different time-dependent EC activity between the basal planes and step edges is revealed. In contrast, other redox couples (ferrocene derivatives) whose potential is further removed from the intrinsic Fermi level of graphene and graphite show uniform and high activity (close to diffusion-control). Macroscopic voltammetric measurements in different environments reveal that the time-dependent behavior after HOPG cleavage, peculiar to Ru(NH3)6(3+/2+), is not associated particularly with any surface contaminants but is reasonably attributed to the spontaneous delamination of the HOPG with time to create partially coupled graphene layers, further supported by conductive AFM measurements. This process has a major impact on the density of states of graphene and graphite edges, particularly at the intrinsic Fermi level to which Ru(NH3)6(3+/2+) is most sensitive. Through the use of an improved voltammetric mode of SECCM, we produce movies of potential-resolved and spatially resolved HOPG activity, revealing how enhanced activity at step edges is a subtle effect for Ru(NH3)6(3+/2+). These latter studies allow us to propose a microscopic model to interpret the EC response of graphene (basal plane and edges) and aged HOPG considering the nontrivial electronic band structure.

[Patterns of action potential firing in cortical neurons of neonatal mice and their electrophysiological property].

PubMed

Furong, Liu; Shengtian, L I

2016-05-25

To investigate patterns of action potential firing in cortical heurons of neonatal mice and their electrophysiological properties. The passive and active membrane properties of cortical neurons from 3-d neonatal mice were observed by whole-cell patch clamp with different voltage and current mode. Three patterns of action potential firing were identified in response to depolarized current injection. The effects of action potential firing patterns on voltage-dependent inward and outward current were found. Neurons with three different firing patterns had different thresholds of depolarized current. In the morphology analysis of action potential, the three type neurons were different in rise time, duration, amplitude and threshold of the first action potential evoked by 80 pA current injection. The passive properties were similar in three patterns of action potential firing. These results indicate that newborn cortical neurons exhibit different patterns of action potential firing with different action potential parameters such as shape and threshold.

Vestibular short latency responses to pulsed linear acceleration in unanesthetized animals

NASA Technical Reports Server (NTRS)

Jones, T. A.

1992-01-01

Linear acceleration transients were used to elicit vestibular compound action potentials in non-invasively prepared, unanesthetized animals for the first time (chicks, Gallus domesticus, n = 33). Responses were composed of a series of up to 8 dominant peaks occurring within 8 msec of the stimulus. Response amplitudes for 1.0 g stimulus ranged from 1 to 10 microV. A late, slow, triphasic, anesthesia-labile component was identified as a dominant response feature in unanesthetized animals. Amplitudes increased and latencies decreased as stimulus intensity was increased (MANOVA P less than 0.05). Linear regression slope ranges were: amplitudes = 1.0-5.0 microV/g; latencies = -300 to -1100 microseconds/g. Thresholds for single polarity stimuli (0.035 +/- 0.022 g, n = 11) were significantly lower than those of alternating polarity (0.074 +/- 0.028 g, n = 18, P less than 0.001). Bilateral labyrinthectomy eliminated responses whereas bilateral extirpation of cochleae did not significantly change response thresholds. Intense acoustic masking (100/104 dB SL) produced no effect in 2 animals, but did produce small to moderate effects on response amplitudes in 7 others. Changes were attributed to effects on vestibular end organs. Results of unilateral labyrinth blockade (tetrodotoxin) suggest that P1 and N1 preferentially reflect ipsilateral eighth nerve compound action potentials whereas components beyond approximately 2 msec reflect activity from vestibular neurons that depend on both labyrinths. The results demonstrate that short latency vestibular compound action potentials can be measured in unanesthetized, non-invasively prepared animals.

Direction dependence of displacement time for two-fluid electroosmotic flow.

PubMed

Lim, Chun Yee; Lam, Yee Cheong

2012-03-01

Electroosmotic flow that involves one fluid displacing another fluid is commonly encountered in various microfludic applications and experiments, for example, current monitoring technique to determine zeta potential of microchannel. There is experimentally observed anomaly in such flow, namely, the displacement time is flow direction dependent, i.e., it depends if it is a high concentration fluid displacing a low concentration fluid, or vice versa. Thus, this investigation focuses on the displacement flow of two fluids with various concentration differences. The displacement time was determined experimentally with current monitoring method. It is concluded that the time required for a high concentration solution to displace a low concentration solution is smaller than the time required for a low concentration solution to displace a high concentration solution. The percentage displacement time difference increases with increasing concentration difference and independent of the length or width of the channel and the voltage applied. Hitherto, no theoretical analysis or numerical simulation has been conducted to explain this phenomenon. A numerical model based on finite element method was developed to explain the experimental observations. Simulations showed that the velocity profile and ion distribution deviate significantly from a single fluid electroosmotic flow. The distortion of ion distribution near the electrical double layer is responsible for the displacement time difference for the two different flow directions. The trends obtained from simulations agree with the experimental findings.

Direction dependence of displacement time for two-fluid electroosmotic flow

PubMed Central

Lim, Chun Yee; Lam, Yee Cheong

2012-01-01

Electroosmotic flow that involves one fluid displacing another fluid is commonly encountered in various microfludic applications and experiments, for example, current monitoring technique to determine zeta potential of microchannel. There is experimentally observed anomaly in such flow, namely, the displacement time is flow direction dependent, i.e., it depends if it is a high concentration fluid displacing a low concentration fluid, or vice versa. Thus, this investigation focuses on the displacement flow of two fluids with various concentration differences. The displacement time was determined experimentally with current monitoring method. It is concluded that the time required for a high concentration solution to displace a low concentration solution is smaller than the time required for a low concentration solution to displace a high concentration solution. The percentage displacement time difference increases with increasing concentration difference and independent of the length or width of the channel and the voltage applied. Hitherto, no theoretical analysis or numerical simulation has been conducted to explain this phenomenon. A numerical model based on finite element method was developed to explain the experimental observations. Simulations showed that the velocity profile and ion distribution deviate significantly from a single fluid electroosmotic flow. The distortion of ion distribution near the electrical double layer is responsible for the displacement time difference for the two different flow directions. The trends obtained from simulations agree with the experimental findings. PMID:22662083

Sensory Organ Like Response of Zigzag Edge Graphene Nanoribbons

NASA Astrophysics Data System (ADS)

Shenoy, Vijay; Bhowmick, Somnath

2011-03-01

Using a continuum Dirac theory, we study the density and spin response of zigzag edge terminated graphene ribbons subjected to edge potentials and Zeeman fields. Our analytical calculations of the density and spin responses of the closed system (fixed particle number) to the static edge fields, show a highly nonlinear Weber-Fechner type behavior where the response depends logarithmically on the edge potential. The dependence of the response on the size of the system (e.g.~width of a nanoribbon) is also uncovered. Zigzag edge graphene nanoribbons, therefore, provide a realization of response of organs such as the eye and ear that obey Weber-Fechner law. We validate our analytical results with tight binding calculations. These results are crucial in understanding important effects of electron-electron interactions in graphene nanoribbons such as edge magnetism etc., and also suggest possibilities for device applications of graphene nanoribbons. Work supported by DST, India through MONAMI and Ramanujan grants.

The Polar Ionosphere and Interplanetary Field.

DTIC Science & Technology

1987-08-01

model for investigating time dependent behavior of the Polar F-region ionosphere in response to varying interplanetary magnetic field (IMF...conditions. The model has been used to illustrate ionospheric behavior during geomagnetic storms conditions. Future model applications may include...magnetosphere model for investigating time dependent behavior of the polar F-region ionosphere in response to varying interplanetary magnetic field

Real-time dosimetry in radiotherapy using tailored optical fibers

NASA Astrophysics Data System (ADS)

Rahman, A. K. M. Mizanur; Zubair, H. T.; Begum, Mahfuza; Abdul-Rashid, H. A.; Yusoff, Z.; Omar, Nasr Y. M.; Ung, N. M.; Mat-Sharif, K. A.; Bradley, D. A.

2016-05-01

Real-time dosimetry plays an important role for accurate patient-dose measurement during radiotherapy. A tiny piece of laboratory fabricated Ge-doped optical fiber has been investigated as a radioluminescence (RL) sensor for real-time dosimetry over the dose range from 1 Gy to 8 Gy under 6 MV photon beam by LINAC. Fiber-coupled software-based RL prototype system was used to assess essential dosimetric characteristics including dose response linearity, dose rate dependency, sensitivity, repeatability and output dependence on field sizes. The consistency level of RL photon counts versus dose rate was also compared with that of standard Al2O3:C chips. Sensitivity of Ge-doped fiber were found to be sufficiently sensitive for practical use and also provided linear dose responses for various dose rates from 100 cGy/min to 600 cGy/min using both 6 MV photon and 6 MeV electron beams. SEM-EDX analysis was performed to identify Ge-dopant concentration level within the optical fiber RL material. Accumulated doses were also estimated using simple integral technique and the error was found to be around less than 1% under dissimilar dose rates or repeat measurements. The evaluation of the Ge-doped optical fiber based RL dosimeter system indicates its potential in medical dosimetry.

Time dependent reduction in platelet aggregation using the multiplate analyser and hirudin blood due to platelet clumping.

PubMed

Chapman, Kent; Favaloro, Emmanuel J

2018-05-01

The Multiplate is a popular instrument that measures platelet function using whole blood. Potentially considered a point of care instrument, it is also used by hemostasis laboratories. The instrument is usually utilized to assess antiplatelet medication or as a screen of platelet function. According to the manufacturer, testing should be performed within 0.5-3 hours of blood collection, and preferably using manufacturer provided hirudin tubes. We report time-associated reduction in platelet aggregation using the Multiplate and hirudin blood collection tubes, for all the major employed agonists. Blood for Multiplate analysis was collected into manufacturer supplied hirudin tubes, and 21 consecutive samples assessed using manufacturer supplied agonists (ADP, arachidonic acid, TRAP, collagen and ristocetin), at several time-points post-sample collection within the recommended test time period. Blood was also collected into EDTA as a reference method for platelet counts, with samples collected into sodium citrate and hirudin used for comparative counts. All platelet agonists showed a diminution of response with time. Depending on the agonist, the reduction caused 5-20% and 22-47% of responses initially in the normal reference range to fall below the reference range at 120min and 180min, respectively. Considering any agonist, 35% and 67% of initially "normal" responses became 'abnormal' at 120 min and 180 min, respectively. Platelet counts showed generally minimal changes in EDTA blood, but were markedly reduced over time in both citrate and hirudin blood, with up to 40% and 60% reduction, respectively, at 240 min. The presence of platelet clumping (micro-aggregate formation) was also observed in a time dependent manner, especially for hirudin. In conclusion, considering any platelet agonist, around two-thirds of samples can, within the recommended 0.5-3 hour testing window post-blood collection, yield a reduction in platelet aggregation that may lead to a change in interpretation (i.e., normal to reduced). Thus, the stability of Multiplate testing can more realistically be considered as being between 30-120 min of blood collection for samples collected into hirudin.

Cardiac action potential repolarization revisited: early repolarization shows all-or-none behaviour.

PubMed

Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Noble, Denis; Giles, Wayne

2017-11-01

In healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, AP height and duration are key physiological variables. In addition, rate-dependent changes in ventricular AP duration (APD), and variations in APD at a fixed heart rate are both reliable biomarkers of electrophysiological stability. Present guidelines for the likelihood that candidate drugs will increase arrhythmias rely on small changes in APD and Q-T intervals as criteria for safety pharmacology decisions. However, both of these measurements correspond to the final repolarization of the AP. Emerging clinical evidence draws attention to the early repolarization phase of the action potential (and the J-wave of the ECG) as an additional important biomarker for arrhythmogenesis. Here we provide a mechanistic background to this early repolarization syndrome by summarizing the evidence that both the initial depolarization and repolarization phases of the cardiac action potential can exhibit distinct time- and voltage-dependent thresholds, and also demonstrating that both can show regenerative all-or-none behaviour. An important consequence of this is that not all of the dynamics of action potential repolarization in human ventricle can be captured by data from single myocytes when these results are expressed as 'repolarization reserve'. For example, the complex pattern of cell-to-cell current flow that is responsible for AP conduction (propagation) within the mammalian myocardium can change APD and the Q-T interval of the electrocardiogram alter APD stability, and modulate responsiveness to pharmacological agents (such as Class III anti-arrhythmic drugs). © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Simulating Excitons in MoS2 with Time-Dependent Density Functional Theory

NASA Astrophysics Data System (ADS)

Flamant, Cedric; Kolesov, Grigory; Kaxiras, Efthimios

Monolayer molybdenum disulfide, owing to its graphene-like two-dimensional geometry whilst still having a finite bandgap, is a material of great interest in condensed matter physics and for potential application in electronic devices. In particular, MoS2 exhibits significant excitonic effects, a desirable quality for fundamental many-body research. Time-dependent density functional theory (TD-DFT) allows us to simulate dynamical effects as well as temperature-based effects in a natural way given the direct treatment of the time evolution of the system. We present a TD-DFT study of monolayer MoS2 exciton dynamics, examining various qualitative and quantitative predictions in pure samples and in the presence of defects. In particular, we generate an absorption spectrum through simulated pulse excitation for comparison to experiment and also analyze the response of the exciton in an external electric field.In this work we also discuss the electronic structure of the exciton in MoS2 with and without vacancies.

Watching ultrafast responses of structure and magnetism in condensed matter with momentum-resolved probes

PubMed Central

Johnson, S. L.; Savoini, M.; Beaud, P.; Ingold, G.; Staub, U.; Carbone, F.; Castiglioni, L.; Hengsberger, M.; Osterwalder, J.

2017-01-01

We present a non-comprehensive review of some representative experimental studies in crystalline condensed matter systems where the effects of intense ultrashort light pulses are probed using x-ray diffraction and photoelectron spectroscopy. On an ultrafast (sub-picosecond) time scale, conventional concepts derived from the assumption of thermodynamic equilibrium must often be modified in order to adequately describe the time-dependent changes in material properties. There are several commonly adopted approaches to this modification, appropriate in different experimental circumstances. One approach is to treat the material as a collection of quasi-thermal subsystems in thermal contact with each other in the so-called “N-temperature” models. On the other extreme, one can also treat the time-dependent changes as fully coherent dynamics of a sometimes complex network of excitations. Here, we present examples of experiments that fall into each of these categories, as well as experiments that partake of both models. We conclude with a discussion of the limitations and future potential of these concepts. PMID:29308418

Differential expression of muscarinic acetylcholine receptor subtypes in Jurkat cells and their signaling.

PubMed

Alea, Mileidys Perez; Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Fuxe, Kjell; Garriga, Pere

2011-08-15

Muscarinic acetylcholine receptors expression and signaling in the human Jurkat T cell line were investigated. Semiquantitative real-time PCR and radioligand binding studies, using a wide set of antagonist compounds, showed the co-existence of M(3), M(4), and M(5) subtypes. Stimulation of these subpopulations caused a concentration and time- dependent activation of second messengers and ERK signaling pathways, with a major contribution of the M(3) subtype in a G(q/11)-mediated response. In addition, we found that T-cell stimulation leads to increased expression of M(3) and M(5) both at transcriptional and protein levels in a PLC/PKCθ dependent manner. Our data clarifies the functional role of AChR subtypes in Jurkat cells and pave the way to future studies on the potential cross-talk among these subpopulations and their regulation of T lymphocytes immune function. Copyright © 2011 Elsevier B.V. All rights reserved.

When can the cause of a population decline be determined?

PubMed

Hefley, Trevor J; Hooten, Mevin B; Drake, John M; Russell, Robin E; Walsh, Daniel P

2016-11-01

Inferring the factors responsible for declines in abundance is a prerequisite to preventing the extinction of wild populations. Many of the policies and programmes intended to prevent extinctions operate on the assumption that the factors driving the decline of a population can be determined. Exogenous factors that cause declines in abundance can be statistically confounded with endogenous factors such as density dependence. To demonstrate the potential for confounding, we used an experiment where replicated populations were driven to extinction by gradually manipulating habitat quality. In many of the replicated populations, habitat quality and density dependence were confounded, which obscured causal inference. Our results show that confounding is likely to occur when the exogenous factors that are driving the decline change gradually over time. Our study has direct implications for wild populations, because many factors that could drive a population to extinction change gradually through time. © 2016 John Wiley & Sons Ltd/CNRS.

When can the cause of a population decline be determined?

USGS Publications Warehouse

Hefley, Trevor J.; Hooten, Mevin B.; Drake, John M.; Russell, Robin E.; Walsh, Daniel P.

2016-01-01

Inferring the factors responsible for declines in abundance is a prerequisite to preventing the extinction of wild populations. Many of the policies and programmes intended to prevent extinctions operate on the assumption that the factors driving the decline of a population can be determined. Exogenous factors that cause declines in abundance can be statistically confounded with endogenous factors such as density dependence. To demonstrate the potential for confounding, we used an experiment where replicated populations were driven to extinction by gradually manipulating habitat quality. In many of the replicated populations, habitat quality and density dependence were confounded, which obscured causal inference. Our results show that confounding is likely to occur when the exogenous factors that are driving the decline change gradually over time. Our study has direct implications for wild populations, because many factors that could drive a population to extinction change gradually through time.

Coding and decoding with adapting neurons: a population approach to the peri-stimulus time histogram.

PubMed

Naud, Richard; Gerstner, Wulfram

2012-01-01

The response of a neuron to a time-dependent stimulus, as measured in a Peri-Stimulus-Time-Histogram (PSTH), exhibits an intricate temporal structure that reflects potential temporal coding principles. Here we analyze the encoding and decoding of PSTHs for spiking neurons with arbitrary refractoriness and adaptation. As a modeling framework, we use the spike response model, also known as the generalized linear neuron model. Because of refractoriness, the effect of the most recent spike on the spiking probability a few milliseconds later is very strong. The influence of the last spike needs therefore to be described with high precision, while the rest of the neuronal spiking history merely introduces an average self-inhibition or adaptation that depends on the expected number of past spikes but not on the exact spike timings. Based on these insights, we derive a 'quasi-renewal equation' which is shown to yield an excellent description of the firing rate of adapting neurons. We explore the domain of validity of the quasi-renewal equation and compare it with other rate equations for populations of spiking neurons. The problem of decoding the stimulus from the population response (or PSTH) is addressed analogously. We find that for small levels of activity and weak adaptation, a simple accumulator of the past activity is sufficient to decode the original input, but when refractory effects become large decoding becomes a non-linear function of the past activity. The results presented here can be applied to the mean-field analysis of coupled neuron networks, but also to arbitrary point processes with negative self-interaction.

Communication: Rigorous quantum dynamics of O + O{sub 2} exchange reactions on an ab initio potential energy surface substantiate the negative temperature dependence of rate coefficients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yaqin; Sun, Zhigang, E-mail: zsun@dicp.ac.cn, E-mail: dawesr@mst.edu, E-mail: hguo@unm.edu; Center for Advanced Chemical Physics, University of Science and Technology of China, 96 Jinzhai Road, Hefei 230026

2014-08-28

The kinetics and dynamics of several O + O{sub 2} isotope exchange reactions have been investigated on a recently determined accurate global O{sub 3} potential energy surface using a time-dependent wave packet method. The agreement between calculated and measured rate coefficients is significantly improved over previous work. More importantly, the experimentally observed negative temperature dependence of the rate coefficients is for the first time rigorously reproduced theoretically. This negative temperature dependence can be attributed to the absence in the new potential energy surface of a submerged “reef” structure, which was present in all previous potential energy surfaces. In addition, contributionsmore » of rotational excited states of the diatomic reactant further accentuate the negative temperature dependence.« less

Multi-period response management to contaminated water distribution networks: dynamic programming versus genetic algorithms

NASA Astrophysics Data System (ADS)

Bashi-Azghadi, Seyyed Nasser; Afshar, Abbas; Afshar, Mohammad Hadi

2018-03-01

Previous studies on consequence management assume that the selected response action including valve closure and/or hydrant opening remains unchanged during the entire management period. This study presents a new embedded simulation-optimization methodology for deriving time-varying operational response actions in which the network topology may change from one stage to another. Dynamic programming (DP) and genetic algorithm (GA) are used in order to minimize selected objective functions. Two networks of small and large sizes are used in order to illustrate the performance of the proposed modelling schemes if a time-dependent consequence management strategy is to be implemented. The results show that for a small number of decision variables even in large-scale networks, DP is superior in terms of accuracy and computer runtime. However, as the number of potential actions grows, DP loses its merit over the GA approach. This study clearly proves the priority of the proposed dynamic operation strategy over the commonly used static strategy.

Low threshold optical bistability in one-dimensional gratings based on graphene plasmonics.

PubMed

Guo, Jun; Jiang, Leyong; Jia, Yue; Dai, Xiaoyu; Xiang, Yuanjiang; Fan, Dianyuan

2017-03-20

Optical bistability of graphene surface plasmon is investigated numerically, using grating coupling method at normal light incidence. The linear surface plasmon resonance is strongly dependent on Femi-level of graphene, hence it can be tuned in a large wavelength range. Due to the field enhancement of graphene surface plasmon resonance and large third-order nonlinear response of graphene, a low-threshold optical hysteresis has been observed. The threshold value with 20MW/cm² and response time with 1.7ps have been verified. Especially, it is found that this optical bistability phenomenon is angular insensitivity for near 15° incident angle. The threshold of optical bistability can be further lowered to 0.5MW/cm² by using graphene nanoribbons, and the response time is also shorten to 800fs. We believe that our results will find potential applications in bistable devices and all-optical switching from mid-IR to THz range.

Predicting Spike Occurrence and Neuronal Responsiveness from LFPs in Primary Somatosensory Cortex

PubMed Central

Storchi, Riccardo; Zippo, Antonio G.; Caramenti, Gian Carlo; Valente, Maurizio; Biella, Gabriele E. M.

2012-01-01

Local Field Potentials (LFPs) integrate multiple neuronal events like synaptic inputs and intracellular potentials. LFP spatiotemporal features are particularly relevant in view of their applications both in research (e.g. for understanding brain rhythms, inter-areal neural communication and neronal coding) and in the clinics (e.g. for improving invasive Brain-Machine Interface devices). However the relation between LFPs and spikes is complex and not fully understood. As spikes represent the fundamental currency of neuronal communication this gap in knowledge strongly limits our comprehension of neuronal phenomena underlying LFPs. We investigated the LFP-spike relation during tactile stimulation in primary somatosensory (S-I) cortex in the rat. First we quantified how reliably LFPs and spikes code for a stimulus occurrence. Then we used the information obtained from our analyses to design a predictive model for spike occurrence based on LFP inputs. The model was endowed with a flexible meta-structure whose exact form, both in parameters and structure, was estimated by using a multi-objective optimization strategy. Our method provided a set of nonlinear simple equations that maximized the match between models and true neurons in terms of spike timings and Peri Stimulus Time Histograms. We found that both LFPs and spikes can code for stimulus occurrence with millisecond precision, showing, however, high variability. Spike patterns were predicted significantly above chance for 75% of the neurons analysed. Crucially, the level of prediction accuracy depended on the reliability in coding for the stimulus occurrence. The best predictions were obtained when both spikes and LFPs were highly responsive to the stimuli. Spike reliability is known to depend on neuron intrinsic properties (i.e. on channel noise) and on spontaneous local network fluctuations. Our results suggest that the latter, measured through the LFP response variability, play a dominant role. PMID:22586452

Predicting spike occurrence and neuronal responsiveness from LFPs in primary somatosensory cortex.

PubMed

Storchi, Riccardo; Zippo, Antonio G; Caramenti, Gian Carlo; Valente, Maurizio; Biella, Gabriele E M

2012-01-01

Local Field Potentials (LFPs) integrate multiple neuronal events like synaptic inputs and intracellular potentials. LFP spatiotemporal features are particularly relevant in view of their applications both in research (e.g. for understanding brain rhythms, inter-areal neural communication and neuronal coding) and in the clinics (e.g. for improving invasive Brain-Machine Interface devices). However the relation between LFPs and spikes is complex and not fully understood. As spikes represent the fundamental currency of neuronal communication this gap in knowledge strongly limits our comprehension of neuronal phenomena underlying LFPs. We investigated the LFP-spike relation during tactile stimulation in primary somatosensory (S-I) cortex in the rat. First we quantified how reliably LFPs and spikes code for a stimulus occurrence. Then we used the information obtained from our analyses to design a predictive model for spike occurrence based on LFP inputs. The model was endowed with a flexible meta-structure whose exact form, both in parameters and structure, was estimated by using a multi-objective optimization strategy. Our method provided a set of nonlinear simple equations that maximized the match between models and true neurons in terms of spike timings and Peri Stimulus Time Histograms. We found that both LFPs and spikes can code for stimulus occurrence with millisecond precision, showing, however, high variability. Spike patterns were predicted significantly above chance for 75% of the neurons analysed. Crucially, the level of prediction accuracy depended on the reliability in coding for the stimulus occurrence. The best predictions were obtained when both spikes and LFPs were highly responsive to the stimuli. Spike reliability is known to depend on neuron intrinsic properties (i.e. on channel noise) and on spontaneous local network fluctuations. Our results suggest that the latter, measured through the LFP response variability, play a dominant role.

Voltage dependence of the rat chorda tympani response to Na+ salts: implications for the functional organization of taste receptor cells.

PubMed

Ye, Q; Heck, G L; DeSimone, J A

1993-07-01

1. Voltage-clamp and current-clamp data were obtained from a circumscribed region of the anterior rat lingual epithelium while simultaneously monitoring the afferent, stimulus-evoked, neural response from the same receptive field. 2. Chorda tympani (CT) responses at constant Na(+)-salt concentration were enhanced by submucosa negative voltage clamp and suppressed by positive voltage clamp. The complete CT response profile, including the time course of adaptation, was not uniquely determined by NaCl concentration alone. The response could be reproduced at different NaCl concentrations by applying a compensating voltage. 3. The form of the concentration and voltage dependence of the CT response indicates that the complete stimulus energy is the Na+ electrochemical potential difference across receptor cell apical membranes, and not Na+ concentration alone. This is the underlying principal behind the equivalence of chemical and electric taste for Na+ salts. 4. CT responses to sodium gluconate (25 and 200 mM) and 25 mM NaCl produced amiloride-insensitive components (AIC) of low magnitude. NaCl at 200 mM produced a significantly larger AIC. The AIC was voltage-clamp independent. The relative magnitude of the AIC was positively correlated with the transepithelial conductance of each salt. This suggests that the large AIC for 200 mM NaCl results from its relatively high permeability through the paracellular pathway. 5. Analysis of the CT response under voltage clamp revealed two anion effects on Na(+)-salt taste, both of which act through the paracellular shunt. 1) Anions modify the transepithelial potential (TP) across tight junctions and thereby modulate the cell receptor potential. This anion effect can be eliminated by voltage clamping the TP. 2) Sufficiently mobile anions facilitate electroneutral diffusion of Na+ salts through tight junctions. This effect is observed especially when Cl- is the anion and when the stimulus concentration favors NaCl influx, allowing Na+ to stimulate receptor cells from the submucosal side. Because the submucosal intercellular spaces are nearly isopotential regions, this effect is insensitive to voltage clamp of the TP. The large AIC associated with this anion effect is due to the low permeability of amiloride.

Assessment of anoxia tolerance and photoperiod dependence of GABAergic polarity in the pond snail Lymnaea stagnalis.

PubMed

Buck, Leslie T; Bond, Hilary C; Malik, Aqsa

2017-01-01

The pond snail Lymnaea stagnalis is reported to be anoxia-tolerant and if the tolerance mechanism is similar to that of the anoxia-tolerant painted turtle, GABA should play an important role. A potentially confounding factor investigating the role of GABA in anoxia tolerance are reports that GABA has both inhibitory and excitatory effects within L. stagnalis central ganglion. We therefore set out to determine if seasonality or photoperiod has an impact on: 1) the anoxia-tolerance of the intact pond snail, and 2) the response of isolated neuroganglia cluster F neurons to exogenous GABA application. L. stagnalis maintained on a natural summer light cycle were unable to survive any period of anoxic exposure, while those maintained on a natural winter light cycle survived a maximum of 4h. Using intracellular sharp electrode recordings from pedal ganglia cluster F neurons we show that there is a photoperiod dependent shift in the response to GABA. Snails exposed to a 16h:8h light:dark cycle in an environmental chamber (induced summer phenotype) exhibited hyperpolarizing inhibitory responses and those exposed to a 8h:16h light:dark cycle (induced winter phenotype) exhibited depolarizing excitatory responses to GABA application. Using gramicidin-perforated patch recordings we also found a photoperiod dependent shift in the reversal potential for GABA. We conclude that the opposing responses of L. stagnalis central neurons to GABA results from a shift in intracellular chloride concentration that is photoperiod dependent and is likely mediated through the relative efficacy of cation chloride co-transporters. Although the physiological ramifications of the photoperiod dependent shift are unknown this work potentially has important implications for the impact of artificial light pollution on animal health. Copyright © 2016 Elsevier Inc. All rights reserved.

Reticular influences on primary and augmenting responses in the somatosensory cortex.

PubMed

Steriade, M; Morin, D

1981-01-26

The effects of brief, conditioning trains of high-frequency pulses to the midbrain reticular formation (RF) on primary and augmenting responses of somatosensory (SI) cortex were investigated. Testing stimulation was applied to the ventrobasal (VB) thalamus or to the white matter (WM) beneath SI in VB-lesioned animals. The RF-elicited EEG activation was associated with increased firing rates of SI neurons, enhanced probability of early synaptic discharges to VB or WM stimuli, and significantly reduced duration of the suppressed firing period following an afferent VB or WM volley. The diminished latency of the postinhibitory rebound under RF stimulation had the consequence that, within 10/sec shock-train, the second stimulus was delivered following completion of the rebound component and, instead of an augmented potential, generated a field response of primary-type. The dependence of the RF-induced change in augmenting potentials upon the sharpening effect exerted on the preceding inhibitory-rebound sequence was corroborated by analyzing the RF influence on neurons with different time-course of recovery from inhibition. The replacement of augmenting potentials by primary responses under RF stimulation is advanced as the mechanism behind the obliteration of spontaneously developing 'type I' spindle-waves during EEG arousal. The demonstration of RF influences on SI responses to WM stimulation in VB-lesioned animals points out the cortical level of the effects. The reticulo-thalamo-cortical pathways underlying these influences are discussed.

Endocannabinoid-Dependent Long-Term Potentiation of Synaptic Transmission at Rat Barrel Cortex.

PubMed

Maglio, Laura Eva; Noriega-Prieto, José Antonio; Maraver, Maria Jesús; Fernández de Sevilla, David

2018-05-01

Brain-derived neurotrophic factor (BDNF) plays a critical role in modulating plasticity in sensory cortices. Indeed, a BDNF-dependent long-term potentiation (LTP) at distal basal excitatory synapses of Layer 5 pyramidal neurons (L5PNs) has been demonstrated in disinhibited rat barrel cortex slices. Although it is well established that this LTP requires the pairing of excitatory postsynaptic potentials (PSPs) with Ca2+ spikes, its induction when synaptic inhibition is working remains unexplored. Here we show that low-frequency stimulation at basal dendrites of L5PNs is able to trigger a PSP followed by an action potential (AP) and a slow depolarization (termed PSP-Ca2+ response) in thalamocortical slices without blocking synaptic inhibition. We demonstrate that AP barrage-mediated release of endocannabinoids (eCBs) from the recorded L5PNs induces PSP-Ca2+ response facilitation and BDNF-dependent LTP. Indeed, this LTP requires the type 1 cannabinoid receptors activation, is prevented by postsynaptic intracellular 1,2-bis(2-aminophenoxy) ethane-N,N,N,N'-tetraacetic acid (BAPTA) or the anandamide membrane transporter inhibitor AM404, and only occurs in L5PNs neurons showing depolarization-induced suppression of inhibition. Additionally, electrical stimulation at the posteromedial thalamic nucleus induced similar response and LTP. These results reveal a novel form of eCB-dependent LTP at L5PNs that could be relevant in the processing of sensory information in the barrel cortex.

Navy Operational Planner: Anti-Submarine Warfare with Time-Dependent Performance

DTIC Science & Technology

2017-09-01

PLANNER: ANTI-SUBMARINE WARFARE WITH TIME -DEPENDENT PERFORMANCE by Anthony M. Baldessari September 2017 Thesis Advisor: W. Matthew...reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instruction, searching...REPORT TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE NAVY OPERATIONAL PLANNER: ANTI-SUBMARINE WARFARE WITH TIME -DEPENDENT

Linearized blade row compression component model. Stability and frequency response analysis of a J85-3 compressor

NASA Technical Reports Server (NTRS)

Tesch, W. A.; Moszee, R. H.; Steenken, W. G.

1976-01-01

NASA developed stability and frequency response analysis techniques were applied to a dynamic blade row compression component stability model to provide a more economic approach to surge line and frequency response determination than that provided by time-dependent methods. This blade row model was linearized and the Jacobian matrix was formed. The clean-inlet-flow stability characteristics of the compressors of two J85-13 engines were predicted by applying the alternate Routh-Hurwitz stability criterion to the Jacobian matrix. The predicted surge line agreed with the clean-inlet-flow surge line predicted by the time-dependent method to a high degree except for one engine at 94% corrected speed. No satisfactory explanation of this discrepancy was found. The frequency response of the linearized system was determined by evaluating its Laplace transfer function. The results of the linearized-frequency-response analysis agree with the time-dependent results when the time-dependent inlet total-pressure and exit-flow function amplitude boundary conditions are less than 1 percent and 3 percent, respectively. The stability analysis technique was extended to a two-sector parallel compressor model with and without interstage crossflow and predictions were carried out for total-pressure distortion extents of 180 deg, 90 deg, 60 deg, and 30 deg.

Time-dependent nonequilibrium soft x-ray response during a spin crossover

DOE Office of Scientific and Technical Information (OSTI.GOV)

van Veenendaal, Michel

The rapid development of high-brilliance pulsed X-ray sources with femtosecond time resolution has created a need for a better theoretical understanding of the time-dependent soft-X-ray response of dissipative many-body quantum systems. It is demonstrated how soft-X-ray spectroscopies, such as X-ray absorption and resonant inelastic X-ray scattering at transition-metal L-edges, can provide insight into intersystem crossings, such as a spin crossover. The photoinduced doublet-to-quartet spin crossover on cobalt in Fe-Co Prussian blue analogues is used as an example to demonstrate how the X-ray response is affected by the dissipative nonequilibrium dynamics. The time-dependent soft-X-ray spectra provide a wealth of information thatmore » reflect the changes in the nonequilibrium initial state via continuously changing spectral lineshapes that cannot be decomposed into initial photoexcited and final metastable spectra, strong broadenings, a collapse of clear selection rules during the intersystem crossing, strong fluctuations in the isotropic branching ratio in X-ray absorption, and crystal-field collapse/oscillations and strongly time-dependent anti-Stokes processes in RIXS.« less

Exponential integrators in time-dependent density-functional calculations

NASA Astrophysics Data System (ADS)

Kidd, Daniel; Covington, Cody; Varga, Kálmán

2017-12-01

The integrating factor and exponential time differencing methods are implemented and tested for solving the time-dependent Kohn-Sham equations. Popular time propagation methods used in physics, as well as other robust numerical approaches, are compared to these exponential integrator methods in order to judge the relative merit of the computational schemes. We determine an improvement in accuracy of multiple orders of magnitude when describing dynamics driven primarily by a nonlinear potential. For cases of dynamics driven by a time-dependent external potential, the accuracy of the exponential integrator methods are less enhanced but still match or outperform the best of the conventional methods tested.

Pretreatment Differences in BOLD Response to Emotional Faces Correlate with Antidepressant Response to Scopolamine.

PubMed

Furey, Maura L; Drevets, Wayne C; Szczepanik, Joanna; Khanna, Ashish; Nugent, Allison; Zarate, Carlos A

2015-03-28

Faster acting antidepressants and biomarkers that predict treatment response are needed to facilitate the development of more effective treatments for patients with major depressive disorders. Here, we evaluate implicitly and explicitly processed emotional faces using neuroimaging to identify potential biomarkers of treatment response to the antimuscarinic, scopolamine. Healthy participants (n=15) and unmedicated-depressed major depressive disorder patients (n=16) participated in a double-blind, placebo-controlled crossover infusion study using scopolamine (4 μg/kg). Before and following scopolamine, blood oxygen-level dependent signal was measured using functional MRI during a selective attention task. Two stimuli comprised of superimposed pictures of faces and houses were presented. Participants attended to one stimulus component and performed a matching task. Face emotion was modulated (happy/sad) creating implicit (attend-houses) and explicit (attend-faces) emotion processing conditions. The pretreatment difference in blood oxygen-level dependent response to happy and sad faces under implicit and explicit conditions (emotion processing biases) within a-priori regions of interest was correlated with subsequent treatment response in major depressive disorder. Correlations were observed exclusively during implicit emotion processing in the regions of interest, which included the subgenual anterior cingulate (P<.02) and middle occipital cortices (P<.02). The magnitude and direction of differential blood oxygen-level- dependent response to implicitly processed emotional faces prior to treatment reflect the potential to respond to scopolamine. These findings replicate earlier results, highlighting the potential for pretreatment neural activity in the middle occipital cortices and subgenual anterior cingulate to inform us about the potential to respond clinically to scopolamine. Published by Oxford University Press on behalf of CINP 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Laser-excited optical emission response of CdTe quantum dot/polymer nanocomposite under shock compression

NASA Astrophysics Data System (ADS)

Xiao, Pan; Kang, Zhitao; Bansihev, Alexandr A.; Breidenich, Jennifer; Scripka, David A.; Christensen, James M.; Summers, Christopher J.; Dlott, Dana D.; Thadhani, Naresh N.; Zhou, Min

2016-01-01

Laser-driven shock compression experiments and corresponding finite element method simulations are carried out to investigate the blueshift in the optical emission spectra under continuous laser excitation of a dilute composite consisting of 0.15% CdTe quantum dots by weight embedded in polyvinyl alcohol polymer. This material is a potential candidate for use as internal stress sensors. The analyses focus on the time histories of the wavelength blue-shift for shock loading with pressures up to 7.3 GPa. The combined measurements and calculations allow a relation between the wavelength blueshift and pressure for the loading conditions to be extracted. It is found that the blueshift first increases with pressure to a maximum and subsequently decreases with pressure. This trend is different from the monotonic increase of blueshift with pressure observed under conditions of quasistatic hydrostatic compression. Additionally, the blueshift in the shock experiments is much smaller than that in hydrostatic experiments at the same pressure levels. The differences in responses are attributed to the different stress states achieved in the shock and hydrostatic experiments and the time dependence of the mechanical response of the polymer in the composite. The findings offer a potential guide for the design and development of materials for internal stress sensors for shock conditions.

The Department of Defense energy vulnerabilities: Potential problems and observations

NASA Astrophysics Data System (ADS)

Freiwald, D. A.; Berger, M. E.; Roach, J. F.

1982-08-01

The Department of Defense is almost entirely dependent on civilian energy supplies to meet its needs in both peacetime and periods of heightened conflict. There are a number of potential vulnerabilities to the continual and timely supply of energy to both the civilian and military sectors. These include denial of the energy resources themselves, disruption of critical transportation networks, destruction of storage facilities, and interruption of electrical power. This report briefly reviews the present situation for provision of energy from the civilian sector to the military. General vulnerabilities of the existing energy supply system are identified, along with the potential for armed aggression (including terrorist and sabotage activities) against the energy network. Conclusions and some tentative observations are made as to a proper response to the existing vulnerabilities.

Light-induced modification of plant plasma membrane ion transport.

PubMed

Marten, I; Deeken, R; Hedrich, R; Roelfsema, M R G

2010-09-01

Light is not only the driving force for electron and ion transport in the thylakoid membrane, but also regulates ion transport in various other membranes of plant cells. Light-dependent changes in ion transport at the plasma membrane and associated membrane potential changes have been studied intensively over the last century. These studies, with various species and cell types, revealed that apart from regulation by chloroplasts, plasma membrane transport can be controlled by phytochromes, phototropins or channel rhodopsins. In this review, we compare light-dependent plasma membrane responses of unicellular algae (Eremosphaera and Chlamydomonas), with those of a multicellular alga (Chara), liverworts (Conocephalum), mosses (Physcomitrella) and several angiosperm cell types. Light-dependent plasma membrane responses of Eremosphaera and Chara are characterised by the dominant role of K(+) channels during membrane potential changes. In most other species, the Ca(2+)-dependent activation of plasma membrane anion channels represents a general light-triggered event. Cell type-specific responses are likely to have evolved by modification of this general response or through the development of additional light-dependent signalling pathways. Future research to elucidate these light-activated signalling chains is likely to benefit from the recent identification of S-type anion channel genes and proteins capable of regulating these channels.

Kinetics of ROS generation induced by polycyclic aromatic hydrocarbons and organic extracts from ambient air particulate matter in model human lung cell lines.

PubMed

Libalova, Helena; Milcova, Alena; Cervena, Tereza; Vrbova, Kristyna; Rossnerova, Andrea; Novakova, Zuzana; Topinka, Jan; Rossner, Pavel

2018-03-01

Polycyclic aromatic hydrocarbons (PAHs) associated with particulate matter (PM) may induce oxidative damage via reactive oxygen species (ROS) generation. However, the kinetics of ROS production and the link with antioxidant response induction has not been well studied. To elucidate the differences in oxidative potential of individual PAH compounds and extractable organic matter (EOM) from PM containing various PAH mixtures, we studied ROS formation and antioxidant response [total antioxidant capacity (TAC) and expression of HMOX1 and TXNRD1] in human alveolar basal epithelial cells (A549 cells) and human embryonic lung fibroblasts (HEL12469 cells). We treated the cells with three concentrations of model PAHs (benzo[a]pyrene, B[a]P; 3-nitrobenzanthrone, 3-NBA) and EOM from PM <2.5 μm (PM2.5). ROS levels were evaluated at 8 time intervals (30 min-24 h). In both cell lines, B[a]P treatment was associated with a time-dependent decrease of ROS levels. This trend was more pronounced in HEL12469 cells and was accompanied by increased TAC. A similar response was observed upon 3-NBA treatment in HEL12469 cells. In A549 cells, however, this compound significantly increased superoxide levels. This response was accompanied by the decrease of TAC as well as HMOX1 and TXNRD1 expression. In both cell lines, a short-time exposure to EOMs tended to increase ROS levels, while a marked decrease was observed after longer treatment periods. This was accompanied by the induction of HMOX1 and TXNRD1 expression in HEL12469 cells and increased TAC in A549 cells. In summary, our data indicate that in the studied cell lines B[a]P and EOMs caused a time-dependent decrease of intracellular ROS levels, probably due to the activation of the antioxidant response. This response was not detected in A549 cells following 3-NBA treatment, which acted as a strong superoxide inducer. Pro-oxidant properties of EOMs are limited to short-time exposure periods. Copyright © 2018 Elsevier B.V. All rights reserved.

Density-mediated, context-dependent consumer-resource interactions between ants and extrafloral nectar plants.

PubMed

Chamberlain, Scott A; Holland, J Nathaniel

2008-05-01

Interspecific interactions are often mediated by the interplay between resource supply and consumer density. The supply of a resource and a consumer's density response to it may in turn yield context-dependent use of other resources. Such consumer-resource interactions occur not only for predator-prey and competitive interactions, but for mutualistic ones as well. For example, consumer-resource interactions between ants and extrafloral nectar (EFN) plants are often mutualistic, as EFN resources attract and reward ants which protect plants from herbivory. Yet, ants also commonly exploit floral resources, leading to antagonistic consumer-resource interactions by disrupting pollination and plant reproduction. EFN resources associated with mutualistic ant-plant interactions may also mediate antagonistic ant-flower interactions through the aggregative density response of ants on plants, which could either exacerbate ant-flower interactions or alternatively satiate and distract ants from floral resources. In this study, we examined how EFN resources mediate the density response of ants on senita cacti in the Sonoran Desert and their context-dependent use of floral resources. Removal of EFN resources reduced the aggregative density of ants on plants, both on hourly and daily time scales. Yet, the increased aggregative ant density on plants with EFN resources decreased rather than increased ant use of floral resources, including contacts with and time spent in flowers. Behavioral assays showed no confounding effect of floral deterrents on ant-flower interactions. Thus, ant use of floral resources depends on the supply of EFN resources, which mediates the potential for both mutualistic and antagonistic interactions by increasing the aggregative density of ants protecting plants, while concurrently distracting ants from floral resources. Nevertheless, only certain years and populations of study showed an increase in plant reproduction through herbivore protection or ant distraction from floral resources. Despite pronounced effects of EFN resources mediating the aggregative density of ants on plants and their context-dependent use of floral resources, consumer-resource interactions remained largely commensalistic.

The Speed of Visual Attention and Motor-Response Decisions in Adult Attention-Deficit/Hyperactivity Disorder.

PubMed

Cross-Villasana, Fernando; Finke, Kathrin; Hennig-Fast, Kristina; Kilian, Beate; Wiegand, Iris; Müller, Hermann Joseph; Möller, Hans-Jürgen; Töllner, Thomas

2015-07-15

Adults with attention-deficit/hyperactivity disorder (ADHD) exhibit slowed reaction times (RTs) in various attention tasks. The exact origins of this slowing, however, have not been established. Potential candidates are early sensory processes mediating the deployment of focal attention, stimulus response translation processes deciding upon the appropriate motor response, and motor processes generating the response. We combined mental chronometry (RT) measures of adult ADHD (n = 15) and healthy control (n = 15) participants with their lateralized event-related potentials during the performance of a visual search task to differentiate potential sources of slowing at separable levels of processing: the posterior contralateral negativity (PCN) was used to index focal-attentional selection times, while the lateralized readiness potentials synchronized to stimulus and response events were used to index the times taken for response selection and production, respectively. To assess the clinical relevance of event-related potentials, a correlation analysis between neural measures and subjective current and retrospective ADHD symptom ratings was performed. ADHD patients exhibited slower RTs than control participants, which were accompanied by prolonged PCN and lateralized readiness potentials synchronized to stimulus, but not lateralized readiness potentials synchronized to response events, latencies. Moreover, the PCN timing was positively correlated with ADHD symptom ratings. The behavioral RT slowing of adult ADHD patients was based on a summation of internal processing delays arising at perceptual and response selection stages; motor response production, by contrast, was not impaired. The correlation between PCN times and ADHD symptom ratings suggests that this brain signal may serve as a potential candidate for a neurocognitive endophenotype of ADHD. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

TimeXNet Web: Identifying cellular response networks from diverse omics time-course data.

PubMed

Tan, Phit Ling; López, Yosvany; Nakai, Kenta; Patil, Ashwini

2018-05-14

Condition-specific time-course omics profiles are frequently used to study cellular response to stimuli and identify associated signaling pathways. However, few online tools allow users to analyze multiple types of high-throughput time-course data. TimeXNet Web is a web server that extracts a time-dependent gene/protein response network from time-course transcriptomic, proteomic or phospho-proteomic data, and an input interaction network. It classifies the given genes/proteins into time-dependent groups based on the time of their highest activity and identifies the most probable paths connecting genes/proteins in consecutive groups. The response sub-network is enriched in activated genes/proteins and contains novel regulators that do not show any observable change in the input data. Users can view the resultant response network and analyze it for functional enrichment. TimeXNet Web supports the analysis of high-throughput data from multiple species by providing high quality, weighted protein-protein interaction networks for 12 model organisms. http://txnet.hgc.jp/. ashwini@hgc.jp. Supplementary data are available at Bioinformatics online.

A combined experimental atomic force microscopy-based nanoindentation and computational modeling approach to unravel the key contributors to the time-dependent mechanical behavior of single cells.

PubMed

Florea, Cristina; Tanska, Petri; Mononen, Mika E; Qu, Chengjuan; Lammi, Mikko J; Laasanen, Mikko S; Korhonen, Rami K

2017-02-01

Cellular responses to mechanical stimuli are influenced by the mechanical properties of cells and the surrounding tissue matrix. Cells exhibit viscoelastic behavior in response to an applied stress. This has been attributed to fluid flow-dependent and flow-independent mechanisms. However, the particular mechanism that controls the local time-dependent behavior of cells is unknown. Here, a combined approach of experimental AFM nanoindentation with computational modeling is proposed, taking into account complex material behavior. Three constitutive models (porohyperelastic, viscohyperelastic, poroviscohyperelastic) in tandem with optimization algorithms were employed to capture the experimental stress relaxation data of chondrocytes at 5 % strain. The poroviscohyperelastic models with and without fluid flow allowed through the cell membrane provided excellent description of the experimental time-dependent cell responses (normalized mean squared error (NMSE) of 0.003 between the model and experiments). The viscohyperelastic model without fluid could not follow the entire experimental data that well (NMSE = 0.005), while the porohyperelastic model could not capture it at all (NMSE = 0.383). We also show by parametric analysis that the fluid flow has a small, but essential effect on the loading phase and short-term cell relaxation response, while the solid viscoelasticity controls the longer-term responses. We suggest that the local time-dependent cell mechanical response is determined by the combined effects of intrinsic viscoelasticity of the cytoskeleton and fluid flow redistribution in the cells, although the contribution of fluid flow is smaller when using a nanosized probe and moderate indentation rate. The present approach provides new insights into viscoelastic responses of chondrocytes, important for further understanding cell mechanobiological mechanisms in health and disease.

Time-dependent micromechanical responses of breast cancer cells and adjacent fibroblasts to electric treatment.

PubMed

Yizraeli, Maayan Lia; Weihs, Daphne

2011-12-01

Direct-current, low-intensity, electric fields were suggested as a minimally invasive treatment for various cancers. The tumor microenvironment may affect treatment efficacy, albeit it has not generally been considered when evaluating novel anti-cancer treatments. We evaluate the effects of electric treatment on epithelial, breast-cancer cells, co-cultured with non-cancerous fibroblasts, a simplified model for the tumor-microenvironment. We evaluate changes in morphology, cytoskeleton, and focus on dynamic intracellular structure and mechanics. Multiple-particle tracking was used within living cells to quantify time-dependent structural and mechanical changes. Cancer cells suffer severe cell death and exhibit transient rounding and changes in internal structural and mechanics. Interestingly, treating cancer cells in co-culture with fibroblasts delays and reduces their responses to treatment. Our particle-tracking data indicates a mechanism relating the observed changes in intracellular transport to transient changes in the microtubule network and its motors. In contrast, fibroblasts are only minimally affected by treatment, separately or in co-culture. To conclude, intracellular mechanics reveal time-dependent responses after treatment, unavailable by bulk measurements. This time-dependence could provide a window of opportunity for continued treatment. We demonstrate the importance of evaluating anti-cancer treatments within their microenvironment, which can affect response magnitude and time-course.

Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity.

PubMed

Albers, Christian; Westkott, Maren; Pawelzik, Klaus

2016-01-01

Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP). Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious) and strong (teacher) spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns.

Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity

PubMed Central

Albers, Christian; Westkott, Maren; Pawelzik, Klaus

2016-01-01

Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP). Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious) and strong (teacher) spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns. PMID:26900845

Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder.

PubMed

Szczepanik, Joanna; Nugent, Allison C; Drevets, Wayne C; Khanna, Ashish; Zarate, Carlos A; Furey, Maura L

2016-08-30

The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus-dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy controls performed an attention shifting task involving emotional faces while undergoing functional magnetic resonance imaging (fMRI). We found that blood oxygenation level dependent (BOLD) signal in the amygdala acquired while MDD patients processed sad face stimuli correlated positively with antidepressant response to scopolamine. Amygdalar response to sad faces in MDD patients who did not respond to scopolamine did not differ from that of healthy controls. This suggests that the pre-treatment task elicited amygdalar activity that may constitute a biomarker of antidepressant treatment response to scopolamine. Furthermore, in MDD patients who responded to scopolamine, we observed a post-scopolamine stimulus processing shift towards a pattern demonstrated by healthy controls, indicating a change in stimulus-dependent neural response potentially driven by attenuated cholinergic activity in the amygdala. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Inhalation Frequency Controls Reformatting of Mitral/Tufted Cell Odor Representations in the Olfactory Bulb.

PubMed

Díaz-Quesada, Marta; Youngstrom, Isaac A; Tsuno, Yusuke; Hansen, Kyle R; Economo, Michael N; Wachowiak, Matt

2018-02-28

In mammals, olfactory sensation depends on inhalation, which controls activation of sensory neurons and temporal patterning of central activity. Odor representations by mitral and tufted (MT) cells, the main output from the olfactory bulb (OB), reflect sensory input as well as excitation and inhibition from OB circuits, which may change as sniff frequency increases. To test the impact of sampling frequency on MT cell odor responses, we obtained whole-cell recordings from MT cells in anesthetized male and female mice while varying inhalation frequency via tracheotomy, allowing comparison of inhalation-linked responses across cells. We characterized frequency effects on MT cell responses during inhalation of air and odorants using inhalation pulses and also "playback" of sniffing recorded from awake mice. Inhalation-linked changes in membrane potential were well predicted across frequency from linear convolution of 1 Hz responses; and, as frequency increased, near-identical temporal responses could emerge from depolarizing, hyperpolarizing, or multiphasic MT responses. However, net excitation was not well predicted from 1 Hz responses and varied substantially across MT cells, with some cells increasing and others decreasing in spike rate. As a result, sustained odorant sampling at higher frequencies led to increasing decorrelation of the MT cell population response pattern over time. Bulk activation of sensory inputs by optogenetic stimulation affected MT cells more uniformly across frequency, suggesting that frequency-dependent decorrelation emerges from odor-specific patterns of activity in the OB network. These results suggest that sampling behavior alone can reformat early sensory representations, possibly to optimize sensory perception during repeated sampling. SIGNIFICANCE STATEMENT Olfactory sensation in mammals depends on inhalation, which increases in frequency during active sampling of olfactory stimuli. We asked how inhalation frequency can shape the neural coding of odor information by recording from projection neurons of the olfactory bulb while artificially varying odor sampling frequency in the anesthetized mouse. We found that sampling an odor at higher frequencies led to diverse changes in net responsiveness, as measured by action potential output, that were not predicted from low-frequency responses. These changes led to a reorganization of the pattern of neural activity evoked by a given odorant that occurred preferentially during sustained, high-frequency inhalation. These results point to a novel mechanism for modulating early sensory representations solely as a function of sampling behavior. Copyright © 2018 the authors 0270-6474/18/382189-18$15.00/0.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Black, Adrienne T.; Hayden, Patrick J.; Casillas, Robert P.

Sulfur mustard is a potent vesicant that induces inflammation, edema and blistering following dermal exposure. To assess molecular mechanisms mediating these responses, we analyzed the effects of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide, on EpiDerm-FT{sup TM}, a commercially available full-thickness human skin equivalent. CEES (100-1000 {mu}M) caused a concentration-dependent increase in pyknotic nuclei and vacuolization in basal keratinocytes; at high concentrations (300-1000 {mu}M), CEES also disrupted keratin filament architecture in the stratum corneum. This was associated with time-dependent increases in expression of proliferating cell nuclear antigen, a marker of cell proliferation, and poly(ADP-ribose) polymerase (PARP) and phosphorylated histonemore » H2AX, markers of DNA damage. Concentration- and time-dependent increases in mRNA and protein expression of eicosanoid biosynthetic enzymes including COX-2, 5-lipoxygenase, microsomal PGE{sub 2} synthases, leukotriene (LT) A{sub 4} hydrolase and LTC{sub 4} synthase were observed in CEES-treated skin equivalents, as well as in antioxidant enzymes, glutathione S-transferases A1-2 (GSTA1-2), GSTA3 and GSTA4. These data demonstrate that CEES induces rapid cellular damage, cytotoxicity and inflammation in full-thickness skin equivalents. These effects are similar to human responses to vesicants in vivo and suggest that the full thickness skin equivalent is a useful in vitro model to characterize the biological effects of mustards and to develop potential therapeutics.« less

Kinetic operational models of agonism for G-protein-coupled receptors.

PubMed

Hoare, Samuel R J; Pierre, Nicolas; Moya, Arturo Gonzalez; Larson, Brad

2018-06-07

The application of kinetics to research and therapeutic development of G-protein-coupled receptors has become increasingly valuable. Pharmacological models provide the foundation of pharmacology, providing concepts and measurable parameters such as efficacy and potency that have underlain decades of successful drug discovery. Currently there are few pharmacological models that incorporate kinetic activity in such a way as to yield experimentally-accessible drug parameters. In this study, a kinetic model of pharmacological response was developed that provides a kinetic descriptor of efficacy (the transduction rate constant, k τ ) and allows measurement of receptor-ligand binding kinetics from functional data. The model assumes: (1) receptor interacts with a precursor of the response ("Transduction potential") and converts it to the response. (2) The response can decay. Familiar response vs time plots emerge, depending on whether transduction potential is depleted and/or response decays. These are the straight line, the "association" exponential curve, and the rise-and-fall curve. Convenient, familiar methods are described for measuring the model parameters and files are provided for the curve-fitting program Prism (GraphPad Software) that can be used as a guide. The efficacy parameter k τ is straightforward to measure and accounts for receptor reserve; all that is required is measurement of response over time at a maximally-stimulating concentration of agonist. The modular nature of the model framework allows it to be extended. Here this is done to incorporate antagonist-receptor binding kinetics and slow agonist-receptor equilibration. In principle, the modular framework can incorporate other cellular processes, such as receptor desensitization. The kinetic response model described here can be applied to measure kinetic pharmacological parameters than can be used to advance the understanding of GPCR pharmacology and optimize new and improved therapeutics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Collaboration in natural resource governance: reconciling stakeholder expectations in deer management in Scotland.

PubMed

Davies, Althea L; White, Rehema M

2012-12-15

The challenges of integrated, adaptive and ecosystem management are leading government agencies to adopt participatory modes of engagement. Collaborative governance is a form of participation in which stakeholders co-produce goals and strategies and share responsibilities and resources. We assess the potential and challenges of collaborative governance as a mechanism to provide an integrated, ecosystem approach to natural resource management, using red deer in Scotland as a case study. Collaborative Deer Management Groups offer a well-established example of a 'bridging organisation', intended to reduce costs and facilitate decision making and learning across institutions and scales. We examine who initiates collaborative processes and why, what roles different actors adopt and how these factors influence the outcomes, particularly at a time of changing values, management and legislative priorities. Our findings demonstrate the need for careful consideration of where and how shared responsibility might be best implemented and sustained as state agencies often remain key to the process, despite the partnership intention. Differing interpretations between agencies and landowners of the degree of autonomy and division of responsibilities involved in 'collaboration' can create tension, while the diversity of landowner priorities brings additional challenges for defining shared goals in red deer management and in other cases. Effective maintenance depends on appropriate role allocation and adoption of responsibilities, definition of convergent values and goals, and establishing communication and trust in institutional networks. Options that may help private stakeholders offset the costs of accepting responsibility for delivering public benefits need to be explicitly addressed to build capacity and support adaptation. This study indicates that collaborative governance has the potential to help reconcile statutory obligations with stakeholder empowerment. The potential of collaboration to reduce the costs of sustainable management remains contentious and, in times of increasing resource constraints, the potential mismatch between resource investment and anticipated goals is likely to become a critical issue, which may challenge the goals and capacity of the state and existing managers. Copyright © 2012 Elsevier Ltd. All rights reserved.

Optical stimulation of the hearing and deaf cochlea under thermal and stress confinement condition

NASA Astrophysics Data System (ADS)

Schultz, M.; Baumhoff, P.; Kallweit, N.; Sato, M.; Krüger, A.; Ripken, T.; Lenarz, T.; Kral, A.

2014-03-01

There is a controversy, to which extend cochlear stimulation with near infrared laser pulses at a wavelength of 1860 nm is based on optoacoustic stimulation of intact hair cells or -in contrast- is based on direct stimulation of the nerve cells in absence of functional hair cells. Thermal and stress confinement conditions apply, because of the pulse duration range (5 ns, 10 μs-20 ms) of the two lasers used. The dependency of the signal characteristics on pulse peak power and pulse duration was investigated in this study. The compound action potential (CAP) was measured during stimulation of the cochlea of four anaesthetized guinea pigs, which were hearing at first and afterwards acutely deafened using intracochlear neomycin-rinsing. For comparison hydrophone measurements in a water tank were performed to investigate the optoacoustic signals at different laser interaction regimes. With rising pulse peak power CAPs of the hearing animals showed first a threshold, then a positively correlated and finally a saturating dependency. CAPs also showed distinct responses at laser onset and offset separated with the pulse duration. At pulse durations shorter than physiological response times the signals merged. Basically the same signal characteristics were observed in the optoacoustic hydrophone measurements, scaled with the sensitivity and response time of the hydrophone. Taking together the qualitative correspondence in the signal response and the absence of any CAPs in deafened animals our results speak in favor of an optoacoustic stimulation of intact hair cells rather than a direct stimulation of nerve cells.

Voltage-dependent dynamic FRET signals from the transverse tubules in mammalian skeletal muscle fibers.

PubMed

DiFranco, Marino; Capote, Joana; Quiñonez, Marbella; Vergara, Julio L

2007-12-01

Two hybrid voltage-sensing systems based on fluorescence resonance energy transfer (FRET) were used to record membrane potential changes in the transverse tubular system (TTS) and surface membranes of adult mice skeletal muscle fibers. Farnesylated EGFP or ECFP (EGFP-F and ECFP-F) were used as immobile FRET donors, and either non-fluorescent (dipicrylamine [DPA]) or fluorescent (oxonol dye DiBAC(4)(5)) lipophilic anions were used as mobile energy acceptors. Flexor digitorum brevis (FDB) muscles were transfected by in vivo electroporation with pEGFP-F and pECFP-F. Farnesylated fluorescent proteins were efficiently expressed in the TTS and surface membranes. Voltage-dependent optical signals resulting from resonance energy transfer from fluorescent proteins to DPA were named QRET transients, to distinguish them from FRET transients recorded using DiBAC(4)(5). The peak DeltaF/F of QRET transients elicited by action potential stimulation is twice larger in fibers expressing ECFP-F as those with EGFP-F (7.1% vs. 3.6%). These data provide a unique experimental demonstration of the importance of the spectral overlap in FRET. The voltage sensitivity of QRET and FRET signals was demonstrated to correspond to the voltage-dependent translocation of the charged acceptors, which manifest as nonlinear components in current records. For DPA, both electrical and QRET data were predicted by radial cable model simulations in which the maximal time constant of charge translocation was 0.6 ms. FRET signals recorded in response to action potentials in fibers stained with DiBAC(4)(5) exhibit DeltaF/F amplitudes as large as 28%, but their rising phase was slower than those of QRET signals. Model simulations require a time constant for charge translocation of 1.6 ms in order to predict current and FRET data. Our results provide the basis for the potential use of lipophilic ions as tools to test for fast voltage-dependent conformational changes of membrane proteins in the TTS.

Effect Anticipation Affects Perceptual, Cognitive, and Motor Phases of Response Preparation: Evidence from an Event-Related Potential (ERP) Study

PubMed Central

Harrison, Neil R.; Ziessler, Michael

2016-01-01

The anticipation of action effects is a basic process that can be observed even for key-pressing responses in a stimulus-response paradigm. In Ziessler et al.’s (2012) experiments participants first learned arbitrary effects of key-pressing responses. In the test phase an imperative stimulus determined the response, but participants withheld the response until a Go-stimulus appeared. Reaction times (RTs) were shorter if the Go-stimulus was compatible with the learned response effect. This is strong evidence that effect representations were activated during response planning. Here, we repeated the experiment using event-related potentials (ERPs), and we found that Go-stimulus locked ERPs depended on the compatibility relationship between the Go-stimulus and the response effect. In general, this supports the interpretation of the behavioral data. More specifically, differences in the ERPs between compatible and incompatible Go-stimuli were found for the early perceptual P1 component and the later frontal P2 component. P1 differences were found only in the second half of the experiment and for long stimulus onset asynchronies (SOAs) between imperative stimulus and Go-stimulus, i.e., when the effect was fully anticipated and the perceptual system was prepared for the effect-compatible Go-stimulus. P2 amplitudes, likely associated with evaluation and conflict detection, were larger when Go-stimulus and effect were incompatible; presumably, incompatibility increased the difficulty of effect anticipation. Onset of response-locked lateralized readiness potentials (R-LRPs) occurred earlier under incompatible conditions indicating extended motor processing. Together, these results strongly suggest that effect anticipation affects all (i.e., perceptual, cognitive, and motor) phases of response preparation. PMID:26858621

Effect Anticipation Affects Perceptual, Cognitive, and Motor Phases of Response Preparation: Evidence from an Event-Related Potential (ERP) Study.

PubMed

Harrison, Neil R; Ziessler, Michael

2016-01-01

The anticipation of action effects is a basic process that can be observed even for key-pressing responses in a stimulus-response paradigm. In Ziessler et al.'s (2012) experiments participants first learned arbitrary effects of key-pressing responses. In the test phase an imperative stimulus determined the response, but participants withheld the response until a Go-stimulus appeared. Reaction times (RTs) were shorter if the Go-stimulus was compatible with the learned response effect. This is strong evidence that effect representations were activated during response planning. Here, we repeated the experiment using event-related potentials (ERPs), and we found that Go-stimulus locked ERPs depended on the compatibility relationship between the Go-stimulus and the response effect. In general, this supports the interpretation of the behavioral data. More specifically, differences in the ERPs between compatible and incompatible Go-stimuli were found for the early perceptual P1 component and the later frontal P2 component. P1 differences were found only in the second half of the experiment and for long stimulus onset asynchronies (SOAs) between imperative stimulus and Go-stimulus, i.e., when the effect was fully anticipated and the perceptual system was prepared for the effect-compatible Go-stimulus. P2 amplitudes, likely associated with evaluation and conflict detection, were larger when Go-stimulus and effect were incompatible; presumably, incompatibility increased the difficulty of effect anticipation. Onset of response-locked lateralized readiness potentials (R-LRPs) occurred earlier under incompatible conditions indicating extended motor processing. Together, these results strongly suggest that effect anticipation affects all (i.e., perceptual, cognitive, and motor) phases of response preparation.

Enhancement of life cycle assessment (LCA) methodology to include the effect of surface albedo on climate change: Comparing black and white roofs.

PubMed

Susca, Tiziana

2012-04-01

Traditionally, life cycle assessment (LCA) does not estimate a key property: surface albedo. Here an enhancement of the LCA methodology has been proposed through the development and employment of a time-dependent climatological model for including the effect of surface albedo on climate. The theoretical findings derived by the time-dependent model have been applied to the case study of a black and a white roof evaluated in the time-frames of 50 and 100 years focusing on the impact on global warming potential. The comparative life cycle impact assessment of the two roofs shows that the high surface albedo plays a crucial role in offsetting radiative forcings. In the 50-year time horizon, surface albedo is responsible for a decrease in CO(2)eq of 110-184 kg and 131-217 kg in 100 years. Furthermore, the white roof compared to the black roof, due to the high albedo, decreases the annual energy use of about 3.6-4.5 kWh/m(2). Copyright © 2011 Elsevier Ltd. All rights reserved.

Simplification of the time-dependent generalized self-interaction correction method using two sets of orbitals: Application of the optimized effective potential formalism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Messud, J.; Dinh, P. M.; Suraud, Eric

2009-10-15

We propose a simplification of the time-dependent self-interaction correction (TD-SIC) method using two sets of orbitals, applying the optimized effective potential (OEP) method. The resulting scheme is called time-dependent 'generalized SIC-OEP'. A straightforward approximation, using the spatial localization of one set of orbitals, leads to the 'generalized SIC-Slater' formalism. We show that it represents a great improvement compared to the traditional SIC-Slater and Krieger-Li-Iafrate formalisms.

Simplification of the time-dependent generalized self-interaction correction method using two sets of orbitals: Application of the optimized effective potential formalism

NASA Astrophysics Data System (ADS)

Messud, J.; Dinh, P. M.; Reinhard, P.-G.; Suraud, Eric

2009-10-01

We propose a simplification of the time-dependent self-interaction correction (TD-SIC) method using two sets of orbitals, applying the optimized effective potential (OEP) method. The resulting scheme is called time-dependent “generalized SIC-OEP.” A straightforward approximation, using the spatial localization of one set of orbitals, leads to the “generalized SIC-Slater” formalism. We show that it represents a great improvement compared to the traditional SIC-Slater and Krieger-Li-Iafrate formalisms.

Energy shift and conduction-to-valence band transition mediated by a time-dependent potential barrier in graphene

NASA Astrophysics Data System (ADS)

Chaves, Andrey; da Costa, D. R.; de Sousa, G. O.; Pereira, J. M.; Farias, G. A.

2015-09-01

We investigate the scattering of a wave packet describing low-energy electrons in graphene by a time-dependent finite-step potential barrier. Our results demonstrate that, after Klein tunneling through the barrier, the electron acquires an extra energy which depends on the rate of change of the barrier height with time. If this rate is negative, the electron loses energy and ends up as a valence band state after leaving the barrier, which effectively behaves as a positively charged quasiparticle.

Ecosystem Processes at the Watershed Scale: Stability and Resilience of Catchment Spatial Structure and Function to Disturbance

NASA Astrophysics Data System (ADS)

Baron, J.; Mast, A.; Clow, D. W.; Wetherbee, G. A.

2014-12-01

Ecohydrological systems evolve spontaneously in response to geologic, hydroclimate and biodiversity drivers. The stability and resilience of these systems to multiple disturbances can be addressed over specific temporal extents, potentially embedded within long term transience in response to geologic or climate change. The limits of ecohydrological resilience of system state in terms of vegetation canopy and soil catenae and the space/time distribution of water, carbon and nutrient cycling is determined by a set of critical feedbacks and potential substitutions of plant functional forms in response to disturbance. The ability of forest systems to return to states functionally similar to states prior to major disturbance, or combinations of multiple disturbances, is a critical question given increasing hydroclimate extremes, biological invasions, and human disturbance. Over the past century, forest landscape ecological patterns appear to have the ability to recover from significant disturbance and re-establish similar hydrological and ecological function in humid, biodiverse regions such as the southern Appalachians, and potentially drier forest ecosystems. Understanding and prediction of past and future long term dynamics requires explicit representation of spatial and temporal feedbacks and dependencies between hydrological, ecosystem and geomorphic processes, and the spatial pattern of species or plant functional type (PFT). Comprehensive models of watershed ecohydrological resilience requires careful balance between the level of process and parameter detail between the interacting components, relative to the structure, organization, space and time scales of the landscape.

Synthesis and characterization of stimuli-responsive polypropylene containing N-vinylcaprolactam and N-vinylimidazole obtained by ionizing radiation.

PubMed

Zavala-Lagunes, Edgar; Ruiz, Juan-Carlos; Varca, Gustavo H C; Bucio, Emilio

2016-10-01

Polypropylene films were grafted with thermo-responsive N-vinylcaprolactam and pH-responsive N-vinylimidazole polymers by means of gamma radiation using pre-irradiation and direct methods, in order to functionalize the films with thermo- and/or pH-responsiveness. The dependence of grafting yield on parameters such as co-monomer concentration, pre-irradiation dose, temperature, and reaction time was evaluated. The samples were characterized by Fourier transform infrared and X-ray photoelectron spectroscopies, differential scanning calorimetry, thermogravimetric analysis, swelling studies in different solvents, and water contact angle. The grafted copolymers presented thermo- and pH-sensitiveness, highlighting their potential as advanced biomaterials, capable of providing adequate environment for hosting and sustained release of antimicrobial drugs bearing cationic moieties, such as groups of diclofenac, while still exhibiting good cytocompatibility. Copyright © 2016 Elsevier B.V. All rights reserved.

Gaps in knowledge and data driving uncertainty in models of photosynthesis.

PubMed

Dietze, Michael C

2014-02-01

Regional and global models of the terrestrial biosphere depend critically on models of photosynthesis when predicting impacts of global change. This paper focuses on identifying the primary data needs of these models, what scales drive uncertainty, and how to improve measurements. Overall, there is a need for an open, cross-discipline database on leaf-level photosynthesis in general, and response curves in particular. The parameters in photosynthetic models are not constant through time, space, or canopy position but there is a need for a better understanding of whether relationships with drivers, such as leaf nitrogen, are themselves scale dependent. Across time scales, as ecosystem models become more sophisticated in their representations of succession they needs to be able to approximate sunfleck responses to capture understory growth and survival. At both high and low latitudes, photosynthetic data are inadequate in general and there is a particular need to better understand thermal acclimation. Simple models of acclimation suggest that shifts in optimal temperature are important. However, there is little advantage to synoptic-scale responses and circadian rhythms may be more beneficial than acclimation over shorter timescales. At high latitudes, there is a need for a better understanding of low-temperature photosynthetic limits, while at low latitudes the need is for a better understanding of phosphorus limitations on photosynthesis. In terms of sampling, measuring multivariate photosynthetic response surfaces are potentially more efficient and more accurate than traditional univariate response curves. Finally, there is a need for greater community involvement in model validation and model-data synthesis.

Recent Advances in Drug Design and Drug Discovery for Androgen-Dependent Diseases

PubMed Central

Cabeza, Marisa; Sánchez-Márquez, Araceli; Garrido, Mariana; Silva, Aylín; Bratoeff, Eugene

2016-01-01

This article summarizes the importance of different targets such as 5α-reductase, 17β-HSD, CYP17A, androgen receptor and protein kinase A for the treatment of prostate cancer and benign prostatic hyperplasia. It is a well known fact that dihydrotestosterone (DHT) is associated with the development of androgen-dependent afflictions. At the present time, several research groups are attempting to develop new steroidal and non-steroidal molecules with the purpose of inhibiting the synthesis and biological response of DHT. This review also discusses the most recent studies reported in the literature that describe the therapeutic potential of novel compounds, as well as the new drugs, principally inhibitors of 5α-reductase. PMID:26861003

Real-time electrochemical monitoring of isothermal helicase-dependent amplification of nucleic acids.

PubMed

Kivlehan, Francine; Mavré, François; Talini, Luc; Limoges, Benoît; Marchal, Damien

2011-09-21

We described an electrochemical method to monitor in real-time the isothermal helicase-dependent amplification of nucleic acids. The principle of detection is simple and well-adapted to the development of portable, easy-to-use and inexpensive nucleic acids detection technologies. It consists of monitoring a decrease in the electrochemical current response of a reporter DNA intercalating redox probe during the isothermal DNA amplification. The method offers the possibility to quantitatively analyze target nucleic acids in less than one hour at a single constant temperature, and to perform at the end of the isothermal amplification a DNA melt curve analysis for differentiating between specific and non-specific amplifications. To illustrate the potentialities of this approach for the development of a simple, robust and low-cost instrument with high throughput capability, the method was validated with an electrochemical system capable of monitoring up to 48 real-time isothermal HDA reactions simultaneously in a disposable microplate consisting of 48-electrochemical microwells. Results obtained with this approach are comparable to that obtained with a well-established but more sophisticated and expensive fluorescence-based method. This makes for a promising alternative detection method not only for real-time isothermal helicase-dependent amplification of nucleic acid, but also for other isothermal DNA amplification strategies.

Initial community and environment determine the response of bacterial communities to dispersant and oil contamination.

PubMed

Ortmann, Alice C; Lu, YueHan

2015-01-15

Bioremediation of seawater by natural bacterial communities is one potential response to coastal oil spills, but the success of the approach may vary, depending on geographical location, oil composition and the timing of spill. The short term response of coastal bacteria to dispersant, oil and dispersed oil was characterized using 16S rRNA gene tags in two mesocosm experiments conducted two months apart. Despite differences in the amount of oil-derived alkanes across the treatments and experiments, increases in the contributions of hydrocarbon degrading taxa and decreases in common estuarine bacteria were observed in response to dispersant and/or oil. Between the two experiments, the direction and rates of changes in particulate alkane concentrations differed, as did the magnitude of the bacterial response to oil and/or dispersant. Together, our data underscore large variability in bacterial responses to hydrocarbon pollutants, implying that bioremediation success varies with starting biological and environmental conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Angle-dependent strong-field molecular ionization rates with tuned range-separated time-dependent density functional theory.

PubMed

Sissay, Adonay; Abanador, Paul; Mauger, François; Gaarde, Mette; Schafer, Kenneth J; Lopata, Kenneth

2016-09-07

Strong-field ionization and the resulting electronic dynamics are important for a range of processes such as high harmonic generation, photodamage, charge resonance enhanced ionization, and ionization-triggered charge migration. Modeling ionization dynamics in molecular systems from first-principles can be challenging due to the large spatial extent of the wavefunction which stresses the accuracy of basis sets, and the intense fields which require non-perturbative time-dependent electronic structure methods. In this paper, we develop a time-dependent density functional theory approach which uses a Gaussian-type orbital (GTO) basis set to capture strong-field ionization rates and dynamics in atoms and small molecules. This involves propagating the electronic density matrix in time with a time-dependent laser potential and a spatial non-Hermitian complex absorbing potential which is projected onto an atom-centered basis set to remove ionized charge from the simulation. For the density functional theory (DFT) functional we use a tuned range-separated functional LC-PBE*, which has the correct asymptotic 1/r form of the potential and a reduced delocalization error compared to traditional DFT functionals. Ionization rates are computed for hydrogen, molecular nitrogen, and iodoacetylene under various field frequencies, intensities, and polarizations (angle-dependent ionization), and the results are shown to quantitatively agree with time-dependent Schrödinger equation and strong-field approximation calculations. This tuned DFT with GTO method opens the door to predictive all-electron time-dependent density functional theory simulations of ionization and ionization-triggered dynamics in molecular systems using tuned range-separated hybrid functionals.

Angle-dependent strong-field molecular ionization rates with tuned range-separated time-dependent density functional theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sissay, Adonay; Abanador, Paul; Mauger, François

2016-09-07

Strong-field ionization and the resulting electronic dynamics are important for a range of processes such as high harmonic generation, photodamage, charge resonance enhanced ionization, and ionization-triggered charge migration. Modeling ionization dynamics in molecular systems from first-principles can be challenging due to the large spatial extent of the wavefunction which stresses the accuracy of basis sets, and the intense fields which require non-perturbative time-dependent electronic structure methods. In this paper, we develop a time-dependent density functional theory approach which uses a Gaussian-type orbital (GTO) basis set to capture strong-field ionization rates and dynamics in atoms and small molecules. This involves propagatingmore » the electronic density matrix in time with a time-dependent laser potential and a spatial non-Hermitian complex absorbing potential which is projected onto an atom-centered basis set to remove ionized charge from the simulation. For the density functional theory (DFT) functional we use a tuned range-separated functional LC-PBE*, which has the correct asymptotic 1/r form of the potential and a reduced delocalization error compared to traditional DFT functionals. Ionization rates are computed for hydrogen, molecular nitrogen, and iodoacetylene under various field frequencies, intensities, and polarizations (angle-dependent ionization), and the results are shown to quantitatively agree with time-dependent Schrödinger equation and strong-field approximation calculations. This tuned DFT with GTO method opens the door to predictive all-electron time-dependent density functional theory simulations of ionization and ionization-triggered dynamics in molecular systems using tuned range-separated hybrid functionals.« less

Time-dependent nonequilibrium soft x-ray response during a spin crossover

NASA Astrophysics Data System (ADS)

van Veenendaal, Michel

2018-03-01

A theoretical framework is developed for better understanding the time-dependent soft-x-ray response of dissipative quantum many-body systems. It is shown how x-ray absorption and resonant inelastic x-ray scattering (RIXS) at transition-metal L edges can provide insight into ultrafast intersystem crossings of importance for energy conversion, ultrafast magnetism, and catalysis. The photoinduced doublet-to-quartet spin crossover on cobalt in Fe-Co Prussian blue analogs is used as a model system to demonstrate how the x-ray response is affected by the nonequilibrium dynamics on a femtosecond time scale. Changes in local spin and symmetry and the underlying mechanism are reflected in strong broadenings, a collapse of clear selection rules during the intersystem crossing, fluctuations in the isotropic branching ratio in x-ray absorption, crystal-field collapse and/or oscillations, and time-dependent anti-Stokes processes in RIXS.

Sensitivity to timing and order in human visual cortex

PubMed Central

Singer, Jedediah M.; Madsen, Joseph R.; Anderson, William S.

2014-01-01

Visual recognition takes a small fraction of a second and relies on the cascade of signals along the ventral visual stream. Given the rapid path through multiple processing steps between photoreceptors and higher visual areas, information must progress from stage to stage very quickly. This rapid progression of information suggests that fine temporal details of the neural response may be important to the brain's encoding of visual signals. We investigated how changes in the relative timing of incoming visual stimulation affect the representation of object information by recording intracranial field potentials along the human ventral visual stream while subjects recognized objects whose parts were presented with varying asynchrony. Visual responses along the ventral stream were sensitive to timing differences as small as 17 ms between parts. In particular, there was a strong dependency on the temporal order of stimulus presentation, even at short asynchronies. From these observations we infer that the neural representation of complex information in visual cortex can be modulated by rapid dynamics on scales of tens of milliseconds. PMID:25429116

Characterization of a time-resolved non-contact scanning diffuse optical imaging system exploiting fast-gated single-photon avalanche diode detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Sieno, Laura, E-mail: laura.disieno@polimi.it; Dalla Mora, Alberto; Contini, Davide

2016-03-15

We present a system for non-contact time-resolved diffuse reflectance imaging, based on small source-detector distance and high dynamic range measurements utilizing a fast-gated single-photon avalanche diode. The system is suitable for imaging of diffusive media without any contact with the sample and with a spatial resolution of about 1 cm at 1 cm depth. In order to objectively assess its performances, we adopted two standardized protocols developed for time-domain brain imagers. The related tests included the recording of the instrument response function of the setup and the responsivity of its detection system. Moreover, by using liquid turbid phantoms with absorbingmore » inclusions, depth-dependent contrast and contrast-to-noise ratio as well as lateral spatial resolution were measured. To illustrate the potentialities of the novel approach, the characteristics of the non-contact system are discussed and compared to those of a fiber-based brain imager.« less

Dependence of the rate of LiF ion pairing on the description of molecular interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pluharova, Eva; Baer, Marcel D.; Schenter, Gregory K.

2016-03-03

We present an analysis of the dynamics of ion-pairing of Lithium Fluoride (LiF) in aqueous solvent using both detailed molecular simulation as well as reduced models within a Gener- alized Langevin Equation (GLE) framework. We explored the sensitivity of the ion-pairing phenomena to the details of descriptions of molecular interaction, comparing two empirical potentials to explicit quantum based density functional theory. We find quantitative differences in the potentials of mean force for ion-pairing as well as time dependent frictions that lead to variations in the rate constant and reactive flux correlation functions. These details reflect differences in solvent response tomore » ion-pairing between different representations of molecular interaction and influence anharmonicity of the dynamic response. We find that the short time anharmonic response is recovered with a GLE parameterization. Recovery of the details of long time response may require extensions to the reduced model. We show that the utility of using a reduced model leads to a straight forward application of variational transition state the- ory concepts to the condensed phase system. The significance of this is reflected in the analysis of committor distributions and the variation of planar hypersurfaces, leading to an improved understanding of factors that determine the rate of LiF ion-pairing. CJM and GKS are supported by the U.S. Department of Energy‘s (DOE) Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences. Pacific Northwest Na- tional Laboratory (PNNL) is operated for the Department of Energy by Battelle. MDB is grateful for the support of Laboratory Directed Research and Development funding under the auspices of PNNL’s Laboratory Initiative Materials Synthesis and Simulation across Scales (MS3). Additional computing resources were generously allocated by PNNL’s Institutional Computing program. EP acknowledges support from PNNL’s Alternate Sponsored Fellowship program and IMPRS Dres- den.Support to P.J. from the Czech Science Foundation (grant P208/12/G016) and the Academy of Sciences (Praemium Academie award) is gratefully acknowledged.« less

Stimulus dependent neural oscillatory patterns show reliable statistical identification of autism spectrum disorder in a face perceptual decision task.

PubMed

Castelhano, João; Tavares, Paula; Mouga, Susana; Oliveira, Guiomar; Castelo-Branco, Miguel

2018-05-01

Electroencephalographic biomarkers have been widely investigated in autism, in the search for diagnostic, prognostic and therapeutic outcome measures. Here we took advantage of the information available in temporal oscillatory patterns evoked by simple perceptual decisions to investigate whether stimulus dependent oscillatory signatures can be used as potential biomarkers in autism spectrum disorder (ASD). We studied an extensive set of stimuli (9 categories of faces) and performed data driven classification (Support vector machine, SVM) of ASD vs. Controls with features based on the EEG power responses. We carried out an extensive time-frequency and synchrony analysis of distinct face categories requiring different processing mechanisms in terms of non-holistic vs. holistic processing. We found that the neuronal oscillatory responses of low gamma frequency band, locked to photographic and abstract two-tone (Mooney) face stimulus presentation are decreased in ASD vs. the control group. We also found decreased time-frequency (TF) responses in the beta band in ASD after 350 ms, possibly related to motor preparation. On the other hand, synchrony in the 30-45 Hz band showed a distinct spatial pattern in ASD. These power changes enabled accurate classification of ASD with an SVM approach. SVM accuracy was approximately 85%. ROC curves showed about 94% AUC (area under the curve). Combination of Mooney and Photographic face stimuli evoked features enabled a better separation between groups, reaching an AUC of 98.6%. We identified a relative decrease in EEG responses to face stimuli in ASD in the beta (15-30 Hz; >350 ms) and gamma (30-45 Hz; 55-80 Hz; 50-350 ms) frequency ranges. These can be used as input of a machine learning approach to separate between groups with high accuracy. Future studies can use EEG time-frequency patterns evoked by particular types of faces as a diagnostic biomarker and potentially as outcome measures in therapeutic trials. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Reinforcement and substitution in humans: a multiple-response analysis1

PubMed Central

Bernstein, Daniel J.; Ebbesen, Ebbe B.

1978-01-01

Three adult human subjects engaged in activities such as reading, sewing, artwork, and candlemaking while living alone in a laboratory apartment 24 hours per day for several weeks. After a baseline period in which the activities were fully available, access to a particular activity (contingent response) was made dependent on engaging in another less-preferred activity (instrumental response). The contingencies produced substantial increases in instrumental responding, and responding decreased toward baseline levels when the dependency was removed. Under the contingent conditions, time earned for the concurrent activity was always less than the baseline level. To determine the contribution of this reduction to the instrumental increase, access to the contingent activity was restricted in the absence of any dependency. The results indicated that increases among responses that filled the newly available time could be selective, e.g., artwork increased when reading was restricted but candlemaking did not. It was concluded that the reductions in the contingent response that accompany contingencies usually do not exclusively determine instrumental increases, but selective increases can contribute to the increase in time devoted to the instrumental response. PMID:16812105

A Direct Screening Procedure for Gravitropism Mutants in Arabidopsis thaliana (L.) Heynh. 1

PubMed Central

Bullen, Bertha L.; Best, Thérèse R.; Gregg, Mary M.; Barsel, Sara-Ellen; Poff, Kenneth L.

1990-01-01

In order to isolate gravitropism mutants of Arabidopsis thaliana (L.) Heynh. var Estland for the genetic dissection of the gravitropism pathway, a direct screening procedure has been developed in which mutants are selected on the basis of their gravitropic response. Variability in hypocotyl curvature was dependent on the germination time of each seed stock, resulting in the incorrect identification of several lines as gravitropism mutants when a standard protocol for the potentiation of germination was used. When the protocol was adjusted to allow for differences in germination time, these lines were eliminated from the collection. Out of the 60,000 M2 seedlings screened, 0.3 to 0.4% exhibited altered gravitropism. In approximately 40% of these mutant lines, only gravitropism by the root or the hypocotyl was altered, while the response of the other organ was unaffected. These data support the hypothesis that root and hypocotyl gravitropism are genetically separable. PMID:11537704

A direct screening procedure for gravitropism mutants in Arabidopsis thaliana (L.) Heynh

NASA Technical Reports Server (NTRS)

Bullen, B. L.; Best, T. R.; Gregg, M. M.; Poff, K. L.; Barsel, S-E (Principal Investigator)

1990-01-01

In order to isolate gravitropism mutants of Arabidopsis thaliana (L.) Heynh. var Estland for the genetic dissection of the gravitropism pathway, a direct screening procedure has been developed in which mutants are selected on the basis of their gravitropic response. Variability in hypocotyl curvature was dependent on the germination time of each seed stock, resulting in the incorrect identification of several lines as gravitropism mutants when a standard protocol for the potentiation of germination was used. When the protocol was adjusted to allow for differences in germination time, these lines were eliminated from the collection. Out of the 60,000 M2 seedlings screened, 0.3 to 0.4% exhibited altered gravitropism. In approximately 40% of these mutant lines, only gravitropism by the root or the hypocotyl was altered, while the response of the other organ was unaffected. These data support the hypothesis that root and hypocotyl gravitropism are genetically separable.

Length dependence of staircase potentiation: interactions with caffeine and dantrolene sodium.

PubMed

Rassier, D E; MacIntosh, B R

2000-04-01

In skeletal muscle, there is a length dependence of staircase potentiation for which the mechanism is unclear. In this study we tested the hypothesis that abolition of this length dependence by caffeine is effected by a mechanism independent of enhanced Ca2+ release. To test this hypothesis we have used caffeine, which abolishes length dependence of potentiation, and dantrolene sodium, which inhibits Ca2+ release. In situ isometric twitch contractions of rat gastrocnemius muscle before and after 20 s of repetitive stimulation at 5 Hz were analyzed at optimal length (Lo), Lo - 10%, and Lo + 10%. Potentiation was observed to be length dependent, with an increase in developed tension (DT) of 78 +/- 12, 51 +/- 5, and 34 +/- 9% (mean +/- SEM), at Lo - 10%, Lo, and Lo + 10%, respectively. Caffeine diminished the length dependence of activation and suppressed the length dependence of staircase potentiation, giving increases in DT of 65+/-13, 53 +/- 11, and 45 +/- 12% for Lo - 10%, Lo, and Lo + 10%, respectively. Dantrolene administered after caffeine did not reverse this effect. Dantrolene alone depressed the potentiation response, but did not affect the length dependence of staircase potentiation, with increases in DT of 58 +/- 17, 26 +/- 8, and 18 +/- 7%, respectively. This study confirms that there is a length dependence of staircase potentiation in mammalian skeletal muscle which is suppressed by caffeine. Since dantrolene did not alter this suppression of the length dependence of potentiation by caffeine, it is apparently not directly modulated by Ca2+ availability in the myoplasm.

Time-dependent scattering of incident light of various wavelengths in ferrofluids under external magnetic field

NASA Astrophysics Data System (ADS)

Jin, Jingyu; Song, Dongxing; Geng, Jiafeng; Jing, Dengwei

2018-02-01

Ferrofluids can exhibit the anisotropic thermodynamic properties under magnetic fields. The dynamic optical properties of ferrofluids in the presence of magnetic fields are of particular interest due to their potential application as various optical devices. Although time-dependent light scattering by ferrofluids have been extensively studied, the effect of wavelength of incident light have been rarely considered. Here, for the first time, we investigated both the time- and wavelength-dependent light scattering in water based ferrofluids containing Fe3O4 nanoparticles under an external magnetic field. The field-induced response behavior of the prepared ferrofluid samples was determined and verified first by thermal conductivity measurement and numerical simulation. Double-beam UV-Vis spectrophotometer was employed to record the temporal evolution of transmitted intensity of incident light of various wavelengths passing through the ferrofluid sample and propagating parallel to the applied field. As expected, the light intensity decreases to a certain value right after the field is turned on due to the thermal fluctuation induced disorder inside the flexible particle chains. Then the light intensity further decreases with time until the appearance of a minimum at time τ0 followed by an inversed increase before finally reaches equilibrium at a particular time. More importantly, the characteristic inversion time τ0 was found to follow a power law increase with the wavelength of incident light (τ0 ∼ λα, where α = 2.07). A quantitative explanation for the wavelength dependence of characteristic time was proposed based on the finite-difference time-domain (FDTD) method. The simulation results are in good agreement with our experimental observations. The time-dependent light scattering in ferrofluids under different incident wavelengths was rationalized by considering both the coarsening process of the particle chains and the occurrence of resonance within the magnetic scatterers. Our finding should be of value for the development of various light-tunable optical devices.

Transcriptional dynamics with time-dependent reaction rates

NASA Astrophysics Data System (ADS)

Nandi, Shubhendu; Ghosh, Anandamohan

2015-02-01

Transcription is the first step in the process of gene regulation that controls cell response to varying environmental conditions. Transcription is a stochastic process, involving synthesis and degradation of mRNAs, that can be modeled as a birth-death process. We consider a generic stochastic model, where the fluctuating environment is encoded in the time-dependent reaction rates. We obtain an exact analytical expression for the mRNA probability distribution and are able to analyze the response for arbitrary time-dependent protocols. Our analytical results and stochastic simulations confirm that the transcriptional machinery primarily act as a low-pass filter. We also show that depending on the system parameters, the mRNA levels in a cell population can show synchronous/asynchronous fluctuations and can deviate from Poisson statistics.

Multilayer Black Phosphorus Near-Infrared Photodetectors.

PubMed

Hou, Chaojian; Yang, Lijun; Li, Bo; Zhang, Qihan; Li, Yuefeng; Yue, Qiuyang; Wang, Yang; Yang, Zhan; Dong, Lixin

2018-05-23

Black phosphorus (BP), owing to its distinguished properties, has become one of the most competitive candidates for photodetectors. However, there has been little attention paid on photo-response performance of multilayer BP nanoflakes with large layer thickness. In fact, multilayer BP nanoflakes with large layer thickness have greater potential from the fabrication viewpoint as well as due to the physical properties than single or few layer ones. In this report, the thickness-dependence of the intrinsic property of BP photodetectors in the dark was initially investigated. Then the photo-response performance (including responsivity, photo-gain, photo-switching time, noise equivalent power, and specific detectivity) of BP photodetectors with relative thicker thickness was explored under a near-infrared laser beam ( λ IR = 830 nm). Our experimental results reveal the impact of BP's thickness on the current intensity of the channel and show degenerated p-type BP is beneficial for larger current intensity. More importantly, the photo-response of our thicker BP photodetectors exhibited a larger responsivity up to 2.42 A/W than the few-layer ones and a fast response photo-switching speed (response time is ~2.5 ms) comparable to thinner BP nanoflakes was obtained, indicating BP nanoflakes with larger layer thickness are also promising for application for ultra-fast and ultra-high near-infrared photodetectors.

Preferential inhibition of Ih in rat trigeminal ganglion neurons by an organic blocker.

PubMed

Janigro, D; Martenson, M E; Baumann, T K

1997-11-15

The potency and specificity of a novel organic Ih current blocker DK-AH 268 (DK, Boehringer) was studied in cultured rat trigeminal ganglion neurons using whole-cell patch-clamp recording techniques. In neurons current-clamped at the resting potential, the application of 10 microM DK caused a slight hyperpolarization of the membrane potential and a small increase in the threshold for action potential discharge without any major change in the shape of the action potential. In voltage-clamped neurons, DK caused a reduction of a hyperpolarization-activated current. Current subtraction protocols revealed that the time-dependent, hyperpolarization-activated currents blocked by 10 microM DK or external Cs+ (3 mM) had virtually identical activation properties, suggesting that DK and Cs+ caused blockade of the same current, namely Ih. The block of Ih by DK was dose-dependent. At the intermediate and higher concentrations of DK (10 and 100 microM) a decrease in specificity was observed so that time-independent, inwardly rectifying and noninactivating, voltage-gated outward potassium currents were also reduced by DK but to a much lesser extent than the time-dependent, hyperpolarization-activated currents. Blockade of the time-dependent, hyperpolarization-activated currents by DK appeared to be use-dependent since it required hyperpolarization for the effect to take place. Relief of DK block was also aided by membrane hyperpolarization. Since both the time-dependent current blocked by DK and the Cs+-sensitive time-dependent current behaved as Ih, we conclude that 10 microM DK can preferentially reduce Ih without a major effect on other potassium currents. Thus, DK may be a useful agent in the investigation of the function of Ih in neurons.

Experimental measurements of the SP response to concentration and temperature gradients in sandstones with application to subsurface geophysical monitoring

NASA Astrophysics Data System (ADS)

Leinov, E.; Jackson, M. D.

2014-09-01

Exclusion-diffusion potentials arising from temperature gradients are widely neglected in self-potential (SP) surveys, despite the ubiquitous presence of temperature gradients in subsurface settings such as volcanoes and hot springs, geothermal fields, and oil reservoirs during production via water or steam injection. Likewise, with the exception of borehole SP logging, exclusion-diffusion potentials arising from concentration gradients are also neglected or, at best, it is assumed that the diffusion potential dominates. To better interpret these SP sources requires well-constrained measurements of the various coupling terms. We report measurements of thermoelectric and electrochemical exclusion-diffusion potentials across sandstones saturated with NaCl brine and find that electrode effects can dominate the measured voltage. After correcting for these, we find that Hittorf transport numbers are the same within experimental error regardless of whether ion transport occurs in response to temperature or concentration gradients over the range of NaCl concentration investigated that is typical of natural systems. Diffusion potentials dominate only if the pore throat radius is more than approximately 4000 times larger than the diffuse layer thickness. In fine-grained sandstones with small pore throat diameter, this condition is likely to be met only if the saturating brine is of relatively high salinity; thus, in many cases of interest to earth scientists, exclusion-diffusion potentials will comprise significant contributions from both ionic diffusion through, and ionic exclusion from, the pore space of the rock. However, in coarse-grained sandstones, or sandstones saturated with high-salinity brine, exclusion-diffusion potentials can be described using end-member models in which ionic exclusion is neglected. Exclusion-diffusion potentials in sandstones depend upon pore size and salinity in a complex way: they may be positive, negative, or zero depending upon sandstone rock texture (expressed here by the pore radius r) and salinity.

Dependence of trends in and sensitivity of drought over China (1961-2013) on potential evaporation model

NASA Astrophysics Data System (ADS)

Zhang, Jie; Sun, Fubao; Xu, Jijun; Chen, Yaning; Sang, Yan-Fang; Liu, Changming

2016-01-01

The Palmer Drought Severity Index (PDSI) can lead to controversial results in assessing droughts responding to global warming. Here we assess recent changes in the droughts over China (1961-2013) using the PDSI with two different estimates, i.e., the Thornthwaite (PDSI_th) and Penman-Monteith (PDSI_pm) approaches. We found that droughts have become more severe in the PDSI_th but slightly lessened in the PDSI_pm estimate. To quantify and interpret the different responses in the PDSI_th and PDSI_pm, we designed numerical experiments and found that drying trend of the PDSI_th responding to the warming alone is 3.4 times higher than that of the PDSI_pm, and the latter was further compensated by decreases in wind speed and solar radiation causing the slightly wetting in the PDSI_pm. Interestingly, we found that interbasin difference in the PDSI_th and PDSI_pm responses to the warming alone tends to be larger in warmer basins, exponentially depending on mean temperature.

Chiral tunneling modulated by a time-periodic potential on the surface states of a topological insulator

PubMed Central

Li, Yuan; Jalil, Mansoor B. A.; Tan, S. G.; Zhao, W.; Bai, R.; Zhou, G. H.

2014-01-01

Time-periodic perturbation can be used to modify the transport properties of the surface states of topological insulators, specifically their chiral tunneling property. Using the scattering matrix method, we study the tunneling transmission of the surface states of a topological insulator under the influence of a time-dependent potential and finite gate bias voltage. It is found that perfect transmission is obtained for electrons which are injected normally into the time-periodic potential region in the absence of any bias voltage. However, this signature of Klein tunneling is destroyed when a bias voltage is applied, with the transmission probability of normally incident electrons decreasing with increasing gate bias voltage. Likewise, the overall conductance of the system decreases significantly when a gate bias voltage is applied. The characteristic left-handed helicity of the transmitted spin polarization is also broken by the finite gate bias voltage. In addition, the time-dependent potential modifies the large-angle transmission profile, which exhibits an oscillatory or resonance-like behavior. Finally, time-dependent transport modes (with oscillating potential in the THz frequency) can result in enhanced overall conductance, irrespective of the presence or absence of the gate bias voltage. PMID:24713634

Biophysical characterization and functional consequences of a slowly inactivating potassium current in neostriatal neurons.

PubMed

Gabel, L A; Nisenbaum, E S

1998-04-01

Neostriatal spiny projection neurons can display a pronounced delay in their transition to action potential discharge that is mediated by a slowly developing ramp depolarization. The possible contribution of a slowly inactivating A-type K+ current (IAs) to this delayed excitation was investigated by studying the biophysical and functional properties of IAs using whole cell voltage- and current-clamp recording from acutely isolated neostriatal neurons. Isolation of IAs from other voltage-gated, calcium-independent K+ currents was achieved through selective blockade of IAs with low concentrations (10 microM) of the benzazepine derivative, 6-chloro-7,8-dihydroxy-3-allyl- 1-phenyl-2,3,4,5-tetra-hydro-1H-3-benzazepine (APB; SKF82958) and subsequent current subtraction. Examination of the voltage dependence of activation showed that IAs began to flow at approximately -60 mV in response to depolarization. The voltage dependence of inactivation revealed that approximately 50% of IAs channels were available at the normal resting potential (-80 mV) of these cells, but that only 20% of the channels were available at membrane potentials corresponding to spike threshold (about -40 mV). At these depolarized membrane potentials, the rate of activation was moderately rapid (tau approximately 60 ms), whereas the rate of inactivation was slow (tau approximately 1.5 s). The time course of removal of inactivation of IAs at -80 mV also was relatively slow (tau approximately 1.0 s). The subthreshold availability of IAs combined with its rapid activation and slow inactivation rates suggested that this current should be capable of dampening the onset of prolonged depolarizing responses, but over time its efficacy should diminish, slowly permitting the membrane to depolarize toward spike threshold. Voltage recording experiments confirmed this hypothesis by demonstrating that application of APB at a concentration (10 microM) that selectively blocks IAs substantially decreased the latency to discharge and increased the frequency of firing of neostriatal neurons. The properties of IAs suggest that it should play a critical role in placing the voltage limits on the recurring episodes of subthreshold depolarization which are characteristic of spiny neurons recorded in vivo. However, the voltage dependence and recovery kinetics of inactivation of IAs predict that its effectiveness will vary exponentially with the level and duration of hyperpolarization which precedes depolarizing episodes. Thus long periods of hyperpolarization should increase the availability of IAs and dampen succeeding depolarizations; whereas brief epochs of hyperpolarization should not sufficiently remove inactivation of IAs, thereby reducing its ability to limit subsequent depolarizing responses.

RNA-Seq Analysis of Microglia Reveals Time-Dependent Activation of Specific Genetic Programs following Spinal Cord Injury

PubMed Central

Noristani, Harun N.; Gerber, Yannick N.; Sabourin, Jean-Charles; Le Corre, Marine; Lonjon, Nicolas; Mestre-Frances, Nadine; Hirbec, Hélène E.; Perrin, Florence E.

2017-01-01

Neurons have inherent competence to regrow following injury, although not spontaneously. Spinal cord injury (SCI) induces a pronounced neuroinflammation driven by resident microglia and infiltrating peripheral macrophages. Microglia are the first reactive glial population after SCI and participate in recruitment of monocyte-derived macrophages to the lesion site. Both positive and negative influence of microglia and macrophages on axonal regeneration had been reported after SCI, raising the issue whether their response depends on time post-lesion or different lesion severity. We analyzed molecular alterations in microglia at several time-points after different SCI severities using RNA-sequencing. We demonstrate that activation of microglia is time-dependent post-injury but is independent of lesion severity. Early transcriptomic response of microglia after SCI involves proliferation and neuroprotection, which is then switched to neuroinflammation at later stages. Moreover, SCI induces an autologous microglial expression of astrocytic markers with over 6% of microglia expressing glial fibrillary acidic protein and vimentin from as early as 72 h post-lesion and up to 6 weeks after injury. We also identified the potential involvement of DNA damage and in particular tumor suppressor gene breast cancer susceptibility gene 1 (Brca1) in microglia after SCI. Finally, we established that BRCA1 protein is specifically expressed in non-human primate spinal microglia and is upregulated after SCI. Our data provide the first transcriptomic analysis of microglia at multiple stages after different SCI severities. Injury-induced microglia expression of astrocytic markers at RNA and protein levels demonstrates novel insights into microglia plasticity. Finally, increased microglia expression of BRCA1 in rodents and non-human primate model of SCI, suggests the involvement of oncogenic proteins after CNS lesion. PMID:28420963

Thermal Density Functional Theory: Time-Dependent Linear Response and Approximate Functionals from the Fluctuation-Dissipation Theorem

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pribram-Jones, Aurora; Grabowski, Paul E.; Burke, Kieron

We present that the van Leeuwen proof of linear-response time-dependent density functional theory (TDDFT) is generalized to thermal ensembles. This allows generalization to finite temperatures of the Gross-Kohn relation, the exchange-correlation kernel of TDDFT, and fluctuation dissipation theorem for DFT. Finally, this produces a natural method for generating new thermal exchange-correlation approximations.

Thermal Density Functional Theory: Time-Dependent Linear Response and Approximate Functionals from the Fluctuation-Dissipation Theorem

DOE PAGES

Pribram-Jones, Aurora; Grabowski, Paul E.; Burke, Kieron

2016-06-08

We present that the van Leeuwen proof of linear-response time-dependent density functional theory (TDDFT) is generalized to thermal ensembles. This allows generalization to finite temperatures of the Gross-Kohn relation, the exchange-correlation kernel of TDDFT, and fluctuation dissipation theorem for DFT. Finally, this produces a natural method for generating new thermal exchange-correlation approximations.

Brain potentials measured during a Go/NoGo task predict completion of substance abuse treatment.

PubMed

Steele, Vaughn R; Fink, Brandi C; Maurer, J Michael; Arbabshirani, Mohammad R; Wilber, Charles H; Jaffe, Adam J; Sidz, Anna; Pearlson, Godfrey D; Calhoun, Vince D; Clark, Vincent P; Kiehl, Kent A

2014-07-01

U.S. nationwide estimates indicate that 50% to 80% of prisoners have a history of substance abuse or dependence. Tailoring substance abuse treatment to specific needs of incarcerated individuals could improve effectiveness of treating substance dependence and preventing drug abuse relapse. We tested whether pretreatment neural measures of a response inhibition (Go/NoGo) task would predict which individuals would or would not complete a 12-week cognitive behavioral substance abuse treatment program. Adult incarcerated participants (n = 89; women n = 55) who volunteered for substance abuse treatment performed a Go/NoGo task while event-related potentials (ERPs) were recorded. Stimulus- and response-locked ERPs were compared between participants who completed (n = 68; women = 45) and discontinued (n = 21; women = 10) treatment. As predicted, stimulus-locked P2, response-locked error-related negativity (ERN/Ne), and response-locked error positivity (Pe), measured with windowed time-domain and principal component analysis, differed between groups. Using logistic regression and support-vector machine (i.e., pattern classifiers) models, P2 and Pe predicted treatment completion above and beyond other measures (i.e., N2, P300, ERN/Ne, age, sex, IQ, impulsivity, depression, anxiety, motivation for change, and years of drug abuse). Participants who discontinued treatment exhibited deficiencies in sensory gating, as indexed by smaller P2; error-monitoring, as indexed by smaller ERN/Ne; and adjusting response strategy posterror, as indexed by larger Pe. The combination of P2 and Pe reliably predicted 83.33% of individuals who discontinued treatment. These results may help in the development of individualized therapies, which could lead to more favorable, long-term outcomes. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

Brain Potentials Measured During a Go/NoGo Task Predict Completion of Substance Abuse Treatment

PubMed Central

Steele, Vaughn R.; Fink, Brandi C.; Maurer, J. Michael; Arbabshirani, Mohammad R.; Wilber, Charles H.; Jaffe, Adam J.; Sidz, Anna; Pearlson, Godfrey D.; Calhoun, Vince D.; Clark, Vincent P.; Kiehl, Kent A.

2014-01-01

Background US nationwide estimates indicate 50–80% of prisoners have a history of substance abuse or dependence. Tailoring substance abuse treatment to specific needs of incarcerated individuals could improve effectiveness of treating substance dependence and preventing drug abuse relapse. The purpose of the present study was to test the hypothesis that pre-treatment neural measures of a Go/NoGo task would predict which individuals would or would not complete a 12-week cognitive behavioral substance abuse treatment program. Methods Adult incarcerated participants (N=89; Females=55) who volunteered for substance abuse treatment performed a response inhibition (Go/NoGo) task while event-related potentials (ERP) were recorded. Stimulus- and response-locked ERPs were compared between individuals who completed (N=68; Females=45) and discontinued (N=21; Females=10) treatment. Results As predicted, stimulus-locked P2, response-locked error-related negativity (ERN/Ne), and response-locked error positivity (Pe), measured with windowed time-domain and principal component analysis, differed between groups. Using logistic regression and support-vector machine (i.e., pattern classifiers) models, P2 and Pe predicted treatment completion above and beyond other measures (i.e., N2, P300, ERN/Ne, age, sex, IQ, impulsivity, and self-reported depression, anxiety, motivation for change, and years of drug abuse). Conclusions We conclude individuals who discontinue treatment exhibited deficiencies in sensory gating, as indexed by smaller P2, error-monitoring, as indexed by smaller ERN/Ne, and adjusting response strategy post-error, as indexed by larger Pe. However, the combination of P2 and Pe reliably predicted 83.33% of individuals who discontinued treatment. These results may help in the development of individualized therapies, which could lead to more favorable, long-term outcomes. PMID:24238783

DEVELOPMENT AND PEER REVIEW OF TIME-TO-EFFECT MODELS FOR THE ANALYSIS OF NEUROTOXICITY AND OTHER TIME DEPENDENT DATA

EPA Science Inventory

Neurobehavioral studies pose unique challenges for dose-response modeling, including small sample size and relatively large intra-subject variation, repeated measurements over time, multiple endpoints with both continuous and ordinal scales, and time dependence of risk characteri...

Dependence of Ca outflow and depression of frog myocardium contraction on ryodipine concentration.

PubMed

Narusevicius, E; Gendviliene, V; Macianskiene, R; Hmelj-Dunai, G; Velena, A; Duburs, G

1988-02-01

The effect of ryodipine on calcium outflow from tissues, on contraction force, the duration of action potentials and the relaxation phase time-constant in the contraction cycles of myocardial strips was studied using frog heart preparations. It was found that calcium outflow (delta Ca) as a function on ryodipine concentration can be represented as: (formula; see text) A linear correlation exists between Ca2+, contraction blocking and the shortening of the action potential in the presence of various ryodipine concentrations. Ryodipine (10(-5) mol/l) decreased the relaxation time-constant by about 20% as compared to controls. It was concluded that calcium outflow from myocardial tissues in response to ryodipine is due to blockade of calcium entry into the cells and their output through the Na+--Ca2+ exchange system. Frog heart myocardial contractions are essentially under the control of calcium entry through sarcolemmal calcium channels.

Dynamical generation of Floquet Majorana flat bands in s-wave superconductors

NASA Astrophysics Data System (ADS)

Poudel, A.; Ortiz, G.; Viola, L.

2015-04-01

We present quantum control techniques to engineer flat bands of symmetry-protected Majorana edge modes in s-wave superconductors. Specifically, we show how periodic control may be employed for designing time-independent effective Hamiltonians, which support Floquet Majorana flat bands, starting from equilibrium conditions that are either topologically trivial or only support a Majorana pair per edge. In the first approach, a suitable modulation of the chemical potential simultaneously induces Majorana flat bands and dynamically activates a pre-existing chiral symmetry which is responsible for their protection. In the second approach, the application of effective parity kicks dynamically generates a desired chiral symmetry by suppressing chirality-breaking terms in the static Hamiltonian. Our results demonstrate how the use of time-dependent control enlarges the range of possibilities for realizing gapless topological superconductivity, potentially enabling access to topological states of matter that have no known equilibrium counterpart.

Air density dependence of the response of the PTW SourceCheck 4pi ionization chamber for 125I brachytherapy seeds.

PubMed

Torres Del Río, J; Tornero-López, A M; Guirado, D; Pérez-Calatayud, J; Lallena, A M

2017-06-01

To analyze the air density dependence of the response of the new SourceCheck 4pi ionization chamber, manufactured by PTW. The air density dependence of three different SourceCheck 4pi chambers was studied by measuring 125 I sources. Measurements were taken by varying the pressure from 746.6 to 986.6hPa in a pressure chamber. Three different HDR 1000 Plus ionization chambers were also analyzed under similar conditions. A linear and a potential-like function of the air density were fitted to experimental data and their achievement in describing them was analyzed. SourceCheck 4pi chamber response showed a residual dependence on the air density once the standard pressure and temperature factor was applied. The chamber response was overestimated when the air density was below that under normal atmospheric conditions. A similar dependence was found for the HDR 1000 Plus chambers analyzed. A linear function of the air density permitted a very good description of this residual dependence, better than with a potential function. No significant variability between the different specimens of the same chamber model studied was found. The effect of overestimation observed in the chamber responses once they are corrected for the standard pressure and temperature may represent a non-negligible ∼4% overestimation in high altitude cities as ours (700m AMSL). This overestimation behaves linearly with the air density in all cases analyzed. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Premature infants display increased noxious-evoked neuronal activity in the brain compared to healthy age-matched term-born infants.

PubMed

Slater, Rebeccah; Fabrizi, Lorenzo; Worley, Alan; Meek, Judith; Boyd, Stewart; Fitzgerald, Maria

2010-08-15

This study demonstrates that infants who are born prematurely and who have experienced at least 40days of intensive or special care have increased brain neuronal responses to noxious stimuli compared to healthy newborns at the same postmenstrual age. We have measured evoked potentials generated by noxious clinically-essential heel lances in infants born at term (8 infants; born 37-40weeks) and in infants born prematurely (7 infants; born 24-32weeks) who had reached the same postmenstrual age (mean age at time of heel lance 39.2+/-1.2weeks). These noxious-evoked potentials are clearly distinguishable from shorter latency potentials evoked by non-noxious tactile sensory stimulation. While the shorter latency touch potentials are not dependent on the age of the infant at birth, the noxious-evoked potentials are significantly larger in prematurely-born infants. This enhancement is not associated with specific brain lesions but reflects a functional change in pain processing in the brain that is likely to underlie previously reported changes in pain sensitivity in older ex-preterm children. Our ability to quantify and measure experience-dependent changes in infant cortical pain processing will allow us to develop a more rational approach to pain management in neonatal intensive care. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Anisotropic Broadband Photoresponse of Layered Type-II Weyl Semimetal MoTe2.

PubMed

Lai, Jiawei; Liu, Xin; Ma, Junchao; Wang, Qinsheng; Zhang, Kenan; Ren, Xiao; Liu, Yinan; Gu, Qiangqiang; Zhuo, Xiao; Lu, Wei; Wu, Yang; Li, Yuan; Feng, Ji; Zhou, Shuyun; Chen, Jian-Hao; Sun, Dong

2018-05-01

Photodetectors based on Weyl semimetal promise extreme performance in terms of highly sensitive, broadband and self-powered operation owing to its extraordinary material properties. Layered Type-II Weyl semimetal that break Lorentz invariance can be further integrated with other two-dimensional materials to form van der Waals heterostructures and realize multiple functionalities inheriting the advantages of other two-dimensional materials. Herein, we report the realization of a broadband self-powered photodetector based on Type-II Weyl semimetal T d -MoTe 2 . The prototype metal-MoTe 2 -metal photodetector exhibits a responsivity of 0.40 mA W -1 and specific directivity of 1.07 × 10 8 Jones with 43 μs response time at 532 nm. Broadband responses from 532 nm to 10.6 μm are experimentally tested with a potential detection range extendable to far-infrared and terahertz. Furthermore, we identify the response of the detector is polarization angle sensitive due to the anisotropic response of MoTe 2 . The anisotropy is found to be wavelength dependent, and the degree of anisotropy increases as the excitation wavelength gets closer to the Weyl nodes. In addition, with power and temperature dependent photoresponse measurements, the photocurrent generation mechanisms are investigated. Our results suggest this emerging class of materials can be harnessed for broadband angle sensitive, self-powered photodetection with decent responsivities. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lateral parabrachial nucleus mediates shortening of expiration during hypoxia.

PubMed

Song, Gang; Poon, Chi-Sang

2009-01-01

Acute hypoxia elicits complex time-dependent responses including rapid augmentation of inspiratory drive, shortening of inspiratory and expiratory durations (T(I), T(E)), and short-term potentiation and depression. The central pathways mediating these varied effects are largely unknown. Here, we show that the lateral parabrachial nucleus (LPBN) of the dorsolateral pons specifically mediates T(E)-shortening during hypoxia and not other hypoxic response components. Twelve urethane-anesthetized and vagotomized adult Sprague-Dawley rats were exposed to 1-min poikilocapnic hypoxia before and after unilateral kainic acid or bilateral electrolytic lesioning of the LPBN. Bilateral lesions resulted in a significant increase in baseline T(E) under hyperoxia. After unilateral or bilateral lesions, the decrease in T(E) during hypoxia was markedly attenuated without appreciable changes in all other hypoxic response components. These findings add to the mounting evidence that the central processing of peripheral chemoafferent inputs is segregated into parallel integrator and differentiator (low-pass and high-pass filter) pathways that separately modulate inspiratory drive, T(I), T(E) and resultant short-term potentiation and depression.

Neural decoding with kernel-based metric learning.

PubMed

Brockmeier, Austin J; Choi, John S; Kriminger, Evan G; Francis, Joseph T; Principe, Jose C

2014-06-01

In studies of the nervous system, the choice of metric for the neural responses is a pivotal assumption. For instance, a well-suited distance metric enables us to gauge the similarity of neural responses to various stimuli and assess the variability of responses to a repeated stimulus-exploratory steps in understanding how the stimuli are encoded neurally. Here we introduce an approach where the metric is tuned for a particular neural decoding task. Neural spike train metrics have been used to quantify the information content carried by the timing of action potentials. While a number of metrics for individual neurons exist, a method to optimally combine single-neuron metrics into multineuron, or population-based, metrics is lacking. We pose the problem of optimizing multineuron metrics and other metrics using centered alignment, a kernel-based dependence measure. The approach is demonstrated on invasively recorded neural data consisting of both spike trains and local field potentials. The experimental paradigm consists of decoding the location of tactile stimulation on the forepaws of anesthetized rats. We show that the optimized metrics highlight the distinguishing dimensions of the neural response, significantly increase the decoding accuracy, and improve nonlinear dimensionality reduction methods for exploratory neural analysis.

Tunneling of heat: Beyond linear response regime

NASA Astrophysics Data System (ADS)

Walczak, Kamil; Saroka, David

2018-02-01

We examine nanoscale processes of heat (energy) transfer as carried by electrons tunneling via potential barriers and molecular interconnects between two heat reservoirs (thermal baths). For that purpose, we use Landauer-type formulas to calculate thermal conductance and quadratic correction to heat flux flowing via quantum systems. As an input, we implement analytical expressions for transmission functions related to simple potential barriers and atomic bridges. Our results are discussed with respect to energy of tunneling electrons, temperature, the presence of resonant states, and specific parameters characterizing potential barriers as well as heat carriers. The simplicity of semi-analytical models developed by us allows to fit experimental data and extract crucial information about the values of model parameters. Further investigations are expected for more realistic transmission functions, while time-dependent aspects of nanoscale heat transfer may be addressed by using the concept of wave packets scattered on potential barriers and point-like defects within regular (periodic) nanostructures.

Automatic classification of visual evoked potentials based on wavelet decomposition

NASA Astrophysics Data System (ADS)

Stasiakiewicz, Paweł; Dobrowolski, Andrzej P.; Tomczykiewicz, Kazimierz

2017-04-01

Diagnosis of part of the visual system, that is responsible for conducting compound action potential, is generally based on visual evoked potentials generated as a result of stimulation of the eye by external light source. The condition of patient's visual path is assessed by set of parameters that describe the time domain characteristic extremes called waves. The decision process is compound therefore diagnosis significantly depends on experience of a doctor. The authors developed a procedure - based on wavelet decomposition and linear discriminant analysis - that ensures automatic classification of visual evoked potentials. The algorithm enables to assign individual case to normal or pathological class. The proposed classifier has a 96,4% sensitivity at 10,4% probability of false alarm in a group of 220 cases and area under curve ROC equals to 0,96 which, from the medical point of view, is a very good result.

Antecedent Moisture and Biological Inertia as Predictors of Plant and Ecosystem Productivity in Arid and Semiarid Systems

NASA Astrophysics Data System (ADS)

Ogle, K.

2011-12-01

Many plant and ecosystem processes in arid and semiarid systems may be affected by antecedent environmental conditions (e.g., precipitation patterns, soil water availability, temperature) that integrate over past days, weeks, months, seasons, or years. However, the importance of such antecedent exogenous effects relative to conditions occurring at the time of the observed process is relatively unexplored. Even less is known about the potential importance of antecedent endogenous effects that describe the influence of past ecosystem states on the current ecosystem state; e.g., how is current ecosystem productivity related to past productivity patterns? We hypothesize that incorporation of antecedent exogenous and endogenous factors can improve our predictive understanding of many plant and ecosystem processes, especially in arid and semiarid ecosystems. Furthermore, the common approach to quantifying the effects of antecedent (exogenous) variables relies on arbitrary, deterministic definitions of antecedent variables that (1) may not accurately describe the role of antecedent conditions and (2) ignore uncertainty associated with applying deterministic definitions. In this study, we employ a stochastic framework for (1) computing the antecedent variables that estimates the relative importance of conditions experienced each time unit into the past, also providing insight into potential lag responses, and (2) estimating the effect of antecedent factors on the response variable of interest. We employ this approach to explore the potential roles of antecedent exogenous and endogenous influences in three settings that illustrate the: (1) importance of antecedent precipitation for net primary productivity in the shortgrass steppe in northern Colorado, (2) dependency of tree growth on antecedent precipitation and past growth states for pinyon growing in western Colorado, and (3) influence of antecedent soil water and prior root status on observed root growth in the Mojave Desert FACE experiment. All three examples suggest that antecedent conditions are critical to predicting different indices of productivity such that the incorporation of antecedent effects explained an additional 20-40% of the variation in the productivity responses. Antecedent endogenous factors were important for understanding tree and root growth, suggesting a potential biological inertia effect that is likely linked to labile carbon storage and allocation strategies. The role of antecedent exogenous (water) variables suggests a lag response whose duration and timing differs according to the time scale of the response variable. In summary, antecedent water availability and past endogenous states appear critical to understanding plant and ecosystem productivity in arid and semiarid systems, and this study describes a stochastic framework for quantifying the potential influence of such antecedent conditions.

Phase space explorations in time dependent density functional theory

NASA Astrophysics Data System (ADS)

Rajam, Aruna K.

Time dependent density functional theory (TDDFT) is one of the useful tools for the study of the dynamic behavior of correlated electronic systems under the influence of external potentials. The success of this formally exact theory practically relies on approximations for the exchange-correlation potential which is a complicated functional of the co-ordinate density, non-local in space and time. Adiabatic approximations (such as ALDA), which are local in time, are most commonly used in the increasing applications of the field. Going beyond ALDA, has been proved difficult leading to mathematical inconsistencies. We explore the regions where the theory faces challenges, and try to answer some of them via the insights from two electron model systems. In this thesis work we propose a phase-space extension of the TDDFT. We want to answer the challenges the theory is facing currently by exploring the one-body phase-space. We give a general introduction to this theory and its mathematical background in the first chapter. In second chapter, we carryout a detailed study of instantaneous phase-space densities and argue that the functionals of distributions can be a better alternative to the nonlocality issue of the exchange-correlation potentials. For this we study in detail the interacting and the non-interacting phase-space distributions for Hookes atom model. The applicability of ALDA-based TDDFT for the dynamics in strongfields can become severely problematic due to the failure of single-Slater determinant picture.. In the third chapter, we analyze how the phase-space distributions can shine some light into this problem. We do a comparative study of Kohn-Sham and interacting phase-space and momentum distributions for single ionization and double ionization systems. Using a simple model of two-electron systems, we have showed that the momentum distribution computed directly from the exact KS system contains spurious oscillations: a non-classical description of the essentially classical two-electron dynamics. In Time dependent density matrix functional theory (TDDMFT), the evolution scheme of the 1RDM (first order reduced density matrix) contains second-order reduced density matrix (2RDM), which has to be expressed in terms of 1RDMs. Any non-correlated approximations (Hartree-Fock) for 2RDM would fail to capture the natural occupations of the system. In our fourth chapter, we show that by applying the quasi-classical and semi-classical approximations one can capture the natural occupations of the excited systems. We study a time-dependent Moshinsky atom model for this. The fifth chapter contains a comparative work on the existing non-local exchange-correlation kernels that are based on current density response frame work and the co-moving frame work. We show that the two approaches though coinciding with each other in linear response regime, actually turn out to be different in non-linear regime.

Microplastic Size-Dependent Toxicity, Oxidative Stress Induction, and p-JNK and p-p38 Activation in the Monogonont Rotifer (Brachionus koreanus).

PubMed

Jeong, Chang-Bum; Won, Eun-Ji; Kang, Hye-Min; Lee, Min-Chul; Hwang, Dae-Sik; Hwang, Un-Ki; Zhou, Bingsheng; Souissi, Sami; Lee, Su-Jae; Lee, Jae-Seong

2016-08-16

In this study, we evaluated accumulation and adverse effects of ingestion of microplastics in the monogonont rotifer (Brachionus koreanus). The dependence of microplastic toxicity on particle size was investigated by measuring several in vivo end points and studying the ingestion and egestion using 0.05-, 0.5-, and 6-μm nonfunctionalized polystyrene microbeads. To identify the defense mechanisms activated in response to microplastic exposure, the activities of several antioxidant-related enzymes and the phosphorylation status of mitogen-activated protein kinases (MAPKs) were determined. Exposure to polystyrene microbeads of all sizes led to significant size-dependent effects, including reduced growth rate, reduced fecundity, decreased lifespan and longer reproduction time. Rotifers exposed to 6-μm fluorescently labeled microbeads exhibited almost no fluorescence after 24 h, while rotifers exposed to 0.05- and 0.5-μm fluorescently labeled microbeads displayed fluorescence until 48 h, suggesting that 6-μm microbeads are more effectively egested from B. koreanus than 0.05- or 0.5-μm microbeads. This observation provides a potential explanation for our findings that microbead toxicity was size-dependent and smaller microbeads were more toxic. In vitro tests revealed that antioxidant-related enzymes and MAPK signaling pathways were significantly activated in response to microplastic exposure in a size-dependent manner.

UV Light Potentiates STING (Stimulator of Interferon Genes)-dependent Innate Immune Signaling through Deregulation of ULK1 (Unc51-like Kinase 1)*

PubMed Central

Kemp, Michael G.; Lindsey-Boltz, Laura A.; Sancar, Aziz

2015-01-01

The mechanism by which ultraviolet (UV) wavelengths of sunlight trigger or exacerbate the symptoms of the autoimmune disorder lupus erythematosus is not known but may involve a role for the innate immune system. Here we show that UV radiation potentiates STING (stimulator of interferon genes)-dependent activation of the immune signaling transcription factor interferon regulatory factor 3 (IRF3) in response to cytosolic DNA and cyclic dinucleotides in keratinocytes and other human cells. Furthermore, we find that modulation of this innate immune response also occurs with UV-mimetic chemical carcinogens and in a manner that is independent of DNA repair and several DNA damage and cell stress response signaling pathways. Rather, we find that the stimulation of STING-dependent IRF3 activation by UV is due to apoptotic signaling-dependent disruption of ULK1 (Unc51-like kinase 1), a pro-autophagic protein that negatively regulates STING. Thus, deregulation of ULK1 signaling by UV-induced DNA damage may contribute to the negative effects of sunlight UV exposure in patients with autoimmune disorders. PMID:25792739

Enduring critical period plasticity visualized by transcranial flavoprotein imaging in mouse primary visual cortex.

PubMed

Tohmi, Manavu; Kitaura, Hiroki; Komagata, Seiji; Kudoh, Masaharu; Shibuki, Katsuei

2006-11-08

Experience-dependent plasticity in the visual cortex was investigated using transcranial flavoprotein fluorescence imaging in mice anesthetized with urethane. On- and off-responses in the primary visual cortex were elicited by visual stimuli. Fluorescence responses and field potentials elicited by grating patterns decreased similarly as contrasts of visual stimuli were reduced. Fluorescence responses also decreased as spatial frequency of grating stimuli increased. Compared with intrinsic signal imaging in the same mice, fluorescence imaging showed faster responses with approximately 10 times larger signal changes. Retinotopic maps in the primary visual cortex and area LM were constructed using fluorescence imaging. After monocular deprivation (MD) of 4 d starting from postnatal day 28 (P28), deprived eye responses were suppressed compared with nondeprived eye responses in the binocular zone but not in the monocular zone. Imaging faithfully recapitulated a critical period for plasticity with maximal effects of MD observed around P28 and not in adulthood even under urethane anesthesia. Visual responses were compared before and after MD in the same mice, in which the skull was covered with clear acrylic dental resin. Deprived eye responses decreased after MD, whereas nondeprived eye responses increased. Effects of MD during a critical period were tested 2 weeks after reopening of the deprived eye. Significant ocular dominance plasticity was observed in responses elicited by moving grating patterns, but no long-lasting effect was found in visual responses elicited by light-emitting diode light stimuli. The present results indicate that transcranial flavoprotein fluorescence imaging is a powerful tool for investigating experience-dependent plasticity in the mouse visual cortex.

Detecting Moving Targets by Use of Soliton Resonances

NASA Technical Reports Server (NTRS)

Zak, Michael; Kulikov, Igor

2003-01-01

A proposed method of detecting moving targets in scenes that include cluttered or noisy backgrounds is based on a soliton-resonance mathematical model. The model is derived from asymptotic solutions of the cubic Schroedinger equation for a one-dimensional system excited by a position-and-time-dependent externally applied potential. The cubic Schroedinger equation has general significance for time-dependent dispersive waves. It has been used to approximate several phenomena in classical as well as quantum physics, including modulated beams in nonlinear optics, and superfluids (in particular, Bose-Einstein condensates). In the proposed method, one would take advantage of resonant interactions between (1) a soliton excited by the position-and-time-dependent potential associated with a moving target and (2) eigen-solitons, which represent dispersive waves and are solutions of the cubic Schroedinger equation for a time-independent potential.

Differential contributions to the interception of occluded ballistic trajectories by the temporoparietal junction, area hMT/V5+, and the intraparietal cortex.

PubMed

Delle Monache, Sergio; Lacquaniti, Francesco; Bosco, Gianfranco

2017-09-01

The ability to catch objects when transiently occluded from view suggests their motion can be extrapolated. Intraparietal cortex (IPS) plays a major role in this process along with other brain structures, depending on the task. For example, interception of objects under Earth's gravity effects may depend on time-to-contact predictions derived from integration of visual signals processed by hMT/V5+ with a priori knowledge of gravity residing in the temporoparietal junction (TPJ). To investigate this issue further, we disrupted TPJ, hMT/V5+, and IPS activities with transcranial magnetic stimulation (TMS) while subjects intercepted computer-simulated projectile trajectories perturbed randomly with either hypo- or hypergravity effects. In experiment 1 , trajectories were occluded either 750 or 1,250 ms before landing. Three subject groups underwent triple-pulse TMS (tpTMS, 3 pulses at 10 Hz) on one target area (TPJ | hMT/V5+ | IPS) and on the vertex (control site), timed at either trajectory perturbation or occlusion. In experiment 2 , trajectories were entirely visible and participants received tpTMS on TPJ and hMT/V5+ with same timing as experiment 1 tpTMS of TPJ, hMT/V5+, and IPS affected differently the interceptive timing. TPJ stimulation affected preferentially responses to 1-g motion, hMT/V5+ all response types, and IPS stimulation induced opposite effects on 0-g and 2-g responses, being ineffective on 1-g responses. Only IPS stimulation was effective when applied after target disappearance, implying this area might elaborate memory representations of occluded target motion. Results are compatible with the idea that IPS, TPJ, and hMT/V5+ contribute to distinct aspects of visual motion extrapolation, perhaps through parallel processing. NEW & NOTEWORTHY Visual extrapolation represents a potential neural solution to afford motor interactions with the environment in the face of missing information. We investigated relative contributions by temporoparietal junction (TPJ), hMT/V5+, and intraparietal cortex (IPS), cortical areas potentially involved in these processes. Parallel organization of visual extrapolation processes emerged with respect to the target's motion causal nature: TPJ was primarily involved for visual motion congruent with gravity effects, IPS for arbitrary visual motion, whereas hMT/V5+ contributed at earlier processing stages. Copyright © 2017 the American Physiological Society.

Probing of multiple magnetic responses in magnetic inductors using atomic force microscopy.

PubMed

Park, Seongjae; Seo, Hosung; Seol, Daehee; Yoon, Young-Hwan; Kim, Mi Yang; Kim, Yunseok

2016-02-08

Even though nanoscale analysis of magnetic properties is of significant interest, probing methods are relatively less developed compared to the significance of the technique, which has multiple potential applications. Here, we demonstrate an approach for probing various magnetic properties associated with eddy current, coil current and magnetic domains in magnetic inductors using multidimensional magnetic force microscopy (MMFM). The MMFM images provide combined magnetic responses from the three different origins, however, each contribution to the MMFM response can be differentiated through analysis based on the bias dependence of the response. In particular, the bias dependent MMFM images show locally different eddy current behavior with values dependent on the type of materials that comprise the MI. This approach for probing magnetic responses can be further extended to the analysis of local physical features.

Time-dependence of the electromechanical bending actuation observed in ionic-electroactive polymers

NASA Astrophysics Data System (ADS)

Bass, Patrick S.; Zhang, Lin; Cheng, Z.-Y.

The characteristics of the electromechanical response observed in an ionic-electroactive polymer (i-EAP) are represented by the time (t) dependence of its bending actuation (y). The electromechanical response of a typical i-EAP — poly(ethylene oxide) (PEO) doped with lithium perchlorate (LP) — is studied. The shortcomings of all existing models describing the electromechanical response obtained in i-EAPs are discussed. A more reasonable model: y=ymaxe-τ/t is introduced to characterize this time dependence for all i-EAPs. The advantages and correctness of this model are confirmed using results obtained in PEO-LP actuators with different LP contents and at different temperatures. The applicability and universality of this model are validated using the reported results obtained from two different i-EAPs: one is Flemion and the other is polypyrrole actuators.

Na and Ca components of action potentials in amphioxus muscle cells

PubMed Central

Hagiwara, S.; Kidokoro, Y.

1971-01-01

1. The ionic mechanism of the action potential produced in lamella-like muscle cells of amphioxus, Branchiostoma californiense, was investigated with intracellular recording and polarization techniques. 2. The resting potential and action potential overshoot in normal saline are -53±5 mV (S.D.) and +29±10 mV (S.D.) respectively. 3. The action potential is eliminated by tetrodotoxin (3 μM) and by replacing NaCl in the saline with Tris-chloride but maintained by replacing Na with Li. 4. After elimination of the normal action potential by tetrodotoxin or replacing Na with Tris, the addition of procaine (7·3 mM) to the external saline makes the membrane capable of producing a regenerative potential change. 5. The peak potential of the regenerative response depends on external Ca concentration in a manner predicted by the Nernst equation with Ca concentrations close to normal. 6. The Ca dependent response is reversibly suppressed by Co or La ions. 7. Similar regenerative responses are obtained when Ca is substituted with Sr or Ba. 8. It is concluded that two independent mechanisms of ionic permeability increase occur in the membrane of amphioxus muscle cell, one to Na and the other to Ca. PMID:5158595

Learning rules for spike timing-dependent plasticity depend on dendritic synapse location.

PubMed

Letzkus, Johannes J; Kampa, Björn M; Stuart, Greg J

2006-10-11

Previous studies focusing on the temporal rules governing changes in synaptic strength during spike timing-dependent synaptic plasticity (STDP) have paid little attention to the fact that synaptic inputs are distributed across complex dendritic trees. During STDP, propagation of action potentials (APs) back to the site of synaptic input is thought to trigger plasticity. However, in pyramidal neurons, backpropagation of single APs is decremental, whereas high-frequency bursts lead to generation of distal dendritic calcium spikes. This raises the question whether STDP learning rules depend on synapse location and firing mode. Here, we investigate this issue at synapses between layer 2/3 and layer 5 pyramidal neurons in somatosensory cortex. We find that low-frequency pairing of single APs at positive times leads to a distance-dependent shift to long-term depression (LTD) at distal inputs. At proximal sites, this LTD could be converted to long-term potentiation (LTP) by dendritic depolarizations suprathreshold for BAC-firing or by high-frequency AP bursts. During AP bursts, we observed a progressive, distance-dependent shift in the timing requirements for induction of LTP and LTD, such that distal synapses display novel timing rules: they potentiate when inputs are activated after burst onset (negative timing) but depress when activated before burst onset (positive timing). These findings could be explained by distance-dependent differences in the underlying dendritic voltage waveforms driving NMDA receptor activation during STDP induction. Our results suggest that synapse location within the dendritic tree is a crucial determinant of STDP, and that synapses undergo plasticity according to local rather than global learning rules.

Coding and Decoding with Adapting Neurons: A Population Approach to the Peri-Stimulus Time Histogram

PubMed Central

Naud, Richard; Gerstner, Wulfram

2012-01-01

The response of a neuron to a time-dependent stimulus, as measured in a Peri-Stimulus-Time-Histogram (PSTH), exhibits an intricate temporal structure that reflects potential temporal coding principles. Here we analyze the encoding and decoding of PSTHs for spiking neurons with arbitrary refractoriness and adaptation. As a modeling framework, we use the spike response model, also known as the generalized linear neuron model. Because of refractoriness, the effect of the most recent spike on the spiking probability a few milliseconds later is very strong. The influence of the last spike needs therefore to be described with high precision, while the rest of the neuronal spiking history merely introduces an average self-inhibition or adaptation that depends on the expected number of past spikes but not on the exact spike timings. Based on these insights, we derive a ‘quasi-renewal equation’ which is shown to yield an excellent description of the firing rate of adapting neurons. We explore the domain of validity of the quasi-renewal equation and compare it with other rate equations for populations of spiking neurons. The problem of decoding the stimulus from the population response (or PSTH) is addressed analogously. We find that for small levels of activity and weak adaptation, a simple accumulator of the past activity is sufficient to decode the original input, but when refractory effects become large decoding becomes a non-linear function of the past activity. The results presented here can be applied to the mean-field analysis of coupled neuron networks, but also to arbitrary point processes with negative self-interaction. PMID:23055914

Poststimulation time interval-dependent effects of motor cortex anodal tDCS on reaction-time task performance.

PubMed

Molero-Chamizo, Andrés; Alameda Bailén, José R; Garrido Béjar, Tamara; García López, Macarena; Jaén Rodríguez, Inmaculada; Gutiérrez Lérida, Carolina; Pérez Panal, Silvia; González Ángel, Gloria; Lemus Corchero, Laura; Ruiz Vega, María J; Nitsche, Michael A; Rivera-Urbina, Guadalupe N

2018-02-01

Anodal transcranial direct current stimulation (tDCS) induces long-term potentiation-like plasticity, which is associated with long-lasting effects on different cognitive, emotional, and motor performances. Specifically, tDCS applied over the motor cortex is considered to improve reaction time in simple and complex tasks. The timing of tDCS relative to task performance could determine the efficacy of tDCS to modulate performance. The aim of this study was to compare the effects of a single session of anodal tDCS (1.5 mA, for 15 min) applied over the left primary motor cortex (M1) versus sham stimulation on performance of a go/no-go simple reaction-time task carried out at three different time points after tDCS-namely, 0, 30, or 60 min after stimulation. Performance zero min after anodal tDCS was improved during the whole course of the task. Performance 30 min after anodal tDCS was improved only in the last block of the reaction-time task. Performance 60 min after anodal tDCS was not significantly different throughout the entire task. These findings suggest that the motor cortex excitability changes induced by tDCS can improve motor responses, and these effects critically depend on the time interval between stimulation and task performance.

Exponential propagators for the Schrödinger equation with a time-dependent potential.

PubMed

Bader, Philipp; Blanes, Sergio; Kopylov, Nikita

2018-06-28

We consider the numerical integration of the Schrödinger equation with a time-dependent Hamiltonian given as the sum of the kinetic energy and a time-dependent potential. Commutator-free (CF) propagators are exponential propagators that have shown to be highly efficient for general time-dependent Hamiltonians. We propose new CF propagators that are tailored for Hamiltonians of the said structure, showing a considerably improved performance. We obtain new fourth- and sixth-order CF propagators as well as a novel sixth-order propagator that incorporates a double commutator that only depends on coordinates, so this term can be considered as cost-free. The algorithms require the computation of the action of exponentials on a vector similar to the well-known exponential midpoint propagator, and this is carried out using the Lanczos method. We illustrate the performance of the new methods on several numerical examples.

Cardiac transient outward potassium current: a pulse chemistry model of frequency-dependent properties.

PubMed

Liu, L; Krinsky, V I; Grant, A O; Starmer, C F

1996-01-01

Recent voltage-clamp studies of isolated myocytes have demonstrated widespread occurrence of a transient outward current (I(to)) carried by potassium ions. In the canine ventricle, this current is well developed in epicardial cells but not in endocardial cells. The resultant spatial dispersion of refractoriness is potentially proarrhythmic and may be amplified by channel blockade. The inactivation and recovery time constants of this channel are in excess of several hundred milliseconds, and consequently channel availability is frequency dependent at physiological stimulation rates. When the time constants associated with transitions between different channel conformations are rapid relative to drug binding kinetics, the interactions between drugs and an ion channel can be approximated by a sequence of first-order reactions, in which binding occurs in pulses in response to pulse train stimulation (pulse chemistry). When channel conformation transition time constants do not meet this constraint, analytical characterizations of the drug-channel interaction must then be modified to reflect the channel time-dependent properties. Here we report that the rate and steady-state amount of frequency-dependent inactivation of I(to) are consistent with a generalization of the channel blockade model: channel availability is reduced in a pulsatile exponential pattern as the stimulation frequency is increased, and the rate of reduction is a linear function of the pulse train depolarizing and recovery intervals. I(to) was reduced in the presence of quinidine. After accounting for the use-dependent availability of I(to) channels, we found little evidence of an additional use-dependent component of block after exposure to quinidine, suggesting that quinidine reacts with both open and closed I(to) channels as though the binding site is continuously accessible. The model provides a useful tool for assessing drug-channel interactions when the reaction cannot be continuously monitored.

Responses and recovery assessment of continuously cultured Nitrosomonas europaea under chronic ZnO nanoparticle stress: Effects of dissolved oxygen.

PubMed

Wu, Junkang; Chang, Yan; Gao, Huan; Liang, Geyu; Yu, Ran; Ding, Zhen

2018-03-01

Although the antibacterial performances of emerging nanoparticles (NPs) have been extensively explored in the nitrifying systems, the impacts of dissolved oxygen (DO) levels on their bio-toxicities to the nitrifiers and the impaired cells' recovery potentials have seldom been addressed yet. In this study, the physiological and transcriptional responses of the typical ammonia oxidizers - Nitrosomonas europaea in a chemostat to the chronic ZnO NP exposure under different DO conditions were investigated. The results indicated that the cells in steady-growth state in the chemostat were more persevering than batch cultured ones to resist ZnO NP stress despite the dose-dependent NP inhibitory effects were observed. In addition, the occurred striking over-expressions of amoA and hao genes at the initial NP exposure stage suggested the cells' self-regulation potentials at the transcriptional level. The low DO (0.5 mg/L) cultured cells displayed higher sensitivity to NP stress than the high DO (2.0 mg/L) cultured ones, probably owning to the inefficient oxygen-dependent electron transfer from ammonia oxidation for energy conversion/production. The following 12-h NP-free batch recovery assays revealed that both high and low DO cultured cells possessed the physiological and metabolic activity recovery potentials, which were in negative correlation with the NP exposure time. The duration of NP stress and the resulting NP dissolution were critical for the cells' damage levels and their performance recoverability. The membrane preservation processes and the associated metabolism regulations were expected to actively participate in the cells' self-adaption to NP stress and thus be responsible for their metabolic activities recovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation.

PubMed

Villacorta, Luis; Minarrieta, Lucia; Salvatore, Sonia R; Khoo, Nicholas K; Rom, Oren; Gao, Zhen; Berman, Rebecca C; Jobbagy, Soma; Li, Lihua; Woodcock, Steven R; Chen, Y Eugene; Freeman, Bruce A; Ferreira, Ana M; Schopfer, Francisco J; Vitturi, Dario A

2018-05-01

Conjugated linoleic acid (CLA) is a prime substrate for intra-gastric nitration giving rise to the formation of nitro-conjugated linoleic acid (NO 2 -CLA). Herein, NO 2 -CLA generation is demonstrated within the context of acute inflammatory responses both in vitro and in vivo. Macrophage activation resulted in dose- and time-dependent CLA nitration and also in the production of secondary electrophilic and non-electrophilic derivatives. Both exogenous NO 2 -CLA as well as that generated in situ, attenuated NF-κB-dependent gene expression, decreased pro-inflammatory cytokine production and up-regulated Nrf2-regulated proteins. Importantly, both CLA nitration and the corresponding downstream anti-inflammatory actions of NO 2 -CLA were recapitulated in a mouse peritonitis model where NO 2 -CLA administration decreased pro-inflammatory cytokines and inhibited leukocyte recruitment. Taken together, our results demonstrate that the formation of NO 2 -CLA has the potential to function as an adaptive response capable of not only modulating inflammation amplitude but also protecting neighboring tissues via the expression of Nrf2-dependent genes. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Escherichia coli cellular responses to exposure to atmospheric-pressure dielectric barrier discharge plasma-treated N-acetylcysteine solution.

PubMed

Ercan, U K; Sen, B; Brooks, A D; Joshi, S G

2018-04-06

To understand the underlying cellular mechanisms during inactivation of Escherichia coli in response to antimicrobial solution of nonthermal plasma-activated N-acetylcysteine (NAC). The recommended techniques were used to demonstrate E. coli cellular and transcriptomic changes caused associated with peroxynitrite and compared with plasma-treated NAC solution. The findings demonstrate that E. coli cells respond to plasma-treated NAC and undergo severe oxidative and nitrosative stress, and leading to stress-induced damages to different components of bacterial cells, which includes loss of membrane potential, formation of oxidized glutathione (GSSG), formation of nitrotyrosine (a known marker of nitrosative stress), DNA damage, and generated a prominent pool of peroxynitrite. Reverse-transcriptase (RT)-polymerase chain reaction analysis of reactive nitrogen species (RNS) responsive genes indicated their differential expressions. For the first time, we report that the plasma-treated NAC solution activates predominantly nitrosative stress-responsive genes in E. coli and is responsible for cell death. The reactive species generated in solutions by nonthermal plasma treatment depends on the type of solution or solvent used. The plasma-treated NAC solution rapidly inactivates E. coli, mostly involving highly RNS generated in NAC solution, and has high potential as disinfectant. © 2018 The Society for Applied Microbiology.

Nonadiabatic Dynamics in Single-Electron Tunneling Devices with Time-Dependent Density-Functional Theory

NASA Astrophysics Data System (ADS)

Dittmann, Niklas; Splettstoesser, Janine; Helbig, Nicole

2018-04-01

We simulate the dynamics of a single-electron source, modeled as a quantum dot with on-site Coulomb interaction and tunnel coupling to an adjacent lead in time-dependent density-functional theory. Based on this system, we develop a time-nonlocal exchange-correlation potential by exploiting analogies with quantum-transport theory. The time nonlocality manifests itself in a dynamical potential step. We explicitly link the time evolution of the dynamical step to physical relaxation timescales of the electron dynamics. Finally, we discuss prospects for simulations of larger mesoscopic systems.

Nonadiabatic Dynamics in Single-Electron Tunneling Devices with Time-Dependent Density-Functional Theory.

PubMed

Dittmann, Niklas; Splettstoesser, Janine; Helbig, Nicole

2018-04-13

We simulate the dynamics of a single-electron source, modeled as a quantum dot with on-site Coulomb interaction and tunnel coupling to an adjacent lead in time-dependent density-functional theory. Based on this system, we develop a time-nonlocal exchange-correlation potential by exploiting analogies with quantum-transport theory. The time nonlocality manifests itself in a dynamical potential step. We explicitly link the time evolution of the dynamical step to physical relaxation timescales of the electron dynamics. Finally, we discuss prospects for simulations of larger mesoscopic systems.

Unified Formulation of the Aeroelasticity of Swept Lifting Surfaces

NASA Technical Reports Server (NTRS)

Silva, Walter; Marzocca, Piergiovanni; Librescu, Liviu

2001-01-01

An unified approach for dealing with stability and aeroelastic response to time-dependent pressure pulses of swept wings in an incompressible flow is developed. To this end the indicial function concept in time and frequency domains, enabling one to derive the proper unsteady aerodynamic loads is used. Results regarding stability in the frequency and time domains, and subcritical aeroelastic response to arbitrary time-dependent external excitation obtained via the direct use of the unsteady aerodynamic derivatives for 3-D wings are supplied. Closed form expressions for unsteady aerodynamic derivatives using this unified approach have been derived and used to illustrate their application to flutter and aeroelastic response to blast and sonic-boom signatures. In this context, an original representation of the aeroelastic response in the phase space was presented and pertinent conclusions on the implications of some basic parameters have been outlined.

Vasoactivity of rucaparib, a PARP-1 inhibitor, is a complex process that involves myosin light chain kinase, P2 receptors, and PARP itself.

PubMed

McCrudden, Cian M; O'Rourke, Martin G; Cherry, Kim E; Yuen, Hiu-Fung; O'Rourke, Declan; Babur, Muhammad; Telfer, Brian A; Thomas, Huw D; Keane, Patrick; Nambirajan, Thiagarajan; Hagan, Chris; O'Sullivan, Joe M; Shaw, Chris; Williams, Kaye J; Curtin, Nicola J; Hirst, David G; Robson, Tracy

2015-01-01

Therapeutic inhibition of poly(ADP-ribose) polymerase (PARP), as monotherapy or to supplement the potencies of other agents, is a promising strategy in cancer treatment. We previously reported that the first PARP inhibitor to enter clinical trial, rucaparib (AG014699), induced vasodilation in vivo in xenografts, potentiating response to temozolomide. We now report that rucaparib inhibits the activity of the muscle contraction mediator myosin light chain kinase (MLCK) 10-fold more potently than its commercially available inhibitor ML-9. Moreover, rucaparib produces additive relaxation above the maximal degree achievable with ML-9, suggesting that MLCK inhibition is not solely responsible for dilation. Inhibition of nitric oxide synthesis using L-NMMA also failed to impact rucaparib's activity. Rucaparib contains the nicotinamide pharmacophore, suggesting it may inhibit other NAD+-dependent processes. NAD+ exerts P2 purinergic receptor-dependent inhibition of smooth muscle contraction. Indiscriminate blockade of the P2 purinergic receptors with suramin abrogated rucaparib-induced vasodilation in rat arterial tissue without affecting ML-9-evoked dilation, although the specific receptor subtypes responsible have not been unequivocally identified. Furthermore, dorsal window chamber and real time tumor vessel perfusion analyses in PARP-1-/- mice indicate a potential role for PARP in dilation of tumor-recruited vessels. Finally, rucaparib provoked relaxation in 70% of patient-derived tumor-associated vessels. These data provide tantalising evidence of the complexity of the mechanism underlying rucaparib-mediated vasodilation.

A new short-term forecasting model for the total electron content storm time disturbances

NASA Astrophysics Data System (ADS)

Tsagouri, Ioanna; Koutroumbas, Konstantinos; Elias, Panagiotis

2018-06-01

This paper aims to introduce a new model for the short-term forecast of the vertical Total Electron Content (vTEC). The basic idea of the proposed model lies on the concept of the Solar Wind driven autoregressive model for Ionospheric short-term Forecast (SWIF). In its original version, the model is operationally implemented in the DIAS system (http://dias.space.noa.gr) and provides alerts and warnings for upcoming ionospheric disturbances, as well as single site and regional forecasts of the foF2 critical frequency over Europe up to 24 h in advance. The forecasts are driven by the real time assessment of the solar wind conditions at ACE location. The comparative analysis of the variations in foF2 and vTEC during eleven geomagnetic storm events that occurred in the present solar cycle 24 reveals similarities but also differences in the storm-time response of the two characteristics with respect to the local time and the latitude of the observation point. Since the aforementioned dependences drive the storm-time forecasts of the SWIF model, the results obtained here support the upgrade of the SWIF's modeling technique in forecasting the storm-time vTEC variation from its onset to full development and recovery. According to the proposed approach, the vTEC storm-time response can be forecasted from 1 to 12-13 h before its onset, depending on the local time of the observation point at storm onset at L1. Preliminary results on the assessment of the performance of the proposed model and further considerations on its potential implementation in operational mode are also discussed.

Regression analysis of sparse asynchronous longitudinal data.

PubMed

Cao, Hongyuan; Zeng, Donglin; Fine, Jason P

2015-09-01

We consider estimation of regression models for sparse asynchronous longitudinal observations, where time-dependent responses and covariates are observed intermittently within subjects. Unlike with synchronous data, where the response and covariates are observed at the same time point, with asynchronous data, the observation times are mismatched. Simple kernel-weighted estimating equations are proposed for generalized linear models with either time invariant or time-dependent coefficients under smoothness assumptions for the covariate processes which are similar to those for synchronous data. For models with either time invariant or time-dependent coefficients, the estimators are consistent and asymptotically normal but converge at slower rates than those achieved with synchronous data. Simulation studies evidence that the methods perform well with realistic sample sizes and may be superior to a naive application of methods for synchronous data based on an ad hoc last value carried forward approach. The practical utility of the methods is illustrated on data from a study on human immunodeficiency virus.

Alternative life histories in the Atlantic salmon: genetic covariances within the sneaker sexual tactic in males.

PubMed

Páez, David James; Bernatchez, Louis; Dodson, Julian J

2011-07-22

Alternative reproductive tactics are ubiquitous in many species. Tactic expression often depends on whether an individual's condition surpasses thresholds that are responsible for activating particular developmental pathways. Two central goals in understanding the evolution of reproductive tactics are quantifying the extent to which thresholds are explained by additive genetic effects, and describing their covariation with condition-related traits. We monitored the development of early sexual maturation that leads to the sneaker reproductive tactic in Atlantic salmon (Salmo salar L.). We found evidence for additive genetic variance in the timing of sexual maturity (which is a measure of the surpassing of threshold values) and body-size traits. This suggests that selection can affect the patterns of sexual development by changing the timing of this event and/or body size. Significant levels of covariation between these traits also occurred, implying a potential for correlated responses to selection. Closer examination of genetic covariances suggests that the detected genetic variation is distributed along at least five directions of phenotypic variation. Our results show that the potential for evolution of the life-history traits constituting this reproductive phenotype is greatly influenced by their patterns of genetic covariance.

Alternative life histories in the Atlantic salmon: genetic covariances within the sneaker sexual tactic in males

PubMed Central

Páez, David James; Bernatchez, Louis; Dodson, Julian J.

2011-01-01

Alternative reproductive tactics are ubiquitous in many species. Tactic expression often depends on whether an individual's condition surpasses thresholds that are responsible for activating particular developmental pathways. Two central goals in understanding the evolution of reproductive tactics are quantifying the extent to which thresholds are explained by additive genetic effects, and describing their covariation with condition-related traits. We monitored the development of early sexual maturation that leads to the sneaker reproductive tactic in Atlantic salmon (Salmo salar L.). We found evidence for additive genetic variance in the timing of sexual maturity (which is a measure of the surpassing of threshold values) and body-size traits. This suggests that selection can affect the patterns of sexual development by changing the timing of this event and/or body size. Significant levels of covariation between these traits also occurred, implying a potential for correlated responses to selection. Closer examination of genetic covariances suggests that the detected genetic variation is distributed along at least five directions of phenotypic variation. Our results show that the potential for evolution of the life-history traits constituting this reproductive phenotype is greatly influenced by their patterns of genetic covariance. PMID:21177685

Evaluation of pre-hospital transport time of stroke patients to thrombolytic treatment.

PubMed

Simonsen, Sofie Amalie; Andresen, Morten; Michelsen, Lene; Viereck, Søren; Lippert, Freddy K; Iversen, Helle Klingenberg

2014-11-13

Effective treatment of stroke is time dependent. Pre-hospital management is an important link in reducing the time from occurrence of stroke symptoms to effective treatment. The aim of this study was to evaluate time used by emergency medical services (EMS) for stroke patients during a five-year period in order to identify potential delays and evaluate the reorganization of EMS in Copenhagen in 2009. We performed a retrospective analysis of ambulance records from stroke patients suitable for thrombolysis from 1 January 2006 to 7 July 2011. We noted response time from dispatch of the ambulance to arrival at the scene, on-scene time and transport time to the hospital-in total, alarm-to-door time. In addition, we noted baseline characteristics. We reviewed 481 records (58% male, median age 66 years). The median (IQR) alarm-to-door time in minutes was 41 (33-52), of which 18 (12-24) minutes were spent on scene. Response time was reduced from the period before to the period after reorganization (7 vs. 5 minutes, p <0.001). In a linear multiple regression model, higher patient age and longer distance to the hospital correlated with significantly longer transportation time (p <0.001). This study shows an unchanged alarm-to-door time of 41 minutes over a five-year period. Response time, but not total alarm-to-door time, was reduced during the five years. On-scene time constituted nearly half of the total alarm-to-door time and is thus a point of focus for improvement.

Real-time characterization of cannabinoid receptor 1 (CB1 ) allosteric modulators reveals novel mechanism of action.

PubMed

Cawston, Erin E; Redmond, William J; Breen, Courtney M; Grimsey, Natasha L; Connor, Mark; Glass, Michelle

2013-10-01

The cannabinoid receptor type 1 (CB1 ) has an allosteric binding site. The drugs ORG27569 {5-chloro-3-ethyl-N-[2-[4-(1-piperidinyl)phenyl]ethyl]-1H-indole-2-carboxamide} and PSNCBAM-1 {1-(4-chlorophenyl)-3-[3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl]urea} have been extensively characterized with regard to their effects on signalling of the orthosteric ligand CP55,940 {(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol}, and studies have suggested that these allosteric modulators increase binding affinity but act as non-competitive antagonists in functional assays. To gain a deeper understanding of allosteric modulation of CB1 , we examined real-time signalling and trafficking responses of the receptor in the presence of allosteric modulators. Studies of CB1 signalling were carried out in HEK 293 and AtT20 cells expressing haemagglutinin-tagged human and rat CB1 . We measured real-time accumulation of cAMP, activation and desensitization of potassium channel-mediated cellular hyperpolarization and CB1 internalization. ORG27569 and PSNCBAM-1 produce a complex, concentration and time-dependent modulation of agonist-mediated regulation of cAMP levels, as well as an increased rate of desensitization of CB1 -mediated cellular hyperpolarization and a decrease in agonist-induced receptor internalization. Contrary to previous studies characterizing allosteric modulators at CB1, this study suggests that the mechanism of action is not non-competitive antagonism of signalling, but rather that enhanced binding results in an increased rate of receptor desensitization and reduced internalization, which results in time-dependent modulation of cAMP signalling. The observed effect of the allosteric modulators is therefore dependent on the time frame over which the signalling response occurs. This finding may have important consequences for the potential therapeutic application of these compounds. © 2013 The British Pharmacological Society.

The effect of mineral reactions and microstructure on long-term experimental fault zone weakening

NASA Astrophysics Data System (ADS)

Niemeijer, Andre R.

2017-04-01

The frictional properties of fault rocks and, in particular, the velocity dependence of friction and associated rate-and-state parameters, are thought to exert an important control on earthquake nucleation and propagation. Experimental results obtained from natural fault gouges typically show that the velocity dependence of friction is a function of both temperature and sliding velocity, indicating that thermally activated time-dependent processes are fundamentally responsible for causing velocity-weakening behavior in silicate-bearing gouges at earthquake "nucleation velocities" (˜ 1 μm/s) and temperatures around 150-300 ˚ C. In addition, slow experiments at velocities of 10s of nm/s using three different fault gouge types all exhibit major weakening with ongoing displacement at constant velocity. Microstructural and microanalytical analyses demonstrate that the development of a weak through-going foliation as well as the (shear-enhanced) formation of new, weak minerals such as talc or muscovite occurred, which both presumably contributed to the observed weakening. Importantly, the slow deformation rates allow for time-dependent viscous deformation (e.g. pressure solution) to occur at low shear stress within the hard, frictionally strong minerals such as quartz. The results highlight the importance of the chemical effects of fluids and microstructural development on long-term fault weakening under slow loading conditions. The resultant frictionally weak fault gouges allow strain to remain localized, yield a strong permeability anisotropy and provide a barrier for rupture propagation. Along-fault variations in the chemical conditions thus have the potential to produce strong contrasts in frictional properties, which can have a large effect on potential earthquake rupture size and style.

The function and molecular identity of inward rectifier channels in vestibular hair cells of the mouse inner ear

PubMed Central

Levin, Michaela E.

2012-01-01

Inner ear hair cells respond to mechanical stimuli with graded receptor potentials. These graded responses are modulated by a host of voltage-dependent currents that flow across the basolateral membrane. Here, we examine the molecular identity and the function of a class of voltage-dependent ion channels that carries the potassium-selective inward rectifier current known as IK1. IK1 has been identified in vestibular hair cells of various species, but its molecular composition and functional contributions remain obscure. We used quantitative RT-PCR to show that the inward rectifier gene, Kir2.1, is highly expressed in mouse utricle between embryonic day 15 and adulthood. We confirmed Kir2.1 protein expression in hair cells by immunolocalization. To examine the molecular composition of IK1, we recorded voltage-dependent currents from type II hair cells in response to 50-ms steps from −124 to −54 in 10-mV increments. Wild-type cells had rapidly activating inward currents with reversal potentials close to the K+ equilibrium potential and a whole-cell conductance of 4.8 ± 1.5 nS (n = 46). In utricle hair cells from Kir2.1-deficient (Kir2.1−/−) mice, IK1 was absent at all stages examined. To identify the functional contribution of Kir2.1, we recorded membrane responses in current-clamp mode. Hair cells from Kir2.1−/− mice had significantly (P < 0.001) more depolarized resting potentials and larger, slower membrane responses than those of wild-type cells. These data suggest that Kir2.1 is required for IK1 in type II utricle hair cells and contributes to hyperpolarized resting potentials and fast, small amplitude receptor potentials in response to current inputs, such as those evoked by hair bundle deflections. PMID:22496522

γ irradiation with different dose rates induces different DNA damage responses in Petunia x hybrida cells.

PubMed

Donà, Mattia; Ventura, Lorenzo; Macovei, Anca; Confalonieri, Massimo; Savio, Monica; Giovannini, Annalisa; Carbonera, Daniela; Balestrazzi, Alma

2013-05-15

In plants, there is evidence that different dose rate exposures to gamma (γ) rays can cause different biological effects. The dynamics of DNA damage accumulation and molecular mechanisms that regulate recovery from radiation injury as a function of dose rate are poorly explored. To highlight dose-rate dependent differences in DNA damage, single cell gel electrophoresis was carried out on regenerating Petunia x hybrida leaf discs exposed to LDR (total dose 50 Gy, delivered at 0.33 Gy min(-1)) and HDR (total doses 50 and 100 Gy, delivered at 5.15 Gy min(-1)) γ-ray in the 0-24h time period after treatments. Significant fluctuations of double strand breaks and different repair capacities were observed between treatments in the 0-4h time period following irradiation. Dose-rate-dependent changes in the expression of the PhMT2 and PhAPX genes encoding a type 2 metallothionein and the cytosolic isoform of ascorbate peroxidase, respectively, were detected by Quantitative RealTime-Polymerase Chain Reaction. The PhMT2 and PhAPX genes were significantly up-regulated (3.0- and 0.7-fold) in response to HDR. The results are discussed in light of the potential practical applications of LDR-based treatments in mutation breeding. Copyright © 2013 Elsevier GmbH. All rights reserved.

Integrating Clarus data in traffic signal system operation : a survivable real-time weather-responsive system.

DOT National Transportation Integrated Search

2011-07-11

This report presents a prototype of a secure, dependable, real-time weather-responsive traffic signal system. The prototype executes two tasks: 1) accesses weather information that provides near real-time atmospheric and pavement surface condition ob...

Coupled matter-wave solitons in optical lattices

NASA Astrophysics Data System (ADS)

Golam Ali, Sk; Talukdar, B.

2009-06-01

We make use of a potential model to study the dynamics of two coupled matter-wave or Bose-Einstein condensate (BEC) solitons loaded in optical lattices. With separate attention to linear and nonlinear lattices we find some remarkable differences for response of the system to effects of these lattices. As opposed to the case of linear optical lattice (LOL), the nonlinear lattice (NOL) can be used to control the mutual interaction between the two solitons. For a given lattice wave number k, the effective potentials in which the two solitons move are such that the well (Veff(NOL)), resulting from the juxtaposition of soliton interaction and nonlinear lattice potential, is deeper than the corresponding well Veff(LOL). But these effective potentials have opposite k dependence in the sense that the depth of Veff(LOL) increases as k increases and that of Veff(NOL) decreases for higher k values. We verify that the effectiveness of optical lattices to regulate the motion of the coupled solitons depends sensitively on the initial locations of the motionless solitons as well as values of the lattice wave number. For both LOL and NOL the two solitons meet each other due to mutual interaction if their initial locations are taken within the potential wells with the difference that the solitons in the NOL approach each other rather rapidly and take roughly half the time to meet as compared with the time needed for such coalescence in the LOL. In the NOL, the soliton profiles can move freely and respond to the lattice periodicity when the separation between their initial locations are as twice as that needed for a similar free movement in the LOL. We observe that, in both cases, slow tuning of the optical lattices by varying k with respect to a time parameter τ drags the oscillatory solitons apart to take them to different locations. In our potential model the oscillatory solitons appear to propagate undistorted. But a fully numerical calculation indicates that during evolution they exhibit decay and revival.

Source analysis of short and long latency vestibular-evoked potentials (VsEPs) produced by left vs. right ear air-conducted 500 Hz tone pips.

PubMed

Todd, N P M; Paillard, A C; Kluk, K; Whittle, E; Colebatch, J G

2014-06-01

Todd et al. (2014) have recently demonstrated the presence of vestibular dependent changes both in the morphology and in the intensity dependence of auditory evoked potentials (AEPs) when passing through the vestibular threshold as determined by vestibular evoked myogenic potentials (VEMPs). In this paper we extend this work by comparing left vs. right ear stimulation and by conducting a source analysis of the resulting evoked potentials of short and long latency. Ten healthy, right-handed subjects were recruited and evoked potentials were recorded to both left- and right-ear sound stimulation, above and below vestibular threshold. Below VEMP threshold, typical AEPs were recorded, consisting of mid-latency (MLR) waves Na and Pa followed by long latency AEPs (LAEPs) N1 and P2. In the supra-threshold condition, the expected changes in morphology were observed, consisting of: (1) short-latency vestibular evoked potentials (VsEPs) which have no auditory correlate, i.e. the ocular VEMP (OVEMP) and inion response related potentials; (2) a later deflection, labelled N42/P52, followed by the LAEPs N1 and P2. Statistical analysis of the vestibular dependent responses indicated a contralateral effect for inion related short-latency responses and a left-ear/right-hemisphere advantage for the long-latency responses. Source analysis indicated that the short-latency effects may be mediated by a contralateral projection to left cerebellum, while the long-latency effects were mediated by a contralateral projection to right cingulate cortex. In addition we found evidence of a possible vestibular contribution to the auditory T-complex in radial temporal lobe sources. These last results raise the possibility that acoustic activation of the otolith organs could potentially contribute to auditory processing. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Prediction of visual evoked potentials at any surface location from a set of three recording electrodes.

PubMed

Mazinani, Babac A E; Waberski, Till D; van Ooyen, Andre; Walter, Peter

2008-05-01

Purpose of this study was to introduce a mathematical model which allows the calculation of a source dipole as the origin of the evoked activity based on the data of three simultaneously recorded VEPs from different locations at the scalp surface to predict field potentials at any neighboring location and to validate this model by comparison with actual recordings. In 10 healthy subjects (25-38, mean 29 years) continuous VEPs were recorded via 96 channels. On the base of the recordings at the positions POz', O1' and O2', a source dipole vector was calculated for each time point of the recordings and VEP responses were back projected for any of the 96 electrode positions. Differences between the calculated and the actually recorded responses were quantified by coefficients of variation (CV). The prediction precision and response size depended on the distance between the electrode of the predicted response and the recording electrodes. After compensating this relationship using a polynomial function, the CV of the mean difference between calculated and recorded responses of the 10 subjects was 2.8 +/- 1.2%. In conclusion, the "Mini-Brainmapping" model can provide precise topographical information with minimal additional recording efforts with good reliability. The implementation of this method in a routine diagnostic setting as an "easy-to-do" procedure would allow to examine a large number of patients and normal subjects in a short time, and thus, a solid data base could be created to correlate well defined pathologies with topographical VEP changes.

Vestibular evoked myogenic potentials in response to lateral skull taps are dependent on two different mechanisms.

PubMed

Brantberg, Krister; Westin, Magnus; Löfqvist, Lennart; Verrecchia, Luca; Tribukait, Arne

2009-05-01

To explore the mechanisms for skull tap induced vestibular evoked myogenic potentials (VEMP). The muscular responses were recorded over both sternocleidomastoid (SCM) muscles using skin electrodes. A skull tapper which provided a constant stimulus intensity was used to test cervical vestibular evoked myogenic potentials (VEMP) in response to lateral skull taps in healthy subjects (n=10) and in patients with severe unilateral loss of vestibular function (n=10). Skull taps applied approximately 2 cm above the outer ear canal caused highly reproducible VEMP. There were differences in VEMP in both normals and patients depending on side of tapping. In normals, there was a positive-negative ("normal") VEMP on the side contra-lateral to the skull tapping, but no significant VEMP ipsi-laterally. In patients, skull taps above the lesioned ear caused a contra-lateral positive-negative VEMP (as it did in the normals), in addition there was an ipsi-lateral negative-positive ("inverted") VEMP. When skull taps were presented above the healthy ear there was only a small contra-lateral positive-negative VEMP but, similar to the normals, no VEMP ipsi-laterally. The present data, in conjunction with earlier findings, support a theory that skull-tap VEMP responses are mediated by two different mechanisms. It is suggested that skull tapping causes both a purely ipsi-lateral stimulus side independent SCM response and a bilateral and of opposite polarity SCM response that is stimulus side dependent. Possibly, the skull tap induced VEMP responses are the sum of a stimulation of two species of vestibular receptors, one excited by vibration (which is rather stimulus site independent) and one excited by translation (which is more stimulus site dependent). Skull-tap VEMP probably have two different mechanisms. Separation of the two components might reveal the status of different labyrinthine functions.

A Conditional Joint Modeling Approach for Locally Dependent Item Responses and Response Times

ERIC Educational Resources Information Center

Meng, Xiang-Bin; Tao, Jian; Chang, Hua-Hua

2015-01-01

The assumption of conditional independence between the responses and the response times (RTs) for a given person is common in RT modeling. However, when the speed of a test taker is not constant, this assumption will be violated. In this article we propose a conditional joint model for item responses and RTs, which incorporates a covariance…

Central and peripheral components of short latency vestibular responses in the chicken

NASA Technical Reports Server (NTRS)

Nazareth, A. M.; Jones, T. A.

1998-01-01

Far-field recordings of short latency vestibular responses to pulsed cranial translation are composed of a series of positive and negative peaks occurring within 10 ms following stimulus onset. In the bird, these vestibular evoked potentials (VsEPs) can be recorded noninvasively and have been shown in the chicken and quail to depend strictly upon the activation of the vestibular component of the eighth nerve. The utility of the VsEP in the study of vestibular systems is dependent upon a clear understanding of the neural sources of response components. The primary aim of the current research in the chicken was to critically test the hypotheses that 1) responses are generated by both peripheral and central neurons and 2) peaks P1 and N1 originate from first order vestibular neurons, whereas later waves primarily depend on activity in higher order neurons. The principal strategy used here was to surgically isolate the eighth nerve as it enters the brainstem. Interruption of primary afferents of the eighth nerve in the brainstem substantially reduced or eliminated peaks beyond P2, whereas P1 and N1 were generally spared. Surgical sections that spared vestibular pathways had little effect on responses. The degree of change in response components beyond N1 was correlated with the extent of damage to central vestibular relays. These findings support the conclusion that responses are produced by both peripheral and central elements of the vestibular system. Further, response peaks later than N1 appear to be dependent upon central relays, whereas P1 and N1 reflect activity of the peripheral nerve. These findings clarify the roles of peripheral and central neurons in the generation of vestibular evoked potentials and provide the basis for a more useful and detailed interpretation of data from vestibular response testing.

Mental fatigue and impaired response processes: event-related brain potentials in a Go/NoGo task.

PubMed

Kato, Yuichiro; Endo, Hiroshi; Kizuka, Tomohiro

2009-05-01

The effects of mental fatigue on the availability of cognitive resources and associated response-related processes were examined using event-related brain potentials. Subjects performed a Go/NoGo task for 60 min. Reaction time, number of errors, and mental fatigue scores all significantly increased with time spent on the task. The NoGo-P3 amplitude significantly decreased with time on task, but the Go-P3 amplitude was not modulated. The amplitude of error-related negativity (Ne/ERN) also decreased with time on task. These results indicate that mental fatigue attenuates resource allocation and error monitoring for NoGo stimuli. The Go- and NoGo-P3 latencies both increased with time on task, indicative of a delay in stimulus evaluation time due to mental fatigue. NoGo-N2 latency increased with time on task, but NoGo-N2 amplitude was not modulated. The amplitude of response-locked lateralized readiness potential (LRP) significantly decreased with time on task. Mental fatigue appears to slows down the time course of response inhibition, and impairs the intensity of response execution.

Investigation of endothelial function by pulse contour analysis: a protocol for drug administration and timing of pulse contour assessment

PubMed Central

Gordon, Sarah E; Cartwright, Neil; Griffiths, Mark J D

2009-01-01

AIMS Pulse contour analysis (PCA) obtained by finger photoplethysmography produces a digital volume pulse (DVP) including an inflection point in its down-slope. The reflection index (RI: ratio of the inflection point height over the maximal DVP) is responsive to vasodilatation. We aimed to optimize the drug dose and time interval for assessing endothelial function using PCA in healthy volunteers and patients with severe coronary artery disease. METHODS Time and dose to RI response relationships were constructed in 16 volunteers and nine patients to inhaled salbutamol (100–400 µg) or sublingual nitroglycerin (NTG; 25–400 µg). RESULTS For the volunteers, the time to maximum RI response to inhaled salbutamol and sublingual NTG was 10.73 ± 0.41 and 3.66 ± 0.21 min, respectively. A plateau in the RI response to salbutamol occurred between 5 and 15 min after inhalation and results were averaged over this period. A dose-dependent response was observed to inhaled salbutamol and sublingual NTG (P= 0.05 and P < 0.001 by repeated-measures anova, respectively) in healthy volunteers. By contrast, in patients with severe coronary artery disease inhaled salbutamol (100–400 µg) did not cause a significant change in RI. CONCLUSIONS In healthy volunteers the RI response to inhaled salbutamol (100–200 µg) averaged over 5–15 min after administration may be used to investigate endothelial function by PCA. The response to sublingual NTG (50 µg) should be determined at 4 min. This technique may not be suitable for the assessment of endothelial function in subjects with extensive coronary artery disease owing to the small responses observed and potential confounding effect of vasoactive medication. PMID:19843066

Possible evidence for re-regulation of HPA axis and brain reward systems over time in treatment in prescription opioid-dependent patients.

PubMed

Bunce, Scott C; Harris, Jonathan D; Bixler, Edward O; Taylor, Megan; Muelly, Emilie; Deneke, Erin; Thompson, Kenneth W; Meyer, Roger E

2015-01-01

There is growing evidence for a neuroadaptive model underlying vulnerability to relapse in opioid dependence. The purpose of this study was to evaluate clinical measures hypothesized to mirror elements of allostatic dysregulation in patients dependent on prescription opioids at 2 time points after withdrawal, compared with healthy control participants. Recently withdrawn (n = 7) prescription opioid-dependent patients were compared with the patients in supervised residential care for 2 to 3 months (extended care; n = 7) and healthy controls (n = 7) using drug cue reactivity, affect-modulated startle response tasks, salivary cortisol, and 8 days of sleep actigraphy. Prefrontal cortex was monitored with functional near-infrared spectroscopy during the cue reactivity task. Startle response results indicated reduced hedonic response to natural rewards among patients recently withdrawn from opioids relative to extended care patients. The recently withdrawn patients showed increased activation to pill stimuli in right dorsolateral prefrontal cortex relative to extended care patients. Cortisol levels were elevated among recently withdrawn patients and intermediate for extended care relative to healthy controls. Actigraphy indicated disturbed sleep between recently withdrawn patients and extended care patients; extended care patients were similar to controls. Dorsolateral prefrontal cortex activation to drug and natural reward cues, startle responses to natural reward cues, day-time cortisol levels, time in bed, and total time spent sleeping were all correlated with the number of days since last drug use (ie, time in supervised residential treatment). These results suggest possible re-regulation of dysregulated hypothalamic-pituitary-adrenal axis and brain reward systems in prescription opioid-dependent patients over the drug-free period in residential treatment.

Evoked-potential recovery during double click stimulation in a whale: a possibility of biosonar automatic gain control.

PubMed

Supin, Alexander Ya; Nachtigall, Paul E; Breese, Marlee

2007-01-01

False killer whale Pseudorca crassidens auditory brainstem responses (ABR) were recorded using a double-click stimulation paradigm specifically measuring the recovery of the second response (to the test click) as a function of the inter-click interval (ICI) at various levels of the conditioning and test click. At all click intensities, the slopes of recovery functions were almost constant: 0.6-0.8 microV per ICI decade. Therefore, even when the conditioning-to-test-click level ratio was kept constant, the duration of recovery was intensity-dependent: The higher intensity the longer the recovery. The conditioning-to-test-click level ratio strongly influenced the recovery time: The higher the ratio, the longer the recovery. The dependence was almost linear using a logarithmic ICI scale with a rate of 25-30 dB per ICI decade. These data were used for modeling the interaction between the emitted click and the echo during echolocation, assuming that the two clicks simulated the transmitted and echo clicks. This simulation showed that partial masking of the echo by the preceding emitted click may explain the independence of echo-response amplitude of target distance. However, the distance range where this mechanism is effective depends on the emitted click level: The higher the level, the greater the range. @ 2007 Acoustical Society of America.

Continuous-wave infrared optical nerve stimulation for potential diagnostic applications

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Cilip, Christopher M.; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2010-09-01

Optical nerve stimulation using infrared laser radiation has recently been developed as a potential alternative to electrical nerve stimulation. However, recent studies have focused primarily on pulsed delivery of the laser radiation and at relatively low pulse rates. The objective of this study is to demonstrate faster optical stimulation of the prostate cavernous nerves using continuous-wave (cw) infrared laser radiation for potential diagnostic applications. A thulium fiber laser (λ=1870 nm) is used for noncontact optical stimulation of the rat prostate cavernous nerves in vivo. Optical nerve stimulation, as measured by an intracavernous pressure (ICP) response in the penis, is achieved with the laser operating in either cw mode, or with a 5-ms pulse duration at 10, 20, 30, 40, 50, and 100 Hz. Successful optical stimulation is observed to be primarily dependent on a threshold nerve temperature (42 to 45 °C), rather than an incident fluence, as previously reported. cw optical nerve stimulation provides a significantly faster ICP response time using a lower power (and also less expensive) laser than pulsed stimulation. cw optical nerve stimulation may therefore represent an alternative mode of stimulation for intraoperative diagnostic applications where a rapid response is critical, such as identification of the cavernous nerves during prostate cancer surgery.

Universal time-dependent dispersion properties for diffusion in a one-dimensional critically tilted potential

NASA Astrophysics Data System (ADS)

Guérin, T.; Dean, D. S.

2017-01-01

We consider the time-dependent dispersion properties of overdamped tracer particles diffusing in a one-dimensional periodic potential under the influence of an additional constant tilting force F . The system is studied in the region where the force is close to the critical value Fc at which the barriers separating neighboring potential wells disappear. We show that, when F crosses the critical value, the shape of the mean-square displacement (MSD) curves is strongly modified. We identify a diffusive regime at intermediate-time scales with an effective diffusion coefficient which is much larger than the late-time diffusion coefficient for F >Fc , whereas for F

Time-Driven Effects on Processing Relative Clauses

ERIC Educational Resources Information Center

Schremm, Andrea; Horne, Merle; Roll, Mikael

2016-01-01

The present response time study investigated how a hypothesized time-based working memory constraint of 2-3 s affects the resolution of grammatical and semantic dependencies. Congruent and incongruent object relative (OR) and subject relative sentences were read at different presentation rates so that the distance between dependent words was…

Thermodynamic responses of electronic systems.

PubMed

Franco-Pérez, Marco; Ayers, Paul W; Gázquez, José L; Vela, Alberto

2017-09-07

We present how the framework of the temperature-dependent chemical reactivity theory can describe the panorama of different types of interactions between an electronic system and external reagents. The key reactivity indicators are responses of an appropriate state function (like the energy or grand potential) to the variables that determine the state of the system (like the number of electrons/chemical potential, external potential, and temperature). We also consider the response of the average electron density to appropriate perturbations. We present computable formulas for these reactivity indicators and discuss their chemical utility for describing electronic, electrostatic, and thermal changes associated with chemical processes.

Thermodynamic responses of electronic systems

NASA Astrophysics Data System (ADS)

Franco-Pérez, Marco; Ayers, Paul W.; Gázquez, José L.; Vela, Alberto

2017-09-01

We present how the framework of the temperature-dependent chemical reactivity theory can describe the panorama of different types of interactions between an electronic system and external reagents. The key reactivity indicators are responses of an appropriate state function (like the energy or grand potential) to the variables that determine the state of the system (like the number of electrons/chemical potential, external potential, and temperature). We also consider the response of the average electron density to appropriate perturbations. We present computable formulas for these reactivity indicators and discuss their chemical utility for describing electronic, electrostatic, and thermal changes associated with chemical processes.

Indentation mapping revealed poroelastic, but not viscoelastic, properties spanning native zonal articular cartilage.

PubMed

Wahlquist, Joseph A; DelRio, Frank W; Randolph, Mark A; Aziz, Aaron H; Heveran, Chelsea M; Bryant, Stephanie J; Neu, Corey P; Ferguson, Virginia L

2017-12-01

Osteoarthrosis is a debilitating disease affecting millions, yet engineering materials for cartilage regeneration has proven difficult because of the complex microstructure of this tissue. Articular cartilage, like many biological tissues, produces a time-dependent response to mechanical load that is critical to cell's physiological function in part due to solid and fluid phase interactions and property variations across multiple length scales. Recreating the time-dependent strain and fluid flow may be critical for successfully engineering replacement tissues but thus far has largely been neglected. Here, microindentation is used to accomplish three objectives: (1) quantify a material's time-dependent mechanical response, (2) map material properties at a cellular relevant length scale throughout zonal articular cartilage and (3) elucidate the underlying viscoelastic, poroelastic, and nonlinear poroelastic causes of deformation in articular cartilage. Untreated and trypsin-treated cartilage was sectioned perpendicular to the articular surface and indentation was used to evaluate properties throughout zonal cartilage on the cut surface. The experimental results demonstrated that within all cartilage zones, the mechanical response was well represented by a model assuming nonlinear biphasic behavior and did not follow conventional viscoelastic or linear poroelastic models. Additionally, 10% (w/w) agarose was tested and, as anticipated, behaved as a linear poroelastic material. The approach outlined here provides a method, applicable to many tissues and biomaterials, which reveals and quantifies the underlying causes of time-dependent deformation, elucidates key aspects of material structure and function, and that can be used to provide important inputs for computational models and targets for tissue engineering. Elucidating the time-dependent mechanical behavior of cartilage, and other biological materials, is critical to adequately recapitulate native mechanosensory cues for cells. We used microindentation to map the time-dependent properties of untreated and trypsin treated cartilage throughout each cartilage zone. Unlike conventional approaches that combine viscoelastic and poroelastic behaviors into a single framework, we deconvoluted the mechanical response into separate contributions to time-dependent behavior. Poroelastic effects in all cartilage zones dominated the time-dependent behavior of articular cartilage, and a model that incorporates tension-compression nonlinearity best represented cartilage mechanical behavior. These results can be used to assess the success of regeneration and repair approaches, as design targets for tissue engineering, and for development of accurate computational models. Copyright © 2017 Acta Materialia Inc. All rights reserved.

Modeling the time-varying and level-dependent effects of the medial olivocochlear reflex in auditory nerve responses.

PubMed

Smalt, Christopher J; Heinz, Michael G; Strickland, Elizabeth A

2014-04-01

The medial olivocochlear reflex (MOCR) has been hypothesized to provide benefit for listening in noisy environments. This advantage can be attributed to a feedback mechanism that suppresses auditory nerve (AN) firing in continuous background noise, resulting in increased sensitivity to a tone or speech. MOC neurons synapse on outer hair cells (OHCs), and their activity effectively reduces cochlear gain. The computational model developed in this study implements the time-varying, characteristic frequency (CF) and level-dependent effects of the MOCR within the framework of a well-established model for normal and hearing-impaired AN responses. A second-order linear system was used to model the time-course of the MOCR using physiological data in humans. The stimulus-level-dependent parameters of the efferent pathway were estimated by fitting AN sensitivity derived from responses in decerebrate cats using a tone-in-noise paradigm. The resulting model uses a binaural, time-varying, CF-dependent, level-dependent OHC gain reduction for both ipsilateral and contralateral stimuli that improves detection of a tone in noise, similarly to recorded AN responses. The MOCR may be important for speech recognition in continuous background noise as well as for protection from acoustic trauma. Further study of this model and its efferent feedback loop may improve our understanding of the effects of sensorineural hearing loss in noisy situations, a condition in which hearing aids currently struggle to restore normal speech perception.

Combined effect of storm movement and drainage network configuration on flood peaks

NASA Astrophysics Data System (ADS)

Seo, Yongwon; Son, Kwang Ik; Choi, Hyun Il

2016-04-01

This presentation reports the combined effect of storm movement and drainage network layout on resulting hydrographs and its implication to flood process and also flood mitigation. First, we investigate, in general terms, the effects of storm movement on the resulting flood peaks, and the underlying process controls. For this purpose, we utilize a broad theoretical framework that uses characteristic time and space scales associated with stationary rainstorms as well as moving rainstorms. For a stationary rainstorm the characteristic timescales that govern the peak response include two intrinsic timescales of a catchment and one extrinsic timescale of a rainstorm. On the other hand, for a moving rainstorm, two additional extrinsic scales are required; the storm travel time and storm size. We show that the relationship between the peak response and the timescales appropriate for a stationary rainstorm can be extended in a straightforward manner to describe the peak response for a moving rainstorm. For moving rainstorms, we show that the augmentation of peak response arises from both effect of overlaying the responses from subcatchments (resonance condition) and effect of increased responses from subcatchments due to increased duration (interdependence), which results in maximum peak response when the moving rainstorm is slower than the channel flow velocity. Second, we show the relation between channel network configurations and hydrograph sensitivity to storm kinematics. For this purpose, Gibbs' model is used to evaluate the network characteristics. The results show that the storm kinematics that produces the maximum peak discharge depends on the network configuration because the resonance condition changes with the network configuration. We show that an "efficient" network layout is more sensitive and results in higher increase in peak response compared to "inefficient" one. These results imply different flood potential risks for river networks depending on network characteristics. In addition, they imply a possibility of an alternative drainage network layout as an effective measure for flood mitigation in urban environments.

Hydrocortisone-induced anti-inflammatory effects in immature human enterocytes depend on the timing of exposure.

PubMed

Rautava, Samuli; Walker, W Allan; Lu, Lei

2016-06-01

The immature human gut has a propensity to exaggerated inflammatory responses that are thought to play a role in the pathogenesis of necrotizing enterocolitis (NEC). Prenatal exposure to corticosteroids has been reported to reduce the risk of NEC, while postnatal dexamethasone treatment is associated with adverse neurodevelopmental outcomes in preterm infants. The aim of this study was to investigate the direct role of hydrocortisone in gene expression patterns and inflammatory responses in immature human enterocytes. Time-dependent hydrocortisone effects in nontransformed primary human fetal intestinal epithelial cell line H4 were investigated by cDNA microarray. Fetal intestinal organ culture and cell culture experiments were conducted. Inflammatory responses were induced by stimulation with IL-1β and TNF-α with and without hydrocortisone. IL-8 and IL-6 expression and secretion were measured as functional readout. Here we report time-dependent hydrocortisone-induced changes in gene expression patterns detected by cDNA microarray. Hydrocortisone significantly attenuated IL-1β-induced inflammatory responses in the immature human gut when administered at the time of the proinflammatory insult: IL-1β-induced IL-8 and IL-6 secretion in the fetal ileum as well as H4 cells were significantly reduced. Hydrocortisone also inhibited IL-8 secretion in response to TNF-α. In contrast, TNF-α-induced IL-8 secretion was not reduced in cells treated with hydrocortisone for 48 h before stimulation. Our observations provide a physiological basis for understanding the differential clinical effects of corticosteroids in the immature human gut depending on the timing of treatment. Copyright © 2016 the American Physiological Society.

Hydrocortisone-induced anti-inflammatory effects in immature human enterocytes depend on the timing of exposure

PubMed Central

Rautava, Samuli; Lu, Lei

2016-01-01

The immature human gut has a propensity to exaggerated inflammatory responses that are thought to play a role in the pathogenesis of necrotizing enterocolitis (NEC). Prenatal exposure to corticosteroids has been reported to reduce the risk of NEC, while postnatal dexamethasone treatment is associated with adverse neurodevelopmental outcomes in preterm infants. The aim of this study was to investigate the direct role of hydrocortisone in gene expression patterns and inflammatory responses in immature human enterocytes. Time-dependent hydrocortisone effects in nontransformed primary human fetal intestinal epithelial cell line H4 were investigated by cDNA microarray. Fetal intestinal organ culture and cell culture experiments were conducted. Inflammatory responses were induced by stimulation with IL-1β and TNF-α with and without hydrocortisone. IL-8 and IL-6 expression and secretion were measured as functional readout. Here we report time-dependent hydrocortisone-induced changes in gene expression patterns detected by cDNA microarray. Hydrocortisone significantly attenuated IL-1β-induced inflammatory responses in the immature human gut when administered at the time of the proinflammatory insult: IL-1β-induced IL-8 and IL-6 secretion in the fetal ileum as well as H4 cells were significantly reduced. Hydrocortisone also inhibited IL-8 secretion in response to TNF-α. In contrast, TNF-α-induced IL-8 secretion was not reduced in cells treated with hydrocortisone for 48 h before stimulation. Our observations provide a physiological basis for understanding the differential clinical effects of corticosteroids in the immature human gut depending on the timing of treatment. PMID:27056727

Hierarchical effects of pro-inflammatory cytokines on the post-influenza susceptibility to pneumococcal coinfection

NASA Astrophysics Data System (ADS)

Duvigneau, Stefanie; Sharma-Chawla, Niharika; Boianelli, Alessandro; Stegemann-Koniszewski, Sabine; Nguyen, Van Kinh; Bruder, Dunja; Hernandez-Vargas, Esteban A.

2016-11-01

In the course of influenza A virus (IAV) infections, a secondary bacterial infection frequently leads to serious respiratory conditions provoking high hospitalization and death tolls. Although abundant pro-inflammatory responses have been reported as key contributing factors for these severe dual infections, the relative contributions of cytokines remain largely unclear. In the current study, mathematical modelling based on murine experimental data dissects IFN-γ as a cytokine candidate responsible for impaired bacterial clearance, thereby promoting bacterial growth and systemic dissemination during acute IAV infection. We also found a time-dependent detrimental role of IL-6 in curtailing bacterial outgrowth which was not as distinct as for IFN-γ. Our numerical simulations suggested a detrimental effect of IFN-γ alone and in synergism with IL-6 but no conclusive pathogenic effect of IL-6 and TNF-α alone. This work provides a rationale to understand the potential impact of how to manipulate temporal immune components, facilitating the formulation of hypotheses about potential therapeutic strategies to treat coinfections.

A preliminary empirical evaluation of virtual reality as an instructional medium for visual-spatial tasks

NASA Technical Reports Server (NTRS)

Regian, J. Wesley; Shebilske, Wayne; Monk, John M.

1993-01-01

We explored the training potential of Virtual Reality (VR) technology. Thirty-one adults were trained and tested on spatial skills in a VR. They learned a sequence of button and knob responses on a VR console and performed flawlessly on the same console. Half were trained with a rote strategy; the rest used a meaningful strategy. Response times were equivalent for both groups and decreased significantly over five test trials indicating that learning continued on VR tests. The same subjects practiced navigating through a VR building, which had three floors with four rooms on each floor. The dependent measure was the number of rooms traversed on routes that differed from training routes. Many subjects completed tests in the fewest rooms possible. All subjects learned configurational knowledge according to the criterion of taking paths that were significantly shorter than those predicted by a random walk as determined by a Monte Carlo analysis. The results were discussed as a departure point for empirically testing the training potential of VR technology.

Fuel Cell Backup Power System for Grid Service and Micro-Grid in Telecommunication Applications: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Zhiwen; Eichman, Joshua D; Kurtz, Jennifer M

This paper presents the feasibility and economics of using fuel cell backup power systems in telecommunication cell towers to provide grid services (e.g., ancillary services, demand response). The fuel cells are able to provide power for the cell tower during emergency conditions. This study evaluates the strategic integration of clean, efficient, and reliable fuel cell systems with the grid for improved economic benefits. The backup systems have potential as enhanced capability through information exchanges with the power grid to add value as grid services that depend on location and time. The economic analysis has been focused on the potential revenuemore » for distributed telecommunications fuel cell backup units to provide value-added power supply. This paper shows case studies on current fuel cell backup power locations and regional grid service programs. The grid service benefits and system configurations for different operation modes provide opportunities for expanding backup fuel cell applications responsive to grid needs.« less

Short- and medium-term plasticity associated with augmenting responses in cortical slabs and spindles in intact cortex of cats in vivo

PubMed Central

Timofeev, Igor; Grenier, François; Bazhenov, Maxim; Houweling, Arthur R; Sejnowski, Terrence J; Steriade, Mircea

2002-01-01

Plastic changes in the synaptic responsiveness of neocortical neurones, which occur after rhythmic stimuli within the frequency range of sleep spindles (10 Hz), were investigated in isolated neocortical slabs and intact cortex of anaesthetized cats by means of single, dual and triple simultaneous intracellular recordings in conjunction with recordings of local field potential responses. In isolated cortical slabs (10 mm long, 6 mm wide and 4–5 mm deep), augmenting responses to pulse-trains at 10 Hz (responses with growing amplitudes from the second stimulus in a train) were elicited only by relatively high-intensity stimuli. At low intensities, responses were decremental. The largest augmenting responses were evoked in neurones located close to the stimulation site. Quantitative analyses of the number of action potentials and the amplitude and area of depolarization during augmenting responses in a population of neurones recorded from slabs showed that the most dramatic increases in the number of spikes with successive stimuli, and the greatest increase in depolarization amplitude, were found in conventional fast-spiking (FS) neurones. The largest increase in the area of depolarization was found in regular-spiking (RS) neurones. Dual intracellular recordings from a pair of FS and RS neurones in the slab revealed more action potentials in the FS neurone during augmenting responses and a significant increase in the depolarization area of the RS neurone that was dependent on the firing of the FS neurone. Self-sustained seizures could occur in the slab after rhythmic stimuli at 10 Hz. In the intact cortex, repeated sequences of stimuli generating augmenting responses or spontaneous spindles could induce an increased synaptic responsiveness to single stimuli, which lasted for several minutes. A similar time course of increased responsiveness was obtained with induction of cellular plasticity. These data suggest that augmenting responses elicited by stimulation, as well as spontaneously occurring spindles, may induce short- and medium-term plasticity of neuronal responses. PMID:12122155

Short and prolonged exposure to hyperglycaemia in human fibroblasts and endothelial cells: metabolic and osmotic effects.

PubMed

Moruzzi, Noah; Del Sole, Marianna; Fato, Romana; Gerdes, Jantje M; Berggren, Per-Olof; Bergamini, Christian; Brismar, Kerstin

2014-08-01

High blood glucose levels are the main feature of diabetes. However, the underlying mechanism linking high glucose concentration to diabetic complications is still not fully elucidated, particularly with regard to human physiology. Excess of glucose is likely to trigger a metabolic response depending on the cell features, activating deleterious pathways involved in the complications of diabetes. In this study, we aim to elucidate how acute and prolonged hyperglycaemia alters the biology and metabolism in human fibroblasts and endothelial cells. We found that hyperglycaemia triggers a metabolic switch from oxidative phosphorylation to glycolysis that is maintained over prolonged time. Moreover, osmotic pressure is a major factor in the early metabolic response, decreasing both mitochondrial transmembrane potential and cellular proliferation. After prolonged exposure to hyperglycaemia we observed decreased mitochondrial steady-state and uncoupled respiration, together with a reduced ATP/ADP ratio. At the same time, we could not detect major changes in mitochondrial transmembrane potential and reactive oxygen species. We suggest that the physiological and metabolic alterations observed in healthy human primary fibroblasts and endothelial cells are an adaptive response to hyperglycaemia. The severity of metabolic and bioenergetics impairment associated with diabetic complications may occur after longer glucose exposure or due to interactions with cell types more sensitive to hyperglycaemia. Copyright © 2014 Elsevier Ltd. All rights reserved.

A method for decoding the neurophysiological spike-response transform.

PubMed

Stern, Estee; García-Crescioni, Keyla; Miller, Mark W; Peskin, Charles S; Brezina, Vladimir

2009-11-15

Many physiological responses elicited by neuronal spikes-intracellular calcium transients, synaptic potentials, muscle contractions-are built up of discrete, elementary responses to each spike. However, the spikes occur in trains of arbitrary temporal complexity, and each elementary response not only sums with previous ones, but can itself be modified by the previous history of the activity. A basic goal in system identification is to characterize the spike-response transform in terms of a small number of functions-the elementary response kernel and additional kernels or functions that describe the dependence on previous history-that will predict the response to any arbitrary spike train. Here we do this by developing further and generalizing the "synaptic decoding" approach of Sen et al. (1996). Given the spike times in a train and the observed overall response, we use least-squares minimization to construct the best estimated response and at the same time best estimates of the elementary response kernel and the other functions that characterize the spike-response transform. We avoid the need for any specific initial assumptions about these functions by using techniques of mathematical analysis and linear algebra that allow us to solve simultaneously for all of the numerical function values treated as independent parameters. The functions are such that they may be interpreted mechanistically. We examine the performance of the method as applied to synthetic data. We then use the method to decode real synaptic and muscle contraction transforms.

A method for decoding the neurophysiological spike-response transform

PubMed Central

Stern, Estee; García-Crescioni, Keyla; Miller, Mark W.; Peskin, Charles S.; Brezina, Vladimir

2009-01-01

Many physiological responses elicited by neuronal spikes—intracellular calcium transients, synaptic potentials, muscle contractions—are built up of discrete, elementary responses to each spike. However, the spikes occur in trains of arbitrary temporal complexity, and each elementary response not only sums with previous ones, but can itself be modified by the previous history of the activity. A basic goal in system identification is to characterize the spike-response transform in terms of a small number of functions—the elementary response kernel and additional kernels or functions that describe the dependence on previous history—that will predict the response to any arbitrary spike train. Here we do this by developing further and generalizing the “synaptic decoding” approach of Sen et al. (J Neurosci 16:6307-6318, 1996). Given the spike times in a train and the observed overall response, we use least-squares minimization to construct the best estimated response and at the same time best estimates of the elementary response kernel and the other functions that characterize the spike-response transform. We avoid the need for any specific initial assumptions about these functions by using techniques of mathematical analysis and linear algebra that allow us to solve simultaneously for all of the numerical function values treated as independent parameters. The functions are such that they may be interpreted mechanistically. We examine the performance of the method as applied to synthetic data. We then use the method to decode real synaptic and muscle contraction transforms. PMID:19695289

The impact of intratracheally instilled carbon black on the cardiovascular system of rats: elevation of blood homocysteine and hyperactivity of platelets.

PubMed

Kim, Hwa; Oh, Seok-Jeong; Kwak, Hui-Chan; Kim, Jong-Kyu; Lim, Cheol-Hong; Yang, Jeong-Sun; Park, Kwangsik; Kim, Sang-Kyum; Lee, Moo-Yeol

2012-01-01

Carbon black (CB) is an industrial chemical with high potential for human exposure. Although the relationship between exposure to particulate matter (PM) and cardiovascular disease is well documented, the risk of adverse cardiovascular effects attributed to CB particles has not been clearly characterized. This study was performed to (1) investigate the effects of CB on cardiovascular system and (2) identify the target tissue or potential biomarkers. Carbon black with a distinct particle size, N330 (ultrafine particle) and N990 (fine particle), was intratracheally instilled into rats at a doses of 1, 3, or 10 mg/kg. Measurements of thrombotic activity and determination of plasma homocysteine levels, cardiac functionality, and inflammatory responses were conducted at 24-h and 1-wk time points. Exposure to N330 accelerated platelet-dependent blood clotting at 10 mg/kg, the highest exposure tested. Unexpectedly, both N330 and N990 led to prolongation of activated partial thromboplastin time (aPTT), whereas these CB particles failed to affect prothrombin time (PT). N990 produced a significant elevation in the level of plasma homocysteine, a well-established etiological factor in cardiovascular diseases. Both N330 and N990 induced apparent inflammation in the lungs; however, both particles failed to initiate systemic inflammation. Neither CB particle produced observable cardiac symptoms as detected by electrocardiography. Taken together, data show CB exposure enhanced the cardiovascular risk by inducing hyperhomocysteinemia and platelet hyperactivity, although these effects may be variable depending on particle size and exposure duration. Homocysteine may be a potential biomarker for cardiovascular toxicity following CB exposure.

Time-dependent density-functional theory with optimized effective potential and self-interaction correction and derivative discontinuity for the treatment of double ionization of He and Be atoms in intense laser fields

NASA Astrophysics Data System (ADS)

Heslar, John; Telnov, Dmitry A.; Chu, Shih-I.

2013-05-01

We present a self-interaction-free time-dependent density-functional theory (TDDFT) for the treatment of double-ionization processes of many-electron systems. The method is based on the extension of the Krieger-Li-Iafrate (KLI) treatment of the optimized effective potential (OEP) theory and the incorporation of an explicit self-interaction correction (SIC) term. In the framework of the time-dependent density functional theory, we have performed three-dimensional (3D) calculations of double ionization of He and Be atoms by intense near-infrared laser fields. We make use of the exchange-correlation potential with the integer discontinuity which improves the description of the double-ionization process. We found that a proper description of the double ionization requires the TDDFT exchange-correlation potential with the discontinuity with respect to the variation of the total particle number (TPN). The results for the intensity-dependent rates of double ionization of He and Be atoms are presented.

Dose- and Time-Dependent Transcriptional Response of Ishikawa Cells Exposed to Genistein

PubMed Central

Naciff, Jorge M.; Khambatta, Zubin S.; Carr, Gregory J.; Tiesman, Jay P.; Singleton, David W.; Khan, Sohaib A.; Daston, George P.

2016-01-01

To further define the utility of the Ishikawa cells as a reliable in vitro model to determine the potential estrogenic activity of chemicals of interest, transcriptional changes induced by genistein (GES) in Ishikawa cells at various doses (10 pM, 1 nM, 100 nM, and 10 μM) and time points (8, 24, and 48 h) were identified using a comprehensive microarray approach. Trend analysis indicated that the expression of 5342 unique genes was modified by GES in a dose- and time-dependent manner (P ≤ 0.0001). However, the majority of gene expression changes induced in Ishikawa cells were elicited by the highest dose of GES evaluated (10 μM). The GES’ estrogenic activity was identified by comparing the Ishikawa cells’ response to GES versus 17 α-ethynyl estradiol (EE, at equipotent doses, ie, 10 μM vs 1 μM, respectively) and was defined by changes in the expression of 284 unique genes elicited by GES and EE in the same direction, although the magnitude of the change for some genes was different. Further, comparing the response of the Ishikawa cells exposed to high doses of GES and EE versus the response of the juvenile rat uterus exposed to EE, we identified 66 unique genes which were up- or down regulated in a similar manner in vivo as well as in vitro. Genistein elicits changes in multiple molecular pathways affecting various biological processes particularly associated with cell organization and biogenesis, regulation of translation, cell proliferation, and intracellular transport; processes also affected by estrogen exposure in the uterus of the rat. These results indicate that Ishikawa cells are capable of generating a biologically relevant estrogenic response and offer an in vitro model to assess this mode of action. PMID:26865667

Dose- and Time-Dependent Transcriptional Response of Ishikawa Cells Exposed to Genistein.

PubMed

Naciff, Jorge M; Khambatta, Zubin S; Carr, Gregory J; Tiesman, Jay P; Singleton, David W; Khan, Sohaib A; Daston, George P

2016-05-01

To further define the utility of the Ishikawa cells as a reliable in vitro model to determine the potential estrogenic activity of chemicals of interest, transcriptional changes induced by genistein (GES) in Ishikawa cells at various doses (10 pM, 1 nM, 100 nM, and 10 μM) and time points (8, 24, and 48 h) were identified using a comprehensive microarray approach. Trend analysis indicated that the expression of 5342 unique genes was modified by GES in a dose- and time-dependent manner (P ≤ 0.0001). However, the majority of gene expression changes induced in Ishikawa cells were elicited by the highest dose of GES evaluated (10 μM). The GES' estrogenic activity was identified by comparing the Ishikawa cells' response to GES versus 17 α-ethynyl estradiol (EE, at equipotent doses, ie, 10 μM vs 1 μM, respectively) and was defined by changes in the expression of 284 unique genes elicited by GES and EE in the same direction, although the magnitude of the change for some genes was different. Further, comparing the response of the Ishikawa cells exposed to high doses of GES and EE versus the response of the juvenile rat uterus exposed to EE, we identified 66 unique genes which were up- or down regulated in a similar manner in vivo as well as in vitro Genistein elicits changes in multiple molecular pathways affecting various biological processes particularly associated with cell organization and biogenesis, regulation of translation, cell proliferation, and intracellular transport; processes also affected by estrogen exposure in the uterus of the rat. These results indicate that Ishikawa cells are capable of generating a biologically relevant estrogenic response and offer an in vitro model to assess this mode of action. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Human Milk Oligosaccharides Attenuate Antigen-Antibody Complex Induced Chemokine Release from Human Intestinal Epithelial Cell Lines.

PubMed

Zehra, Sehrish; Khambati, Ibrahim; Vierhout, Megan; Mian, M Firoz; Buck, Rachael; Forsythe, Paul

2018-02-01

There has been increased interest in the use of dietary ingredients, including prebiotics such as human-milk oligosaccharides (HMOs), as therapeutic strategies for food allergy. Understanding the mechanisms underlying the beneficial effects of HMOs is important to realizing their therapeutic potential. Here we demonstrate that the HMO, 6'-sialyllactose (6'SL) inhibited chemokine (IL-8 and CCL20) release from T-84 and HT-29 cells stimulated with antigen-antibody complex, TNFα or PGE 2 ; an effect that was PPARγ dependent and associated with decreased activity of the transcription factors AP-1 and NFκB. In contrast, 2'-fucosyllactose (2'FL) selectively inhibited CCL20 release in response to antigen antibody complex in a PPARγ independent manner. This study reinforces the concept that structurally different oligosaccharides have distinct biological activities and identifies, for the first time, that the HMOs, 6'SL, and 2'FL, modulate human epithelial cell responses related to allergic disease. These findings encourage further investigation of the therapeutic potential of specific HMOs in food allergy. This study provides evidence for direct effects of HMOs in addition to their prebiotic role and demonstrates, for the first time, modulation of Ag-IgE complex activation of human epithelial cells that may have important implications for food-allergy. The study also reinforces the concept that structurally different oligosaccharides have distinct biological activities. In determining the composition of infant formula, addition of oligosaccharides with specific structures may provide direct modulation of immune responses and potentially attenuate symptoms or development of food allergy. © 2018 Institute of Food Technologists®.

Mechanisms of Dexamethasone-Mediated Inhibition of Toll-Like Receptor Signaling Induced by Neisseria meningitidis and Streptococcus pneumoniae▿

PubMed Central

Mogensen, Trine H.; Berg, Randi S.; Paludan, Søren R.; Østergaard, Lars

2008-01-01

Excessive inflammation contributes to the pathogenesis of bacterial meningitis, which remains a serious disease despite treatment with antibiotics. Therefore, anti-inflammatory drugs have important therapeutic potential, and clinical trials have revealed that early treatment with dexamethasone significantly reduces mortality and morbidity from bacterial meningitis. Here we investigate the molecular mechanisms behind the inhibitory effect of dexamethasone upon the inflammatory responses evoked by Neisseria meningitidis and Streptococcus pneumoniae, two of the major causes of bacterial meningitis. The inflammatory cytokine response was dependent on Toll-like receptor signaling and was strongly inhibited by dexamethasone. Activation of the NF-κB pathway was targeted at several levels, including inhibition of IκB phosphorylation and NF-κB DNA-binding activity as well as upregulation of IκBα synthesis. Our data also revealed that the timing of steroid treatment relative to infection was important for achieving strong inhibition, particularly in response to S. pneumoniae. Altogether, we describe important targets of dexamethasone in the inflammatory responses evoked by N. meningitidis and S. pneumoniae, which may contribute to our understanding of the clinical effect and the importance of timing with respect to corticosteroid treatment during bacterial meningitis. PMID:17938219

Expression of proliferative and inflammatory markers in a full-thickness human skin equivalent following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

PubMed Central

Black, Adrienne T.; Hayden, Patrick J.; Casillas, Robert P.; Heck, Diane E.; Gerecke, Donald R.; Sinko, Patrick J.; Laskin, Debra L.; Laskin, Jeffrey D.

2010-01-01

Sulfur mustard is a potent vesicant that induces inflammation, edema and blistering following dermal exposure. To assess molecular mechanisms mediating these responses, we analyzed the effects of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide, on EpiDerm-FT™, a commercially available full-thickness human skin equivalent. CEES (100–1000 μM) caused a concentration-dependent increase in pyknotic nuclei and vacuolization in basal keratinocytes; at high concentrations (300–1000 μM), CEES also disrupted keratin filament architecture in the stratum corneum. This was associated with time-dependent increases in expression of proliferating cell nuclear antigen, a marker of cell proliferation, and poly(ADP-ribose) polymerase (PARP) and phosphorylated histone H2AX, markers of DNA damage. Concentration- and time-dependent increases in mRNA and protein expression of eicosanoid biosynthetic enzymes including COX-2, 5-lipoxygenase, microsomal PGE2 synthases, leukotriene (LT) A4 hydrolase and LTC4 synthase were observed in CEES-treated skin equivalents, as well as in antioxidant enzymes, glutathione S-transferases A1–2 (GSTA1–2), GSTA3 and GSTA4. These data demonstrate that CEES induces rapid cellular damage, cytotoxicity and inflammation in full-thickness skin equivalents. These effects are similar to human responses to vesicants in vivo and suggest that the full thickness skin equivalent is a useful in vitro model to characterize the biological effects of mustards and to develop potential therapeutics. PMID:20840853

Climate Sensitivity, Sea Level, and Atmospheric Carbon Dioxide

NASA Technical Reports Server (NTRS)

Hansen, James; Sato, Makiko; Russell, Gary; Kharecha, Pushker

2013-01-01

Cenozoic temperature, sea level and CO2 covariations provide insights into climate sensitivity to external forcings and sea-level sensitivity to climate change. Climate sensitivity depends on the initial climate state, but potentially can be accurately inferred from precise palaeoclimate data. Pleistocene climate oscillations yield a fast-feedback climate sensitivity of 3+/-1deg C for a 4 W/sq m CO2 forcing if Holocene warming relative to the Last Glacial Maximum (LGM) is used as calibration, but the error (uncertainty) is substantial and partly subjective because of poorly defined LGM global temperature and possible human influences in the Holocene. Glacial-to-interglacial climate change leading to the prior (Eemian) interglacial is less ambiguous and implies a sensitivity in the upper part of the above range, i.e. 3-4deg C for a 4 W/sq m CO2 forcing. Slow feedbacks, especially change of ice sheet size and atmospheric CO2, amplify the total Earth system sensitivity by an amount that depends on the time scale considered. Ice sheet response time is poorly defined, but we show that the slow response and hysteresis in prevailing ice sheet models are exaggerated. We use a global model, simplified to essential processes, to investigate state dependence of climate sensitivity, finding an increased sensitivity towards warmer climates, as low cloud cover is diminished and increased water vapour elevates the tropopause. Burning all fossil fuels, we conclude, would make most of the planet uninhabitable by humans, thus calling into question strategies that emphasize adaptation to climate change.

Expression of proliferative and inflammatory markers in a full-thickness human skin equivalent following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide.

PubMed

Black, Adrienne T; Hayden, Patrick J; Casillas, Robert P; Heck, Diane E; Gerecke, Donald R; Sinko, Patrick J; Laskin, Debra L; Laskin, Jeffrey D

2010-12-01

Sulfur mustard is a potent vesicant that induces inflammation, edema and blistering following dermal exposure. To assess molecular mechanisms mediating these responses, we analyzed the effects of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide, on EpiDerm-FT™, a commercially available full-thickness human skin equivalent. CEES (100-1000 μM) caused a concentration-dependent increase in pyknotic nuclei and vacuolization in basal keratinocytes; at high concentrations (300-1000 μM), CEES also disrupted keratin filament architecture in the stratum corneum. This was associated with time-dependent increases in expression of proliferating cell nuclear antigen, a marker of cell proliferation, and poly(ADP-ribose) polymerase (PARP) and phosphorylated histone H2AX, markers of DNA damage. Concentration- and time-dependent increases in mRNA and protein expression of eicosanoid biosynthetic enzymes including COX-2, 5-lipoxygenase, microsomal PGE₂ synthases, leukotriene (LT) A₄ hydrolase and LTC₄ synthase were observed in CEES-treated skin equivalents, as well as in antioxidant enzymes, glutathione S-transferases A1-2 (GSTA1-2), GSTA3 and GSTA4. These data demonstrate that CEES induces rapid cellular damage, cytotoxicity and inflammation in full-thickness skin equivalents. These effects are similar to human responses to vesicants in vivo and suggest that the full thickness skin equivalent is a useful in vitro model to characterize the biological effects of mustards and to develop potential therapeutics. Copyright © 2010 Elsevier Inc. All rights reserved.

Independent predictors of reliability between full time employee-dependent acquisition of functional outcomes compared to non-full time employee-dependent methodologies: a prospective single institutional study.

PubMed

Adogwa, Owoicho; Elsamadicy, Aladine A; Cheng, Joseph; Bagley, Carlos

2016-03-01

The prospective acquisition of reliable patient-reported outcomes (PROs) measures demonstrating the effectiveness of spine surgery, or lack thereof, remains a challenge. The aims of this study are to compare the reliability of functional outcomes metrics obtained using full time employee (FTE) vs. non-FTE-dependent methodologies and to determine the independent predictors of response reliability using non FTE-dependent methodologies. One hundred and nineteen adult patients (male: 65, female: 54) undergoing one- and two-level lumbar fusions at Duke University Medical Center were enrolled in this prospective study. Enrollment criteria included available demographic, clinical and baseline functional outcomes data. All patients were administered two similar sets of baseline questionnaires-(I) phone interviews (FTE-dependent) and (II) hardcopy in clinic (patient self-survey, non-FTE-dependent). All patients had at least a two-week washout period between phone interviews and in-clinic self-surveys to minimize effect of recall. Questionnaires included Oswestry disability index (ODI) and Visual Analog Back and Leg Pain Scale (VAS-BP/LP). Reliability was assessed by the degree to which patient responses to baseline questionnaires differed between both time points. About 26.89% had a history an anxiety disorder and 28.57% reported a history of depression. At least 97.47% of patients had a High School Diploma or GED, with 49.57% attaining a 4-year college degree or post-graduate degree. 29.94% reported full-time employment and 14.28% were on disability. There was a very high correlation between baseline PRO's data captured between FTE-dependent compared to non-FTE-dependent methodologies (r=0.89). In a multivariate logistic regression model, the absence of anxiety and depression, higher levels of education (college or greater) and full-time employment, were independently associated with high response reliability using non-FTE-dependent methodologies. Our study suggests that capturing health-related quality of life data using non-FTE-dependent methodologies is highly reliable and maybe a more cost-effective alternative. Well-educated patients who are employed full-time appear to be the most reliable.

Impulse-response functions and anthropogenic CO2

NASA Technical Reports Server (NTRS)

Tubiello, Francesco N.; Oppenheimer, Michael

1995-01-01

Non-linearities in the carbon cycle make the response to atmospheric CO2 perturbations dependent on emission history. We show that even when linear representations of the carbon cycle are used, the calculation of time scales characterizing the removal of excess CO2 depends on past emissions.

GABAB receptor-mediated, layer-specific synaptic plasticity reorganizes gamma-frequency neocortical response to stimulation

PubMed Central

Ainsworth, Matthew; Lee, Shane; Kaiser, Marcus; Simonotto, Jennifer; Kopell, Nancy J.

2016-01-01

Repeated presentations of sensory stimuli generate transient gamma-frequency (30–80 Hz) responses in neocortex that show plasticity in a task-dependent manner. Complex relationships between individual neuronal outputs and the mean, local field potential (population activity) accompany these changes, but little is known about the underlying mechanisms responsible. Here we show that transient stimulation of input layer 4 sufficient to generate gamma oscillations induced two different, lamina-specific plastic processes that correlated with lamina-specific changes in responses to further, repeated stimulation: Unit rates and recruitment showed overall enhancement in supragranular layers and suppression in infragranular layers associated with excitatory or inhibitory synaptic potentiation onto principal cells, respectively. Both synaptic processes were critically dependent on activation of GABAB receptors and, together, appeared to temporally segregate the cortical representation. These data suggest that adaptation to repetitive sensory input dramatically alters the spatiotemporal properties of the neocortical response in a manner that may both refine and minimize cortical output simultaneously. PMID:27118845

GABAB receptor-mediated, layer-specific synaptic plasticity reorganizes gamma-frequency neocortical response to stimulation.

PubMed

Ainsworth, Matthew; Lee, Shane; Kaiser, Marcus; Simonotto, Jennifer; Kopell, Nancy J; Whittington, Miles A

2016-05-10

Repeated presentations of sensory stimuli generate transient gamma-frequency (30-80 Hz) responses in neocortex that show plasticity in a task-dependent manner. Complex relationships between individual neuronal outputs and the mean, local field potential (population activity) accompany these changes, but little is known about the underlying mechanisms responsible. Here we show that transient stimulation of input layer 4 sufficient to generate gamma oscillations induced two different, lamina-specific plastic processes that correlated with lamina-specific changes in responses to further, repeated stimulation: Unit rates and recruitment showed overall enhancement in supragranular layers and suppression in infragranular layers associated with excitatory or inhibitory synaptic potentiation onto principal cells, respectively. Both synaptic processes were critically dependent on activation of GABAB receptors and, together, appeared to temporally segregate the cortical representation. These data suggest that adaptation to repetitive sensory input dramatically alters the spatiotemporal properties of the neocortical response in a manner that may both refine and minimize cortical output simultaneously.

Subgap time of flight: A spectroscopic study of deep levels in semi-insulating CdTe:Cl

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pousset, J.; Farella, I.; Cola, A., E-mail: adriano.cola@le.imm.cnr.it

2016-03-14

We report on a study of deep levels in semi-insulating CdTe:Cl by means of a time-of-flight spectral approach. By varying the wavelength of a pulsed optical source within the CdTe energy gap, transitions to/from localized levels generate free carriers which are analysed through the induced photocurrent transients. Both acceptor-like centers, related to the A-center, and a midgap level, 0.725 eV from the valence band, have been detected. The midgap level is close to the Fermi level and is possibly a recombination center responsible for the compensation mechanism. When the irradiance is varied, either linear or quadratic dependence of the electron andmore » hole collected charge are observed, depending on the dominant optical transitions. The analysis discloses the potentiality of such a novel approach exploitable in the field of photorefractive materials as well as for deep levels spectroscopy.« less

A nonlinear dynamical analogue model of geomagnetic activity

NASA Technical Reports Server (NTRS)

Klimas, A. J.; Baker, D. N.; Roberts, D. A.; Fairfield, D. H.; Buechner, J.

1992-01-01

Consideration is given to the solar wind-magnetosphere interaction within the framework of deterministic nonlinear dynamics. An earlier dripping faucet analog model of the low-dimensional solar wind-magnetosphere system is reviewed, and a plasma physical counterpart to that model is constructed. A Faraday loop in the magnetotail is considered, and the relationship of electric potentials on the loop to changes in the magnetic flux threading the loop is developed. This approach leads to a model of geomagnetic activity which is similar to the earlier mechanical model but described in terms of the geometry and plasma contents of the magnetotail. The model is characterized as an elementary time-dependent global convection model. The convection evolves within a magnetotail shape that varies in a prescribed manner in response to the dynamical evolution of the convection. The result is a nonlinear model capable of exhibiting a transition from regular to chaotic loading and unloading. The model's behavior under steady loading and also some elementary forms of time-dependent loading is discussed.

Calcium responses to synaptically activated bursts of action potentials and their synapse-independent replay in cultured networks of hippocampal neurons.

PubMed

Bengtson, C Peter; Kaiser, Martin; Obermayer, Joshua; Bading, Hilmar

2013-07-01

Both synaptic N-methyl-d-aspartate (NMDA) receptors and voltage-operated calcium channels (VOCCs) have been shown to be critical for nuclear calcium signals associated with transcriptional responses to bursts of synaptic input. However the direct contribution to nuclear calcium signals from calcium influx through NMDA receptors and VOCCs has been obscured by their concurrent roles in action potential generation and synaptic transmission. Here we compare calcium responses to synaptically induced bursts of action potentials with identical bursts devoid of any synaptic contribution generated using the pre-recorded burst as the voltage clamp command input to replay the burst in the presence of blockers of action potentials or ionotropic glutamate receptors. Synapse independent replays of bursts produced nuclear calcium responses with amplitudes around 70% of their original synaptically generated signals and were abolished by the L-type VOCC blocker, verapamil. These results identify a major direct source of nuclear calcium from local L-type VOCCs whose activation is boosted by NMDA receptor dependent depolarization. The residual component of synaptically induced nuclear calcium signals which was both VOCC independent and NMDA receptor dependent showed delayed kinetics consistent with a more distal source such as synaptic NMDA receptors or internal stores. The dual requirement of NMDA receptors and L-type VOCCs for synaptic activity-induced nuclear calcium dependent transcriptional responses most likely reflects a direct somatic calcium influx from VOCCs whose activation is amplified by synaptic NMDA receptor-mediated depolarization and whose calcium signal is boosted by a delayed input from distal calcium sources mostly likely entry through NMDA receptors and release from internal stores. This article is part of a Special Issue entitled: 12th European Symposium on Calcium. Copyright © 2013 Elsevier B.V. All rights reserved.

High-Frequency Response of the Atmospheric Electric Potential Gradient Under Strong and Dry Boundary-Layer Convection

NASA Astrophysics Data System (ADS)

Conceição, Ricardo; Silva, Hugo Gonçalves; Bennett, Alec; Salgado, Rui; Bortoli, Daniele; Costa, Maria João; Collares Pereira, Manuel

2018-01-01

The spectral response of atmospheric electric potential gradient gives important information about phenomena affecting this gradient at characteristic time scales ranging from years (e.g., solar modulation) to fractions of a second (e.g., turbulence). While long-term time scales have been exhaustively explored, short-term scales have received less attention. At such frequencies, space-charge transport inside the planetary boundary layer becomes a sizeable contribution to the potential gradient variability. For the first time, co-located (Évora, Portugal) measurements of boundary-layer backscatter profiles and the 100-Hz potential gradient are reported. Five campaign days are analyzed, providing evidence for a relation between high-frequency response of the potential gradient and strong dry convection.

Nonreciprocal quantum Hall devices with driven edge magnetoplasmons in two-dimensional materials

NASA Astrophysics Data System (ADS)

Bosco, S.; DiVincenzo, D. P.

2017-05-01

We develop a theory that describes the response of nonreciprocal devices employing two-dimensional materials in the quantum Hall regime capacitively coupled to external electrodes. As the conduction in these devices is understood to be associated to the edge magnetoplasmons (EMPs), we first investigate the EMP problem by using the linear response theory in the random phase approximation. Our model can incorporate several cases that were often treated on different grounds in literature. In particular, we analyze plasmonic excitations supported by a smooth and sharp confining potential in a two-dimensional electron gas, and in monolayer graphene, and we point out the similarities and differences in these materials. We also account for a general time-dependent external drive applied to the system. Finally, we describe the behavior of a nonreciprocal quantum Hall device: the response contains additional resonant features, which were not foreseen from previous models.

Inducing repetitive action potential firing in neurons via synthesized photoresponsive nanoscale cellular prostheses.

PubMed

Lu, Siyuan; Madhukar, Anupam

2013-02-01

Recently we reported an analysis that examined the potential of synthesized photovoltaic functional abiotic nanosystems (PVFANs) to modulate membrane potential and activate action potential firing in neurons. Here we extend the analysis to delineate the requirements on the electronic energy levels and the attendant photophysical properties of the PVFANs to induce repetitive action potential under continuous light, a capability essential for the proposed potential application of PVFANs as retinal cellular prostheses to compensate for loss of photoreceptors. We find that repetitive action potential firing demands two basic characteristics in the electronic response of the PVFANs: an exponential dependence of the PVFAN excited state decay rate on the membrane potential and a three-state system such that, following photon absorption, the electron decay from the excited state to the ground state is via intermediate state(s) whose lifetime is comparable to the refractory time following an action potential. In this study, the potential of synthetic photovoltaic functional abiotic nanosystems (PVFANs) is examined under continuous light to modulate membrane potential and activate action potential firing in neurons with the proposed potential application of PVFANs as retinal cellular prostheses. Copyright © 2013 Elsevier Inc. All rights reserved.

Short-duration stimulation of the supplementary eye fields perturbs anti-saccade performance while potentiating contralateral head orienting.

PubMed

Chapman, Brendan B; Corneil, Brian D

2014-01-01

Many forms of brain stimulation utilize the notion of state dependency, whereby greater influences are observed when a given area is more engaged at the time of stimulation. Here, by delivering intracortical microstimulation (ICMS) to the supplementary eye fields (SEF) of monkeys performing interleaved pro- and anti-saccades, we show a surprising diversity of state-dependent effects of ICMS-SEF. Short-duration ICMS-SEF passed around cue presentation selectively disrupted anti-saccades by increasing reaction times and error rates bilaterally, and also recruited neck muscles, favoring contralateral head turning to a greater degree on anti-saccade trials. These results are consistent with the functional relevance of the SEF for anti-saccades. The multiplicity of stimulation-evoked effects, with ICMS-SEF simultaneously disrupting anti-saccade performance and facilitating contralateral head orienting, probably reflects both the diversity of cortical and subcortical targets of SEF projections, and the response of this oculomotor network to stimulation. We speculate that the bilateral disruption of anti-saccades arises via feedback loops that may include the thalamus, whereas neck muscle recruitment arises via feedforward polysynaptic pathways to the motor periphery. Consideration of both sets of results reveals a more complete picture of the highly complex and multiphasic response to ICMS-SEF that can play out differently in different effector systems.

A robust sound perception model suitable for neuromorphic implementation.

PubMed

Coath, Martin; Sheik, Sadique; Chicca, Elisabetta; Indiveri, Giacomo; Denham, Susan L; Wennekers, Thomas

2013-01-01

We have recently demonstrated the emergence of dynamic feature sensitivity through exposure to formative stimuli in a real-time neuromorphic system implementing a hybrid analog/digital network of spiking neurons. This network, inspired by models of auditory processing in mammals, includes several mutually connected layers with distance-dependent transmission delays and learning in the form of spike timing dependent plasticity, which effects stimulus-driven changes in the network connectivity. Here we present results that demonstrate that the network is robust to a range of variations in the stimulus pattern, such as are found in naturalistic stimuli and neural responses. This robustness is a property critical to the development of realistic, electronic neuromorphic systems. We analyze the variability of the response of the network to "noisy" stimuli which allows us to characterize the acuity in information-theoretic terms. This provides an objective basis for the quantitative comparison of networks, their connectivity patterns, and learning strategies, which can inform future design decisions. We also show, using stimuli derived from speech samples, that the principles are robust to other challenges, such as variable presentation rate, that would have to be met by systems deployed in the real world. Finally we demonstrate the potential applicability of the approach to real sounds.

Inflammatory Pain Reduces C Fiber Activity-Dependent Slowing in a Sex-Dependent Manner, Amplifying Nociceptive Input to the Spinal Cord

PubMed Central

McCormick, Barry; Lukito, Veny; Wilson, Kirsten L.

2017-01-01

C fibers display activity-dependent slowing (ADS), whereby repetitive stimulation (≥1 Hz) results in a progressive slowing of action potential conduction velocity, which manifests as a progressive increase in response latency. However, the impact of ADS on spinal pain processing has not been explored, nor whether ADS is altered in inflammatory pain conditions. To investigate, compound action potentials were made, from dorsal roots isolated from rats with or without complete Freund's adjuvant (CFA) hindpaw inflammation, in response to electrical stimulus trains. CFA inflammation significantly reduced C fiber ADS at 1 and 2 Hz stimulation rates. Whole-cell patch-clamp recordings in the spinal cord slice preparation with attached dorsal roots also demonstrated that CFA inflammation reduced ADS in the monosynaptic C fiber input to lamina I neurokinin 1 receptor-expressing neurons (1–10 Hz stimulus trains) without altering the incidence of synaptic response failures. When analyzed by sex, it was revealed that females display a more pronounced ADS that is reduced by CFA inflammation to a level comparable with males. Cumulative ventral root potentials evoked by long and short dorsal root stimulation lengths, to maximize and minimize the impact of ADS, respectively, demonstrated that reducing ADS facilitates spinal summation, and this was also sex dependent. This finding correlated with the behavioral observation of increased noxious thermal thresholds and enhanced inflammatory thermal hypersensitivity in females. We propose that sex/inflammation-dependent regulation of C fiber ADS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dependent differences in pain sensitivity. SIGNIFICANCE STATEMENT The intensity of a noxious stimulus is encoded by the frequency of action potentials relayed by nociceptive C fibers to the spinal cord. C fibers conduct successive action potentials at progressively slower speeds, but the impact of this activity-dependent slowing (ADS) is unknown. Here we demonstrate that ADS is more prevalent in females than males and is reduced in an inflammatory pain model in females only. We also demonstrate a progressive delay of C fiber monosynaptic transmission to the spinal cord that is similarly sex and inflammation dependent. Experimentally manipulating ADS strongly influences spinal summation consistent with sex differences in behavioral pain thresholds. This suggests that ADS provides a peripheral mechanism that can regulate spinal nociceptive processing and pain sensation. PMID:28576935

The effect of stimulus strength on the speed and accuracy of a perceptual decision.

PubMed

Palmer, John; Huk, Alexander C; Shadlen, Michael N

2005-05-02

Both the speed and the accuracy of a perceptual judgment depend on the strength of the sensory stimulation. When stimulus strength is high, accuracy is high and response time is fast; when stimulus strength is low, accuracy is low and response time is slow. Although the psychometric function is well established as a tool for analyzing the relationship between accuracy and stimulus strength, the corresponding chronometric function for the relationship between response time and stimulus strength has not received as much consideration. In this article, we describe a theory of perceptual decision making based on a diffusion model. In it, a decision is based on the additive accumulation of sensory evidence over time to a bound. Combined with simple scaling assumptions, the proportional-rate and power-rate diffusion models predict simple analytic expressions for both the chronometric and psychometric functions. In a series of psychophysical experiments, we show that this theory accounts for response time and accuracy as a function of both stimulus strength and speed-accuracy instructions. In particular, the results demonstrate a close coupling between response time and accuracy. The theory is also shown to subsume the predictions of Piéron's Law, a power function dependence of response time on stimulus strength. The theory's analytic chronometric function allows one to extend theories of accuracy to response time.

Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel

PubMed Central

Kyogoku, Noriaki; Ikeda, Hiroaki; Tsuchikawa, Takahiro; Abiko, Takehiro; Fujiwara, Aki; Maki, Takehiro; Yamamura, Yoshiyuki; Ichinokawa, Masaomi; Tanaka, Kimitaka; Imai, Naoko; Miyahara, Yoshihiro; Kageyama, Shinichi; Shiku, Hiroshi; Hirano, Satoshi

2016-01-01

A phase I+II clinical trial of vaccination with MAGE-A4 protein complexed with cholesteryl pullulan melanoma antigen gene-A4 nanogel (CHP-MAGE-A4) is currently underway in patients with MAGE-A4-expressing cancer. In the present study, the primary phase I endpoint was to test the safety of the administration of 300 µg CHP-MAGE-A4 with and without OK-432. Another aim of the study was to clarify the details of the specific humoral immune response to vaccination. The 9 patients enrolled for phase I were vaccinated 6 times, once every 2 weeks: 3 patients with 100 µg and 3 patients with 300 µg CHP-MAGE-A4, and 3 patients with 300 µg CHP-MAGE-A4 plus 0.5 clinical units of OK-432. Toxicities were assessed using Common Terminology Criteria for Adverse Events v3.0. Clinical response was evaluated by modified Response Evaluation Criteria in Solid Tumours. Immunological monitoring of anti-MAGE-A4-specific antibodies was performed by ELISA of pre- and post-vaccination patient sera. The 6 vaccinations produced no severe adverse events. Stable disease was assessed in 4/9 patients. Anti-MAGE-A4 total immunoglobulin (Ig)G titers increased in 7/9 patients. Efficacious anti-MAGE-A4 IgG1, 2 and 3 antibody responses were observed in 7/9 patients. Among them, positive conversions to T helper 2 (Th2)-type antibody responses (IgG4 and IgE) were observed after frequent vaccination in 4/7 patients. The Th2 conversion was possibly associated with undesirable clinical observations, including progressive disease and the appearance of a new relapse lesion. The present study suggested that frequent vaccinations activated a Th2-dominant status in the cancer patients. The identification of a time-dependent IgG subclass and IgE antibody production during vaccination protocols may be a useful surrogate marker indicating a potentially undesirable change of the immunological environment for an effective antitumor immune response in cancer patients. PMID:28105158

Methane fluxes show consistent temperature dependence across microbial to ecosystem scales.

PubMed

Yvon-Durocher, Gabriel; Allen, Andrew P; Bastviken, David; Conrad, Ralf; Gudasz, Cristian; St-Pierre, Annick; Thanh-Duc, Nguyen; del Giorgio, Paul A

2014-03-27

Methane (CH4) is an important greenhouse gas because it has 25 times the global warming potential of carbon dioxide (CO2) by mass over a century. Recent calculations suggest that atmospheric CH4 emissions have been responsible for approximately 20% of Earth's warming since pre-industrial times. Understanding how CH4 emissions from ecosystems will respond to expected increases in global temperature is therefore fundamental to predicting whether the carbon cycle will mitigate or accelerate climate change. Methanogenesis is the terminal step in the remineralization of organic matter and is carried out by strictly anaerobic Archaea. Like most other forms of metabolism, methanogenesis is temperature-dependent. However, it is not yet known how this physiological response combines with other biotic processes (for example, methanotrophy, substrate supply, microbial community composition) and abiotic processes (for example, water-table depth) to determine the temperature dependence of ecosystem-level CH4 emissions. It is also not known whether CH4 emissions at the ecosystem level have a fundamentally different temperature dependence than other key fluxes in the carbon cycle, such as photosynthesis and respiration. Here we use meta-analyses to show that seasonal variations in CH4 emissions from a wide range of ecosystems exhibit an average temperature dependence similar to that of CH4 production derived from pure cultures of methanogens and anaerobic microbial communities. This average temperature dependence (0.96 electron volts (eV)), which corresponds to a 57-fold increase between 0 and 30°C, is considerably higher than previously observed for respiration (approximately 0.65 eV) and photosynthesis (approximately 0.3 eV). As a result, we show that both the emission of CH4 and the ratio of CH4 to CO2 emissions increase markedly with seasonal increases in temperature. Our findings suggest that global warming may have a large impact on the relative contributions of CO2 and CH4 to total greenhouse gas emissions from aquatic ecosystems, terrestrial wetlands and rice paddies.

Lagrangian descriptors in dissipative systems.

PubMed

Junginger, Andrej; Hernandez, Rigoberto

2016-11-09

The reaction dynamics of time-dependent systems can be resolved through a recrossing-free dividing surface associated with the transition state trajectory-that is, the unique trajectory which is bound to the barrier region for all time in response to a given time-dependent potential. A general procedure based on the minimization of Lagrangian descriptors has recently been developed by Craven and Hernandez [Phys. Rev. Lett., 2015, 115, 148301] to construct this particular trajectory without requiring perturbative expansions relative to the naive transition state point at the top of the barrier. The extension of the method to account for dissipation in the equations of motion requires additional considerations established in this paper because the calculation of the Lagrangian descriptor involves the integration of trajectories in forward and backward time. The two contributions are in general very different because the friction term can act as a source (in backward time) or sink (in forward time) of energy, leading to the possibility that information about the phase space structure may be lost due to the dominance of only one of the terms. To compensate for this effect, we introduce a weighting scheme within the Lagrangian descriptor and demonstrate that for thermal Langevin dynamics it preserves the essential phase space structures, while they are lost in the nonweighted case.

Theory of ion-matrix-sheath dynamics

NASA Astrophysics Data System (ADS)

Kos, L.; Tskhakaya, D. D.

2018-01-01

The time evolution of a one-dimensional, uni-polar ion sheath (an "ion matrix sheath") is investigated. The analytical solutions for the ion-fluid and Poisson's equations are found for an arbitrary time dependence of the wall-applied negative potential. In the case that the wall potential is large and remains constant after its ramp-up application, the explicit time dependencies of the sheath's parameters during the initial stage of the process are given. The characteristic rate of approaching the stationary state, satisfying the Child-Langmuir law, is determined.

Conditional Dependence between Response Time and Accuracy: An Overview of its Possible Sources and Directions for Distinguishing between Them

PubMed Central

Bolsinova, Maria; Tijmstra, Jesper; Molenaar, Dylan; De Boeck, Paul

2017-01-01

With the widespread use of computerized tests in educational measurement and cognitive psychology, registration of response times has become feasible in many applications. Considering these response times helps provide a more complete picture of the performance and characteristics of persons beyond what is available based on response accuracy alone. Statistical models such as the hierarchical model (van der Linden, 2007) have been proposed that jointly model response time and accuracy. However, these models make restrictive assumptions about the response processes (RPs) that may not be realistic in practice, such as the assumption that the association between response time and accuracy is fully explained by taking speed and ability into account (conditional independence). Assuming conditional independence forces one to ignore that many relevant individual differences may play a role in the RPs beyond overall speed and ability. In this paper, we critically consider the assumption of conditional independence and the important ways in which it may be violated in practice from a substantive perspective. We consider both conditional dependences that may arise when all persons attempt to solve the items in similar ways (homogeneous RPs) and those that may be due to persons differing in fundamental ways in how they deal with the items (heterogeneous processes). The paper provides an overview of what we can learn from observed conditional dependences. We argue that explaining and modeling these differences in the RPs is crucial to increase both the validity of measurement and our understanding of the relevant RPs. PMID:28261136

Filter frequency response of time dependent signal using Laplace transform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shestakov, Aleksei I.

We analyze the effect a filter has on a time dependent signal x(t). If X(s) is the Laplace transform of x and H (s) is the filter Transfer function, the response in frequency space is X (s) H (s). Consequently, in real space, the response is the convolution (x*h) (t), where hi is the Laplace inverse of H. Effects are analyzed and analytically for functions such as (t/t c) 2 e -t/tmore » $$_c$$, where t c = const. We consider lowpass, highpass and bandpass filters.« less

Profiling CCK-mediated pancreatic growth: the dynamic genetic program and the role of STATs as potential regulators.

PubMed

Gurda, Grzegorz T; Wang, Jackie Y; Guo, LiLi; Ernst, Stephen A; Williams, John A

2012-01-18

Feeding mice with protease inhibitor (PI) leads to increased endogenous cholecystokinin (CCK) release and results in pancreatic growth. This adaptive response requires calcineurin (CN)-NFAT and AKT-mTOR pathways, but the genes involved, the dynamics of their expression, and other regulatory pathways remain unknown. Here, we examined the early (1-8 h) transcriptional program that underlies pancreatic growth. We found 314 upregulated and 219 downregulated genes with diverse temporal and functional profiles. Several new identifications include the following: stress response genes Gdf15 and Txnip, metabolic mediators Pitpnc1 and Hmges2, as well as components of growth factor response Fgf21, Atf3, and Egr1. The genes fell into seven self-organizing clusters, each with a distinct pattern of expression; a representative gene within each of the upregulated clusters (Egr1, Gadd45b, Rgs2, and Serpinb1a) was validated by qRT-PCR. Genes up at any point throughout the time course and CN-dependent genes were subjected to further bioinformatics-based networking and promoter analysis, yielding STATs as potential transcriptional regulators. As shown by PCR, qPCR, and Western blots, the active phospho-form of STAT3 and the Jak-STAT feedback inhibitor Socs2 were both increased throughout early pancreatic growth. Moreover, immunohistochemistry showed a CCK-dependent and acinar cell-specific increase in nuclear localization of p-STAT3, with >75% nuclear occupancy in PI-fed mice vs. <0.1% in controls. Thus, the study identified novel genes likely to be important for CCK-driven pancreatic growth, characterized and biologically validated the dynamic pattern of their expression and investigated STAT-Socs signaling as a new player in this trophic response.

Focused microwave irradiation-assisted immunohistochemistry to study effects of ketamine on phospho-ERK expression in the mouse brain.

PubMed

Fernandes, Alda; Li, Yu-Wen

2017-09-01

Ketamine produces rapid and long-lasting antidepressant effects in depressive patients. Preclinical studies demonstrate that ketamine stimulates AMPA receptor transmission and activates BDNF/TrkB-Akt/ERK-mTOR signaling cascades, leading to a sustained increase in synaptic protein synthesis and strengthening of synaptic plasticity, a potential mechanism underlying the antidepressant effects. The purpose of this study was to develop an immunohistochemistry (IHC) assay to map the distribution of extracellular signal-regulated kinase (ERK) phosphorylation in the mouse brain in response to systemic ketamine treatment. We established a focused microwave irradiation-assisted IHC assay to detect phosphorylated (phospho) proteins including phospho-ERK, phospho- cAMP-response- element-binding protein (CREB), phospho- glutamate receptor 1 (GluR1) and phospho- calcium/calmodulin-dependent protein kinase II (CaMKII) with greater sensitivity and reproducibility in comparison to conventional IHC methods. A single dose of ketamine produced a robust, dose- and time-dependent increase in phospho-ERK immunoreactive (phospho-ERK-ir) neurons in the medial prefrontal cortex (mPFC) and the central nucleus of the amygdala. Phospho-ERK-ir neurons in the mPFC were primarily located in the prelimbic and anterior cingulate subregions with the morphology resembling pyramidal neurons. An increase in phospho-ERK-ir was also observed in the brainstem dorsal raphe nucleus and locus coeruleus. The NMDA GluN2B subtype receptor antagonist Ro 25-6981 increased phospho-ERK expression in the brain in a similar pattern as ketamine. In summary, we have established a sensitive and reliable focused microwave irradiation-assisted IHC assay, and defined the activation pattern of ERK, in response to systemic ketamine and Ro 25-6981 treatment, in brain regions that are potentially responsible for mediating the antidepressant effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Spatially varying density dependence drives a shifting mosaic of survival in a recovering apex predator (Canis lupus).

PubMed

O'Neil, Shawn T; Bump, Joseph K; Beyer, Dean E

2017-11-01

Understanding landscape patterns in mortality risk is crucial for promoting recovery of threatened and endangered species. Humans affect mortality risk in large carnivores such as wolves ( Canis lupus ), but spatiotemporally varying density dependence can significantly influence the landscape of survival. This potentially occurs when density varies spatially and risk is unevenly distributed. We quantified spatiotemporal sources of variation in survival rates of gray wolves ( C. lupus ) during a 21-year period of population recovery in the Upper Peninsula of Michigan, USA. We focused on mapping risk across time using Cox Proportional Hazards (CPH) models with time-dependent covariates, thus exploring a shifting mosaic of survival. Extended CPH models and time-dependent covariates revealed influences of seasonality, density dependence and experience, as well as individual-level factors and landscape predictors of risk. We used results to predict the shifting landscape of risk at the beginning, middle, and end of the wolf recovery time series. Survival rates varied spatially and declined over time. Long-term change was density-dependent, with landscape predictors such as agricultural land cover and edge densities contributing negatively to survival. Survival also varied seasonally and depended on individual experience, sex, and resident versus transient status. The shifting landscape of survival suggested that increasing density contributed to greater potential for human conflict and wolf mortality risk. Long-term spatial variation in key population vital rates is largely unquantified in many threatened, endangered, and recovering species. Variation in risk may indicate potential for source-sink population dynamics, especially where individuals preemptively occupy suitable territories, which forces new individuals into riskier habitat types as density increases. We encourage managers to explore relationships between adult survival and localized changes in population density. Density-dependent risk maps can identify increasing conflict areas or potential habitat sinks which may persist due to high recruitment in adjacent habitats.

Dynamic Fluid Flow Mechanical Stimulation Modulates Bone Marrow Mesenchymal Stem Cells.

PubMed

Hu, Minyi; Yeh, Robbin; Lien, Michelle; Teeratananon, Morgan; Agarwal, Kunal; Qin, Yi-Xian

2013-03-01

Osteoblasts are derived from mesenchymal stem cells (MSCs), which initiate and regulate bone formation. New strategies for osteoporosis treatments have aimed to control the fate of MSCs. While functional disuse decreases MSC growth and osteogenic potentials, mechanical signals enhance MSC quantity and bias their differentiation toward osteoblastogenesis. Through a non-invasive dynamic hydraulic stimulation (DHS), we have found that DHS can mitigate trabecular bone loss in a functional disuse model via rat hindlimb suspension (HLS). To further elucidate the downstream cellular effect of DHS and its potential mechanism underlying the bone quality enhancement, a longitudinal in vivo study was designed to evaluate the MSC populations in response to DHS over 3, 7, 14, and 21 days. Five-month old female Sprague Dawley rats were divided into three groups for each time point: age-matched control, HLS, and HLS+DHS. DHS was delivered to the right mid-tibiae with a daily "10 min on-5 min off-10 min on" loading regime for five days/week. At each sacrifice time point, bone marrow MSCs of the stimulated and control tibiae were isolated through specific cell surface markers and quantified by flow cytometry analysis. A strong time-dependent manner of bone marrow MSC induction was observed in response to DHS, which peaked on day 14. After 21 days, this effect of DHS was diminished. This study indicates that the MSC pool is positively influenced by the mechanical signals driven by DHS. Coinciding with our previous findings of mitigation of disuse bone loss, DHS induced changes in MSC number may bias the differentiation of the MSC population towards osteoblastogenesis, thereby promoting bone formation under disuse conditions. This study provides insights into the mechanism of time-sensitive MSC induction in response to mechanical loading, and for the optimal design of osteoporosis treatments.

Evaluation of the Absolute Regional Temperature Potential

NASA Technical Reports Server (NTRS)

Shindell, D. T.

2012-01-01

The Absolute Regional Temperature Potential (ARTP) is one of the few climate metrics that provides estimates of impacts at a sub-global scale. The ARTP presented here gives the time-dependent temperature response in four latitude bands (90-28degS, 28degS-28degN, 28-60degN and 60-90degN) as a function of emissions based on the forcing in those bands caused by the emissions. It is based on a large set of simulations performed with a single atmosphere-ocean climate model to derive regional forcing/response relationships. Here I evaluate the robustness of those relationships using the forcing/response portion of the ARTP to estimate regional temperature responses to the historic aerosol forcing in three independent climate models. These ARTP results are in good accord with the actual responses in those models. Nearly all ARTP estimates fall within +/-20%of the actual responses, though there are some exceptions for 90-28degS and the Arctic, and in the latter the ARTP may vary with forcing agent. However, for the tropics and the Northern Hemisphere mid-latitudes in particular, the +/-20% range appears to be roughly consistent with the 95% confidence interval. Land areas within these two bands respond 39-45% and 9-39% more than the latitude band as a whole. The ARTP, presented here in a slightly revised form, thus appears to provide a relatively robust estimate for the responses of large-scale latitude bands and land areas within those bands to inhomogeneous radiative forcing and thus potentially to emissions as well. Hence this metric could allow rapid evaluation of the effects of emissions policies at a finer scale than global metrics without requiring use of a full climate model.

Universal time-dependent dispersion properties for diffusion in a one-dimensional critically tilted potential.

PubMed

Guérin, T; Dean, D S

2017-01-01

We consider the time-dependent dispersion properties of overdamped tracer particles diffusing in a one-dimensional periodic potential under the influence of an additional constant tilting force F. The system is studied in the region where the force is close to the critical value F_{c} at which the barriers separating neighboring potential wells disappear. We show that, when F crosses the critical value, the shape of the mean-square displacement (MSD) curves is strongly modified. We identify a diffusive regime at intermediate-time scales with an effective diffusion coefficient which is much larger than the late-time diffusion coefficient for F>F_{c}, whereas for F

The Arabidopsis SUMO E3 ligase SIZ1 mediates the temperature dependent trade-off between plant immunity and growth

PubMed Central

Vlachakis, Georgios; Chatterjee, Sayantani; Arroyo-Mateos, Manuel; Wackers, Paul F. K.; Jonker, Martijs J.

2018-01-01

Increased ambient temperature is inhibitory to plant immunity including auto-immunity. SNC1-dependent auto-immunity is, for example, fully suppressed at 28°C. We found that the Arabidopsis sumoylation mutant siz1 displays SNC1-dependent auto-immunity at 22°C but also at 28°C, which was EDS1 dependent at both temperatures. This siz1 auto-immune phenotype provided enhanced resistance to Pseudomonas at both temperatures. Moreover, the rosette size of siz1 recovered only weakly at 28°C, while this temperature fully rescues the growth defects of other SNC1-dependent auto-immune mutants. This thermo-insensitivity of siz1 correlated with a compromised thermosensory growth response, which was independent of the immune regulators PAD4 or SNC1. Our data reveal that this high temperature induced growth response strongly depends on COP1, while SIZ1 controls the amplitude of this growth response. This latter notion is supported by transcriptomics data, i.e. SIZ1 controls the amplitude and timing of high temperature transcriptional changes including a subset of the PIF4/BZR1 gene targets. Combined our data signify that SIZ1 suppresses an SNC1-dependent resistance response at both normal and high temperatures. At the same time, SIZ1 amplifies the dark and high temperature growth response, likely via COP1 and upstream of gene regulation by PIF4 and BRZ1. PMID:29357355

Glucose sensing by GABAergic neurons in the mouse nucleus tractus solitarii

PubMed Central

Boychuk, Carie R.; Gyarmati, Peter; Xu, Hong

2015-01-01

Changes in blood glucose concentration alter autonomic function in a manner consistent with altered neural activity in brain regions controlling digestive processes, including neurons in the brain stem nucleus tractus solitarii (NTS), which process viscerosensory information. With whole cell or on-cell patch-clamp recordings, responses to elevating glucose concentration from 2.5 to 15 mM were assessed in identified GABAergic NTS neurons in slices from transgenic mice that express EGFP in a subset of GABA neurons. Single-cell real-time RT-PCR was also performed to detect glutamic acid decarboxylase (GAD67) in recorded neurons. In most identified GABA neurons (73%), elevating glucose concentration from 2.5 to 15 mM resulted in either increased (40%) or decreased (33%) neuronal excitability, reflected by altered membrane potential and/or action potential firing. Effects on membrane potential were maintained when action potentials or fast synaptic inputs were blocked, suggesting direct glucose sensing by GABA neurons. Glucose-inhibited GABA neurons were found predominantly in the lateral NTS, whereas glucose-excited cells were mainly in the medial NTS, suggesting regional segregation of responses. Responses were prevented in the presence of glucosamine, a glucokinase (GCK) inhibitor. Depolarizing responses were prevented when KATP channel activity was blocked with tolbutamide. Whereas effects on synaptic input to identified GABAergic neurons were variable in GABA neurons, elevating glucose increased glutamate release subsequent to stimulation of tractus solitarius in unlabeled, unidentified neurons. These results indicate that GABAergic NTS neurons act as GCK-dependent glucose sensors in the vagal complex, providing a means of modulating central autonomic signals when glucose is elevated. PMID:26084907

Partition-free theory of time-dependent current correlations in nanojunctions in response to an arbitrary time-dependent bias

NASA Astrophysics Data System (ADS)

Ridley, Michael; MacKinnon, Angus; Kantorovich, Lev

2017-04-01

Working within the nonequilibrium Green's function formalism, a formula for the two-time current correlation function is derived for the case of transport through a nanojunction in response to an arbitrary time-dependent bias. The one-particle Hamiltonian and the wide-band limit approximation are assumed, enabling us to extract all necessary Green's functions and self-energies for the system, extending the analytic work presented previously [Ridley et al., Phys. Rev. B 91, 125433 (2015), 10.1103/PhysRevB.91.125433]. We show that our expression for the two-time correlation function generalizes the Büttiker theory of shot and thermal noise on the current through a nanojunction to the time-dependent bias case including the transient regime following the switch-on. Transient terms in the correlation function arise from an initial state that does not assume (as is usually done) that the system is initially uncoupled, i.e., our approach is partition free. We show that when the bias loses its time dependence, the long-time limit of the current correlation function depends on the time difference only, as in this case an ideal steady state is reached. This enables derivation of known results for the single-frequency power spectrum and for the zero-frequency limit of this power spectrum. In addition, we present a technique which facilitates fast calculations of the transient quantum noise, valid for arbitrary temperature, time, and voltage scales. We apply this formalism to a molecular wire system for both dc and ac biases, and find a signature of the traversal time for electrons crossing the wire in the time-dependent cross-lead current correlations.

Dengue Virus Modulates the Unfolded Protein Response in a Time-dependent Manner*

PubMed Central

Peña, José; Harris, Eva

2011-01-01

Flaviviruses, such as dengue virus (DENV), depend on the host endoplasmic reticulum for translation, replication, and packaging of their genomes. Here we report that DENV-2 infection modulates the unfolded protein response in a time-dependent manner. We show that early DENV-2 infection triggers and then suppresses PERK-mediated eIF2α phosphorylation and that in mid and late DENV-2 infection, the IRE1-XBP1 and ATF6 pathways are activated, respectively. Activation of IRE1-XBP1 correlated with induction of downstream targets GRP78, CHOP, and GADD34. Furthermore, induction of CHOP did not induce apoptotic markers, such as suppression of anti-apoptotic protein Bcl-2, activation of caspase-9 or caspase-3, and cleavage of poly(ADP-ribose) polymerase. Finally, we show that DENV-2 replication is affected in PERK−/− and IRE1−/− mouse embryo fibroblasts when compared with wild-type mouse embryo fibroblasts. These results demonstrate that time-dependent activation of the unfolded protein response by DENV-2 can override inhibition of translation, prevent apoptosis, and prolong the viral life cycle. PMID:21385877

Dose and Time Dependencies in Stress Pathway Responses during Chemical Exposure: Novel Insights from Gene Regulatory Networks.

PubMed

Souza, Terezinha M; Kleinjans, Jos C S; Jennen, Danyel G J

2017-01-01

Perturbation of biological networks is often observed during exposure to xenobiotics, and the identification of disturbed processes, their dynamic traits, and dose-response relationships are some of the current challenges for elucidating the mechanisms determining adverse outcomes. In this scenario, reverse engineering of gene regulatory networks (GRNs) from expression data may provide a system-level snapshot embedded within accurate molecular events. Here, we investigate the composition of GRNs inferred from groups of chemicals with two distinct outcomes, namely carcinogenicity [azathioprine (AZA) and cyclophosphamide (CYC)] and drug-induced liver injury (DILI; diclofenac, nitrofurantoin, and propylthiouracil), and a non-carcinogenic/non-DILI group (aspirin, diazepam, and omeprazole). For this, we analyzed publicly available exposed in vitro human data, taking into account dose and time dependencies. Dose-Time Network Identification (DTNI) was applied to gene sets from exposed primary human hepatocytes using four stress pathways, namely endoplasmic reticulum (ER), NF-κB, NRF2, and TP53. Inferred GRNs suggested case specificity, varying in interactions, starting nodes, and target genes across groups. DILI and carcinogenic compounds were shown to directly affect all pathway-based GRNs, while non-DILI/non-carcinogenic chemicals only affected NF-κB. NF-κB-based GRNs clearly illustrated group-specific disturbances, with the cancer-related casein kinase CSNK2A1 being a target gene only in the carcinogenic group, and opposite regulation of NF-κB subunits being observed in DILI and non-DILI/non-carcinogenic groups. Target genes in NRF2-based GRNs shared by DILI and carcinogenic compounds suggested markers of hepatotoxicity. Finally, we indicate several of these group-specific interactions as potentially novel. In summary, our reversed-engineered GRNs are capable of revealing dose dependent, chemical-specific mechanisms of action in stress-related biological networks.

Emerging feed-forward inhibition allows the robust formation of direction selectivity in the developing ferret visual cortex

PubMed Central

Escobar, Gina M.; Maffei, Arianna; Miller, Paul

2014-01-01

The computation of direction selectivity requires that a cell respond to joint spatial and temporal characteristics of the stimulus that cannot be separated into independent components. Direction selectivity in ferret visual cortex is not present at the time of eye opening but instead develops in the days and weeks following eye opening in a process that requires visual experience with moving stimuli. Classic Hebbian or spike timing-dependent modification of excitatory feed-forward synaptic inputs is unable to produce direction-selective cells from unselective or weakly directionally biased initial conditions because inputs eventually grow so strong that they can independently drive cortical neurons, violating the joint spatial-temporal activation requirement. Furthermore, without some form of synaptic competition, cells cannot develop direction selectivity in response to training with bidirectional stimulation, as cells in ferret visual cortex do. We show that imposing a maximum lateral geniculate nucleus (LGN)-to-cortex synaptic weight allows neurons to develop direction-selective responses that maintain the requirement for joint spatial and temporal activation. We demonstrate that a novel form of inhibitory plasticity, postsynaptic activity-dependent long-term potentiation of inhibition (POSD-LTPi), which operates in the developing cortex at the time of eye opening, can provide synaptic competition and enables robust development of direction-selective receptive fields with unidirectional or bidirectional stimulation. We propose a general model of the development of spatiotemporal receptive fields that consists of two phases: an experience-independent establishment of initial biases, followed by an experience-dependent amplification or modification of these biases via correlation-based plasticity of excitatory inputs that compete against gradually increasing feed-forward inhibition. PMID:24598528

Effects of Laser Wavelength on Ablator Testing

NASA Technical Reports Server (NTRS)

White, Susan M.

2014-01-01

Wavelength-dependent or spectral radiation effects are potentially significant for thermal protection materials. NASA atmospheric entry simulations include trajectories with significant levels of shock layer radiation which is concentrated in narrow spectral lines. Tests using two different high powered lasers, the 10.6 micron LHMEL I CO2 laser and the near-infrared 1.07 micron fiber laser, on low density ablative thermal protection materials offer a unique opportunity to evaluate spectral effects. Test results indicated that the laser wavelength can impact the thermal response of an ablative material, in terms of bond-line temperatures, penetration times, mass losses, and char layer thicknesses.

Response to ``Comment on `Excitations in photoactive molecules from quantum Monte Carlo' '' [J. Chem. Phys. 122, 087101 (2005)

NASA Astrophysics Data System (ADS)

Filippi, Claudia; Buda, Francesco

2005-02-01

We find that regions of the excited state potential energy surface of formaldimine, which are accessible from the Franck-Condon configuration, are incorrectly described by the restricted open-shell Kohn-Sham (ROKS) approach. In these regions, the deviations of the ROKS energies from the time-dependent density functional theory results are not a simple shift. Contrary to what is argued in the Comment by Doltsinis and Fink [J. Chem. Phys.XX, XXX (2004)], these differences can play a role in the excited state molecular dynamics of formaldimine at finite temperature.

Serenity: A subsystem quantum chemistry program.

PubMed

Unsleber, Jan P; Dresselhaus, Thomas; Klahr, Kevin; Schnieders, David; Böckers, Michael; Barton, Dennis; Neugebauer, Johannes

2018-05-15

We present the new quantum chemistry program Serenity. It implements a wide variety of functionalities with a focus on subsystem methodology. The modular code structure in combination with publicly available external tools and particular design concepts ensures extensibility and robustness with a focus on the needs of a subsystem program. Several important features of the program are exemplified with sample calculations with subsystem density-functional theory, potential reconstruction techniques, a projection-based embedding approach and combinations thereof with geometry optimization, semi-numerical frequency calculations and linear-response time-dependent density-functional theory. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Curchod, Basile F. E.; Agostini, Federica, E-mail: agostini@mpi-halle.mpg.de; Gross, E. K. U.

Nonadiabatic quantum interferences emerge whenever nuclear wavefunctions in different electronic states meet and interact in a nonadiabatic region. In this work, we analyze how nonadiabatic quantum interferences translate in the context of the exact factorization of the molecular wavefunction. In particular, we focus our attention on the shape of the time-dependent potential energy surface—the exact surface on which the nuclear dynamics takes place. We use a one-dimensional exactly solvable model to reproduce different conditions for quantum interferences, whose characteristic features already appear in one-dimension. The time-dependent potential energy surface develops complex features when strong interferences are present, in clear contrastmore » to the observed behavior in simple nonadiabatic crossing cases. Nevertheless, independent classical trajectories propagated on the exact time-dependent potential energy surface reasonably conserve a distribution in configuration space that mimics one of the exact nuclear probability densities.« less

An MHD simulation model of time-dependent global solar corona with temporally varying solar-surface magnetic field maps

NASA Astrophysics Data System (ADS)

Hayashi, K.

2013-11-01

We present a model of a time-dependent three-dimensional magnetohydrodynamics simulation of the sub-Alfvenic solar corona and super-Alfvenic solar wind with temporally varying solar-surface boundary magnetic field data. To (i) accommodate observational data with a somewhat arbitrarily evolving solar photospheric magnetic field as the boundary value and (ii) keep the divergence-free condition, we developed a boundary model, here named Confined Differential Potential Field model, that calculates the horizontal components of the magnetic field, from changes in the vertical component, as a potential field confined in a thin shell. The projected normal characteristic method robustly simulates the solar corona and solar wind, in response to the temporal variation of the boundary Br. We conduct test MHD simulations for two periods, from Carrington Rotation number 2009 to 2010 and from Carrington Rotation 2074 to 2075 at solar maximum and minimum of Cycle 23, respectively. We obtained several coronal features that a fixed boundary condition cannot yield, such as twisted magnetic field lines at the lower corona and the transition from an open-field coronal hole to a closed-field streamer. We also obtained slight improvements of the interplanetary magnetic field, including the latitudinal component, at Earth.

Variability of visual responses of superior colliculus neurons depends on stimulus velocity.

PubMed

Mochol, Gabriela; Wójcik, Daniel K; Wypych, Marek; Wróbel, Andrzej; Waleszczyk, Wioletta J

2010-03-03

Visually responding neurons in the superficial, retinorecipient layers of the cat superior colliculus receive input from two primarily parallel information processing channels, Y and W, which is reflected in their velocity response profiles. We quantified the time-dependent variability of responses of these neurons to stimuli moving with different velocities by Fano factor (FF) calculated in discrete time windows. The FF for cells responding to low-velocity stimuli, thus receiving W inputs, increased with the increase in the firing rate. In contrast, the dynamics of activity of the cells responding to fast moving stimuli, processed by Y pathway, correlated negatively with FF whether the response was excitatory or suppressive. These observations were tested against several types of surrogate data. Whereas Poisson description failed to reproduce the variability of all collicular responses, the inclusion of secondary structure to the generating point process recovered most of the observed features of responses to fast moving stimuli. Neither model could reproduce the variability of low-velocity responses, which suggests that, in this case, more complex time dependencies need to be taken into account. Our results indicate that Y and W channels may differ in reliability of responses to visual stimulation. Apart from previously reported morphological and physiological differences of the cells belonging to Y and W channels, this is a new feature distinguishing these two pathways.

Interdependency between Risk Assessments for Self and Other in the Field of Comparative Optimism: The Contribution of Response Times

ERIC Educational Resources Information Center

Spitzenstetter, Florence; Schimchowitsch, Sarah

2012-01-01

By introducing a response-time measure in the field of comparative optimism, this study was designed to explore how people estimate risk to self and others depending on the evaluation order (self/other or other/self). Our results show the interdependency between self and other answers. Indeed, while response time for risk assessment for the self…

Neutron star dynamics under time-dependent external torques

NASA Astrophysics Data System (ADS)

Gügercinoǧlu, Erbil; Alpar, M. Ali

2017-11-01

The two-component model describes neutron star dynamics incorporating the response of the superfluid interior. Conventional solutions and applications involve constant external torques, as appropriate for radio pulsars on dynamical time-scales. We present the general solution of two-component dynamics under arbitrary time-dependent external torques, with internal torques that are linear in the rotation rates, or with the extremely non-linear internal torques due to vortex creep. The two-component model incorporating the response of linear or non-linear internal torques can now be applied not only to radio pulsars but also to magnetars and to neutron stars in binary systems, with strong observed variability and noise in the spin-down or spin-up rates. Our results allow the extraction of the time-dependent external torques from the observed spin-down (or spin-up) time series, \\dot{Ω }(t). Applications are discussed.

Time-dependent response of filamentary composite spherical pressure vessels

NASA Technical Reports Server (NTRS)

Dozier, J. D.

1983-01-01

A filamentary composite spherical pressure vessel is modeled as a pseudoisotropic (or transversely isotropic) composite shell, with the effects of the liner and fill tubes omitted. Equations of elasticity, macromechanical and micromechanical formulations, and laminate properties are derived for the application of an internally pressured spherical composite vessel. Viscoelastic properties for the composite matrix are used to characterize time-dependent behavior. Using the maximum strain theory of failure, burst pressure and critical strain equations are formulated, solved in the Laplace domain with an associated elastic solution, and inverted back into the time domain using the method of collocation. Viscoelastic properties of HBFR-55 resin are experimentally determined and a Kevlar/HBFR-55 system is evaluated with a FORTRAN program. The computed reduction in burst pressure with respect to time indicates that the analysis employed may be used to predict the time-dependent response of a filamentary composite spherical pressure vessel.

The interaction between stress and exercise, and its impact on brain function.

PubMed

Russell, Vivienne A; Zigmond, Michael J; Dimatelis, Jacqueline J; Daniels, William M U; Mabandla, Musa V

2014-06-01

In response to acute adversity, emotional signals shift the body into a state that permits rapid detection, identification, and appropriate response to a potential threat. The stress response involves the release of a variety of substances, including neurotransmitters, neurotrophic factors, hormones, and cytokines, that enable the body to deal with the challenges of daily life. The subsequent activation of various physiological systems can be both protective and damaging to the individual, depending on timing, intensity, and duration of the stressor. Successful recovery from stressful challenges during early life leads to strengthening of synaptic connections in health-promoting neural networks and reduced vulnerability to subsequent stressors that can be protective in later life. In contrast, chronic intense uncontrollable stress can be pathogenic and lead to disorders such as depression, anxiety, hypertension, Alzheimer's disease, Parkinson's disease, and an increased toxic response to additional stressors such as traumatic brain injury and stroke. This review briefly explores the interaction between stress experienced at different stages of development and exercise later in life.

Biosensoric potential of microbial fuel cells.

PubMed

Schneider, György; Kovács, Tamás; Rákhely, Gábor; Czeller, Miklós

2016-08-01

Recent progress in microbial fuel cell (MFC) technology has highlighted the potential of these devices to be used as biosensors. The advantages of MFC-based biosensors are that they are phenotypic and can function in either assay- or flow-through formats. These features make them appropriate for contiguous on-line monitoring in laboratories and for in-field applications. The selectivity of an MFC biosensor depends on the applied microorganisms in the anodic compartment where electron transfer (ET) between the artificial surface (anode) and bacterium occurs. This process strongly determines the internal resistance of the sensoric system and thus influences signal outcome and response time. Despite their beneficial characteristics, the number of MFC-based biosensoric applications has been limited until now. The aim of this mini-review is to turn attention to the biosensoric potential of MFCs by summarizing ET mechanisms on which recently established and future sensoric devices are based.

Properties and ionic mechanisms of action potential adaptation, restitution, and accommodation in canine epicardium.

PubMed

Decker, Keith F; Heijman, Jordi; Silva, Jonathan R; Hund, Thomas J; Rudy, Yoram

2009-04-01

Computational models of cardiac myocytes are important tools for understanding ionic mechanisms of arrhythmia. This work presents a new model of the canine epicardial myocyte that reproduces a wide range of experimentally observed rate-dependent behaviors in cardiac cell and tissue, including action potential (AP) duration (APD) adaptation, restitution, and accommodation. Model behavior depends on updated formulations for the 4-aminopyridine-sensitive transient outward current (I(to1)), the slow component of the delayed rectifier K(+) current (I(Ks)), the L-type Ca(2+) channel current (I(Ca,L)), and the Na(+)-K(+) pump current (I(NaK)) fit to data from canine ventricular myocytes. We found that I(to1) plays a limited role in potentiating peak I(Ca,L) and sarcoplasmic reticulum Ca(2+) release for propagated APs but modulates the time course of APD restitution. I(Ks) plays an important role in APD shortening at short diastolic intervals, despite a limited role in AP repolarization at longer cycle lengths. In addition, we found that I(Ca,L) plays a critical role in APD accommodation and rate dependence of APD restitution. Ca(2+) entry via I(Ca,L) at fast rate drives increased Na(+)-Ca(2+) exchanger Ca(2+) extrusion and Na(+) entry, which in turn increases Na(+) extrusion via outward I(NaK). APD accommodation results from this increased outward I(NaK). Our simulation results provide valuable insight into the mechanistic basis of rate-dependent phenomena important for determining the heart's response to rapid and irregular pacing rates (e.g., arrhythmia). Accurate simulation of rate-dependent phenomena and increased understanding of their mechanistic basis will lead to more realistic multicellular simulations of arrhythmia and identification of molecular therapeutic targets.

Carbon dioxide (CO2) levels this century will alter the protein, micronutrients, and vitamin content of rice grains with potential health consequences for the poorest rice-dependent countries

PubMed Central

Zhu, Jianguo; Jiang, Qian; Xu, Xi; Liu, Gang; Ebi, Kristie L.; Drewnowski, Adam

2018-01-01

Declines of protein and minerals essential for humans, including iron and zinc, have been reported for crops in response to rising atmospheric carbon dioxide concentration, [CO2]. For the current century, estimates of the potential human health impact of these declines range from 138 million to 1.4 billion, depending on the nutrient. However, changes in plant-based vitamin content in response to [CO2] have not been elucidated. Inclusion of vitamin information would substantially improve estimates of health risks. Among crop species, rice is the primary food source for more than 2 billion people. We used multiyear, multilocation in situ FACE (free-air CO2 enrichment) experiments for 18 genetically diverse rice lines, including Japonica, Indica, and hybrids currently grown throughout Asia. We report for the first time the integrated nutritional impact of those changes (protein, micronutrients, and vitamins) for the 10 countries that consume the most rice as part of their daily caloric supply. Whereas our results confirm the declines in protein, iron, and zinc, we also find consistent declines in vitamins B1, B2, B5, and B9 and, conversely, an increase in vitamin E. A strong correlation between the impacts of elevated [CO2] on vitamin content based on the molecular fraction of nitrogen within the vitamin was observed. Finally, potential health risks associated with anticipated CO2-induced deficits of protein, minerals, and vitamins in rice were correlated to the lowest overall gross domestic product per capita for the highest rice-consuming countries, suggesting potential consequences for a global population of approximately 600 million. PMID:29806023

Carbon dioxide (CO2) levels this century will alter the protein, micronutrients, and vitamin content of rice grains with potential health consequences for the poorest rice-dependent countries.

PubMed

Zhu, Chunwu; Kobayashi, Kazuhiko; Loladze, Irakli; Zhu, Jianguo; Jiang, Qian; Xu, Xi; Liu, Gang; Seneweera, Saman; Ebi, Kristie L; Drewnowski, Adam; Fukagawa, Naomi K; Ziska, Lewis H

2018-05-01

Declines of protein and minerals essential for humans, including iron and zinc, have been reported for crops in response to rising atmospheric carbon dioxide concentration, [CO 2 ]. For the current century, estimates of the potential human health impact of these declines range from 138 million to 1.4 billion, depending on the nutrient. However, changes in plant-based vitamin content in response to [CO 2 ] have not been elucidated. Inclusion of vitamin information would substantially improve estimates of health risks. Among crop species, rice is the primary food source for more than 2 billion people. We used multiyear, multilocation in situ FACE (free-air CO 2 enrichment) experiments for 18 genetically diverse rice lines, including Japonica, Indica, and hybrids currently grown throughout Asia. We report for the first time the integrated nutritional impact of those changes (protein, micronutrients, and vitamins) for the 10 countries that consume the most rice as part of their daily caloric supply. Whereas our results confirm the declines in protein, iron, and zinc, we also find consistent declines in vitamins B1, B2, B5, and B9 and, conversely, an increase in vitamin E. A strong correlation between the impacts of elevated [CO 2 ] on vitamin content based on the molecular fraction of nitrogen within the vitamin was observed. Finally, potential health risks associated with anticipated CO 2 -induced deficits of protein, minerals, and vitamins in rice were correlated to the lowest overall gross domestic product per capita for the highest rice-consuming countries, suggesting potential consequences for a global population of approximately 600 million.

Revealing Behavioral Learning Deficit Phenotypes Subsequent to In Utero Exposure to Benzo(a)pyrene

PubMed Central

McCallister, Monique M.; Li, Zhu; Zhang, Tongwen; Ramesh, Aramandla; Clark, Ryan S.; Maguire, Mark; Hutsell, Blake; Newland, M. Christopher; Hood, Darryl B.

2016-01-01

To characterize behavioral deficits in pre-adolescent offspring exposed in utero to Benzo(a)pyrene [B(a)P], timed-pregnant Long Evans Hooded rats were treated with B(a)P (150, 300, 600, and 1200 µg/kg BW) or peanut oil (vehicle) on E14, 15, 16, and 17. Following birth, during the pre-weaning period, B(a)P metabolites were examined in plasma and whole brain or cerebral cortex from exposed and control offspring. Tissue concentrations of B(a)P metabolites were (1) dose-dependent and (2) followed a time-dependence for elimination with ∼60% reduction by PND5 in the 1200 µg/kg BW experimental group. Spatial discrimination-reversal learning was utilized to evaluate potential behavioral neurotoxicity in P40–P60 offspring. Late-adolescent offspring exposed in utero to 600 and 1200 µg/kg BW were indistinguishable from their control counterparts for ability to acquire an original discrimination (OD) and reach criterion. However, a dose-dependent effect of in utero B(a)P-exposure was evident upon a discrimination reversal as exposed offspring perseverated on the previously correct response. This newly characterized behavioral deficit phenotype for the first reversal was not apparent in either the (1) OD or (2) subsequent reversal sessions relative to the respective control offspring. Furthermore, the expression of activity related-cytoskeletal-associated protein (Arc), an experience-dependent cortical protein marker known to be up-regulated in response to acquisition of a novel behavior, was greater in B(a)P-exposed offspring included in the spatial discrimination cohort versus home cage controls. Collectively, these findings support the hypothesis that in utero exposure to B(a)P during critical windows of development representing peak periods of neurogenesis results in behavioral deficits in later life. PMID:26420751

Sensitivity to timing and order in human visual cortex.

PubMed

Singer, Jedediah M; Madsen, Joseph R; Anderson, William S; Kreiman, Gabriel

2015-03-01

Visual recognition takes a small fraction of a second and relies on the cascade of signals along the ventral visual stream. Given the rapid path through multiple processing steps between photoreceptors and higher visual areas, information must progress from stage to stage very quickly. This rapid progression of information suggests that fine temporal details of the neural response may be important to the brain's encoding of visual signals. We investigated how changes in the relative timing of incoming visual stimulation affect the representation of object information by recording intracranial field potentials along the human ventral visual stream while subjects recognized objects whose parts were presented with varying asynchrony. Visual responses along the ventral stream were sensitive to timing differences as small as 17 ms between parts. In particular, there was a strong dependency on the temporal order of stimulus presentation, even at short asynchronies. From these observations we infer that the neural representation of complex information in visual cortex can be modulated by rapid dynamics on scales of tens of milliseconds. Copyright © 2015 the American Physiological Society.

Carbon nanotube-sensor-integrated microfluidic platform for real-time chemical concentration detection.

PubMed

Yang, Li; Li, Minglin; Qu, Yanli; Dong, Zaili; Li, Wen J

2009-09-01

This paper presents the development of a chemical sensor employing electronic-grade carbon nanotubes (EG-CNTs) as the active sensing element for sodium hypochlorite detection. The sensor, integrated in a PDMS-glass microfluidic chamber, was fabricated by bulk aligning of EG-CNTs between gold microelectrode pairs using dielectrophoretic technique. Upon exposure to sodium hypochlorite solution, the characteristics of the carbon nanotube chemical sensor were investigated at room temperature under constant current mode. The sensor exhibited responsivity, which fits a linear logarithmic dependence on concentration in the range of 1/32 to 8 ppm, a detection limit lower than 5 ppb, while saturating at 16 ppm. The typical response time of the sensor at room temperature is on the order of minutes and the recovery time is a few hours. In particular, the sensor showed an obvious sensitivity to the volume of detected solution. It was found that the activation power of the sensor was extremely low, i.e. in the range of nanowatts. These results indicate great potential of EG-CNT for advanced nanosensors with superior sensitivity, ultra-low power consumption, and less fabrication complexity.

Enkephalinase inhibitors potentiate tackykinin-induced release of /sup 35/SO/sub 4/-labeled macromolecules from ferret trachea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borson, D.B.; Gold, M.; Varsano, S.

1986-03-01

To study the roles of tachykinins and endogenous proteinases in regulating secretion from ferret tracheal glands, the authors measured the release of /sup 35/SO/sub 4/-labeled macromolecules after incubating segments of trachea in Ussing chambers in the presence of /sup 35/SO/sub 4/. 85% of the total macromolecular radioactivity was in fractions of molecular weights greater than or equal to 10/sup 6/. The response to substance P (SP) was concentration-dependent, with a threshold of 10/sup -9/ M, and responses to 10/sup -6/M and 10/sup -5/M of 87 +/- 9 and 156 +/- 26 pmol/cm/sup 2//h, respectively (n = 6 ea). The enkephalinasemore » inhibitor, thiorphan, increased the secretory response to SP (10/sup -6/M) in a concentration-dependent fashion, with a threshold of 10/sup -8/M, and a response to SP after 10/sup -4/M thiorphan of 268 +/- 58 pmol/cm/sup 2//h (p < 0.05; n = 6). Phosphoramidon also increased SP-induced secretion to 334 +/- 69 pmol/cm/sup 2//h (p < 0.005; n = 4), and also potentiated the secretory responses to neurokinins A and B, physalaemin, eledoisin, and kassinin, but did not potentiate the secretory responses to either bradykinin or vasoactive intestinal peptide. Other proteinase inhibitors did not potentiate SP-induced secretion. These results suggest that enkephalinase in the airway degrades tachykinins, and may therefore play a role in regulating tachykinin-induced effects.« less

Germination response of Hylocereus setaceus (Salm-Dyck ex DC: ) Ralf Bauer (Cactaceae) seeds to temperature and reduced water potentials.

PubMed

Simão, E; Takaki, M; Cardoso, V J M

2010-02-01

The germination response of Hylocereus setaceus seeds to isothermic incubation at different water potentials was analysed by using the thermal time and hydrotime models, aiming to describe some germination parameters of the population and to test the validity of the models to describe the response of the seeds to temperature and water potential. Hylocereus setaceus seeds germinated relatively well in a wide range of temperatures and the germination was rate limited from 11 to 20 degrees C interval and beyond 30 degrees C until 40 degrees C, in which the germination rate respectively shifts positively and negatively with temperature. The minimum or base temperature (T(b)) for the germination of H. setaceus was 7 degrees C, and the ceiling temperature varied nearly from 43.5 to 59 degrees C depending on the percent fraction, with median set on 49.8 degrees C. The number of degrees day necessary for 50% of the seeds to germinate in the infra-optimum temperature range was 39.3 degrees C day, whereas at the supra-optimum interval the value of theta = 77 was assumed to be constant throughout. Germination was sensitive to decreasing values of psi in the medium, and both the germinability and the germination rate shift negatively with the reduction of psi, but the rate of reduction changed with temperature. The values of base water potential (psi(b)) shift to zero with increasing temperatures and such variation reflects in the relatively greater effect of low psi on germination in supra optimum range of T. In general, the model described better the germination time courses at lower than at higher water potentials. The analysis also suggest that Tb may not be independent of psi and that psi(b(g)) may change as a function of temperature at the infra-otimum temperature range.

Observation of ultrafast temporal evolution of symmetry in short-pulsed laser induced transient states of matter (Conference Presentation)

NASA Astrophysics Data System (ADS)

Garnett, Joy; Krzyzanowska, Halina; Baydin, Andrey; Tolk, Norman H.

2017-02-01

In condensed matter physics, ultrafast photoexcitation has been shown to result in modification of macroscopic material properties, sometimes involving phase changes, on a subpicosecond time scale. In semiconductors, irreversible non-thermal solid-to-liquid structural transitions have been demonstrated at high laser fluences. In the pump-probe experiments reported here, we observe a striking continuously varying low-fluence pump-induced time-dependent structural symmetry modification in intrinsic gallium arsenide (GaAs) using a probe that produces femtosecond polarization-resolved second harmonic generation (f-PRSHG) data. SHG spectroscopy is particularly suited to monitor symmetry changes since its magnitude is governed by the nonlinear optical susceptibility tensor whose elements are determined by the underlying material symmetry. Conceptually, these experiments seek to provide insight into the details of the time evolution of symmetry arising from laser induced transient states of matter in GaAs. Overall, the basic explanation of these experimental observations is that as a result of the photoinduced electronic excitation, many electrons, including bond electrons are excited to higher states. This results in subpicosecond changes in the local anharmonic potential and produces a changing nonlinear polarization response thus accounting for the nonthermal time dependent symmetry changes. Clearly, our approach may be easily extended to many different crystalline materials with different levels of defects, dopants and stresses to fully characterize the time dependent behavior of laser induced transient states in material systems.

Laboratory-Induced Stress and Craving among Individuals with Prescription Opioid Dependence

PubMed Central

Back, Sudie E.; Gros, Daniel F.; Price, Matthew; LaRowe, Steve; Flanagan, Julianne; Brady, Kathleen T.; Davis, Charles; Jaconis, Maryanne; McCauley, Jenna L.

2015-01-01

Background Stress and conditioned drug cues have been implicated in the initiation, maintenance and relapse to substances of abuse. Although stress and drug cues are often encountered together, little research exists on whether stress potentiates the response to drug cues. Method Participants (N = 75) were 39 community recruited individuals with current prescription opioid (PO) dependence and 36 healthy controls. Participants stayed overnight in the hospital for one night and then completed laboratory testing the following morning. During laboratory testing, participants were randomly assigned to a stress task (Trier Social Stress Task; TSST) or a no-stress condition. Following the stress manipulation, all participants completed a PO cue paradigm. Immediately before and after the stress and cue tasks, the following were assessed: subjective (stress, craving, anger, sadness, happiness), physiological (heart rate, blood pressure, galvanic skin response), and neuroendocrine responses (cortisol and dehydroepiandrosterone). Results Internal validity of the stress task was demonstrated, as evidenced by significantly higher subjective stress, as well as cortisol, heart rate and blood pressure in the TSST compared to the no-stress group. Individuals with PO dependence evidenced significantly greater reactivity to the stress task than controls. Craving increased significantly in response to the drug cue task among PO participants. No stress × cue interaction was observed. Conclusions In this study, heightened stress reactivity was observed among individuals with PO dependence. Exposure to acute stress, however, did not potentiate craving in response to conditioned drug cues. PMID:26342626

Neuronal synchrony and the relation between the blood-oxygen-level dependent response and the local field potential

PubMed Central

Nguyen, Mai; Winawer, Jonathan

2017-01-01

The most widespread measures of human brain activity are the blood-oxygen-level dependent (BOLD) signal and surface field potential. Prior studies report a variety of relationships between these signals. To develop an understanding of how to interpret these signals and the relationship between them, we developed a model of (a) neuronal population responses and (b) transformations from neuronal responses into the functional magnetic resonance imaging (fMRI) BOLD signal and electrocorticographic (ECoG) field potential. Rather than seeking a transformation between the two measures directly, this approach interprets each measure with respect to the underlying neuronal population responses. This model accounts for the relationship between BOLD and ECoG data from human visual cortex in V1, V2, and V3, with the model predictions and data matching in three ways: across stimuli, the BOLD amplitude and ECoG broadband power were positively correlated, the BOLD amplitude and alpha power (8–13 Hz) were negatively correlated, and the BOLD amplitude and narrowband gamma power (30–80 Hz) were uncorrelated. The two measures provide complementary information about human brain activity, and we infer that features of the field potential that are uncorrelated with BOLD arise largely from changes in synchrony, rather than level, of neuronal activity. PMID:28742093

Time dependent response of low velocity impact induced composite conical shells under multiple delamination

NASA Astrophysics Data System (ADS)

Dey, Sudip; Karmakar, Amit

2014-02-01

This paper presents the time dependent response of multiple delaminated angle-ply composite pretwisted conical shells subjected to low velocity normal impact. The finite element formulation is based on Mindlin's theory incorporating rotary inertia and effects of transverse shear deformation. An eight-noded isoparametric plate bending element is employed to satisfy the compatibility of deformation and equilibrium of resultant forces and moments at the delamination crack front. A multipoint constraint algorithm is incorporated which leads to asymmetric stiffness matrices. The modified Hertzian contact law which accounts for permanent indentation is utilized to compute the contact force, and the time dependent equations are solved by Newmark's time integration algorithm. Parametric studies are conducted with respect to triggering parameters like laminate configuration, location of delamination, angle of twist, velocity of impactor, and impactor's displacement for centrally impacted shells.

Regression analysis of sparse asynchronous longitudinal data

PubMed Central

Cao, Hongyuan; Zeng, Donglin; Fine, Jason P.

2015-01-01

Summary We consider estimation of regression models for sparse asynchronous longitudinal observations, where time-dependent responses and covariates are observed intermittently within subjects. Unlike with synchronous data, where the response and covariates are observed at the same time point, with asynchronous data, the observation times are mismatched. Simple kernel-weighted estimating equations are proposed for generalized linear models with either time invariant or time-dependent coefficients under smoothness assumptions for the covariate processes which are similar to those for synchronous data. For models with either time invariant or time-dependent coefficients, the estimators are consistent and asymptotically normal but converge at slower rates than those achieved with synchronous data. Simulation studies evidence that the methods perform well with realistic sample sizes and may be superior to a naive application of methods for synchronous data based on an ad hoc last value carried forward approach. The practical utility of the methods is illustrated on data from a study on human immunodeficiency virus. PMID:26568699

Cytosolic increased labile Zn2+ contributes to arrhythmogenic action potentials in left ventricular cardiomyocytes through protein thiol oxidation and cellular ATP depletion.

PubMed

Degirmenci, Sinan; Olgar, Yusuf; Durak, Aysegul; Tuncay, Erkan; Turan, Belma

2018-07-01

Intracellular labile (free) Zn 2+ -level ([Zn 2+ ] i ) is low and increases markedly under pathophysiological conditions in cardiomyocytes. High [Zn 2+ ] i is associated with alterations in excitability and ionic-conductances while exact mechanisms are not clarified yet. Therefore, we examined the elevated-[Zn 2+ ] i on some sarcolemmal ionic-mechanisms, which can mediate cardiomyocyte dysfunction. High-[Zn 2+ ] i induced significant changes in action potential (AP) parameters, including depolarization in resting membrane-potential and prolongations in AP-repolarizing phases. We detected also the time-dependent effects such as induction of spontaneous APs at the time of ≥ 3 min following [Zn 2+ ] i increases, a manner of cellular ATP dependent and reversible with disulfide-reducing agent dithiothreitol, DTT. High-[Zn 2+ ] i induced inhibitions in voltage-dependent K + -channel currents, such as transient outward K + -currents, I to , steady-state currents, I ss and inward-rectifier K + -currents, I K1 , reversible with DTT seemed to be responsible from the prolongations in APs. We, for the first time, demonstrated that lowering cellular ATP level induced significant decreaeses in both I ss and I K1 , while no effect on I to . However, the increased-[Zn 2+ ] i could induce marked activation in ATP-sensitive K + -channel currents, I KATP , depending on low cellular ATP and thiol-oxidation levels of these channels. The mRNA levels of Kv4.3, Kv1.4 and Kv2.1 were depressed markedly with increased-[Zn 2+ ] i with no change in mRNA level of Kv4.2, while the mRNA level of I KATP subunit, SUR2A was increased significantly with increased-[Zn 2+ ] i , being reversible with DTT. Overall we demonstrated that high-[Zn 2+ ] i, even if nanomolar levels, alters cardiac function via prolonged APs of cardiomyocytes, at most, due to inhibitions in voltage-dependent K + -currents, although activation of I KATP is playing cardioprotective role, through some biochemical changes in cellular ATP- and thiol-oxidation levels. It seems, a well-controlled [Zn 2+ ] i can be novel therapeutic target for cardiac complications under pathological conditions including oxidative stress. Copyright © 2018 Elsevier GmbH. All rights reserved.

Sarcomere length-dependence of activity-dependent twitch potentiation in mouse skeletal muscle

PubMed Central

Rassier, Dilson E; MacIntosh, Brian R

2002-01-01

Background It has been reported that potentiation of a skeletal muscle twitch response is proportional to muscle length with a negative slope during staircase, and a positive slope during posttetanic potentiation. This study was done to directly compare staircase and posttetanic responses with measurement of sarcomere length to compare their length-dependence. Methods Mouse extensor digitorum longus (EDL) muscles were dissected to small bundles of fibers, which permit measurement of sarcomere length (SL), by laser diffraction. In vitro fixed-end contractions of EDL fiber bundles were elicited at 22°C and 35°C at sarcomere lengths ranging from 2.35 μm to 3.85 μm. Twitch contractions were assessed before and after 1.5 s of 75 Hz stimulation at 22°C or during 10 s of 10 Hz stimulation at 22°C or 35°C. Results Staircase potentiation was greater at 35°C than 22°C, and the relative magnitude of the twitch contraction (Pt*/Pt) was proportional to sarcomere length with a negative slope, over the range 2.3 μm – 3.7 μm. Linear regression yielded the following: Pt*/Pt = -0.59·SL+3.27 (r2 = 0.74); Pt*/Pt = -0.39·SL+2.34 (r2 = 0.48); and Pt*/Pt = -0.50·SL+2.45 (r2 = 0.80) for staircase at 35°C, and 22°C and posttetanic response respectively. Posttetanic depression rather than potentiation was present at long SL. This indicates that there may be two processes operating in these muscles to modulate the force: one that enhances and a second that depresses the force. Either or both of these processes may have a length-dependence of its mechanism. Conclusion There is no evidence that posttetanic potentiation is fundamentally different from staircase in these muscles. PMID:12475395

Support for the existence of invertible maps between electronic densities and non-analytic 1-body external potentials in non-relativistic time-dependent quantum mechanics

NASA Astrophysics Data System (ADS)

Mosquera, Martín A.

2017-10-01

Provided the initial state, the Runge-Gross theorem establishes that the time-dependent (TD) external potential of a system of non-relativistic electrons determines uniquely their TD electronic density, and vice versa (up to a constant in the potential). This theorem requires the TD external potential and density to be Taylor-expandable around the initial time of the propagation. This paper presents an extension without this restriction. Given the initial state of the system and evolution of the density due to some TD scalar potential, we show that a perturbative (not necessarily weak) TD potential that induces a non-zero divergence of the external force-density, inside a small spatial subset and immediately after the initial propagation time, will cause a change in the density within that subset, implying that the TD potential uniquely determines the TD density. In this proof, we assume unitary evolution of wavefunctions and first-order differentiability (which does not imply analyticity) in time of the internal and external force-densities, electronic density, current density, and their spatial derivatives over the small spatial subset and short time interval.

Where do we stand after twenty years of dynamic triggering studies? (Invited)

NASA Astrophysics Data System (ADS)

Prejean, S. G.; Hill, D. P.

2013-12-01

In the past two decades, remote dynamic triggering of earthquakes by other earthquakes has been explored in a variety of physical environments with a wide array of observation and modeling techniques. These studies have significantly refined our understanding of the state of the crust and the physical conditions controlling earthquake nucleation. Despite an ever growing database of dynamic triggering observations, significant uncertainties remain and vigorous debate in almost all aspects of the science continues. For example, although dynamic earthquake triggering can occur with peak dynamic stresses as small as 1 kPa, triggering thresholds and their dependence on local stress state, hydrological environment, and frictional properties of faults are not well understood. Some studies find a simple threshold based on the peak amplitude of shaking while others find dependencies on frequency, recharge time, and other parameters. Considerable debate remains over the range of physical processes responsible for dynamic triggering, and the wide variation in dynamic triggering responses and time scales suggests triggering by multiple physical processes. Although Coulomb shear failure with various friction laws can often explain dynamic triggering, particularly instantaneous triggering, delayed dynamic triggering may be dependent on fluid transport and other slowly evolving aseismic processes. Although our understanding of the global distribution of dynamic triggering has improved, it is far from complete due to spatially uneven monitoring. A major challenge involves establishing statistical significance of potentially triggered earthquakes, particularly if they are isolated events or time-delayed with respect to triggering stresses. Here we highlight these challenges and opportunities with existing data. We focus on environmental dependence of dynamic triggering by large remote earthquakes particularly in volcanic and geothermal systems, as these systems often have high rates of background seismicity. In many volcanic and geothermal systems, such as the Geysers in Northern California, dynamic triggering of micro-earthquakes is frequent and predictable. In contrast, most active and even erupting volcanoes in Alaska (with the exception of the Katmai Volcanic Cluster) do not experience dynamic triggering. We explore why.

Drivers for the Value of Demand Response under Increased Levels of Wind and Solar Power; NREL (National Renewable Energy Laboratory)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hale, Elaine

Demand response may be a valuable flexible resource for low-carbon electric power grids. However, there are as many types of possible demand response as there are ways to use electricity, making demand response difficult to study at scale in realistic settings. This talk reviews our state of knowledge regarding the potential value of demand response in several example systems as a function of increasing levels of wind and solar power, sometimes drawing on the analogy between demand response and storage. Overall, we find demand response to be promising, but its potential value is very system dependent. Furthermore, demand response, likemore » storage, can easily saturate ancillary service markets.« less

Simulating transient dynamics of the time-dependent time fractional Fokker-Planck systems

NASA Astrophysics Data System (ADS)

Kang, Yan-Mei

2016-09-01

For a physically realistic type of time-dependent time fractional Fokker-Planck (FP) equation, derived as the continuous limit of the continuous time random walk with time-modulated Boltzmann jumping weight, a semi-analytic iteration scheme based on the truncated (generalized) Fourier series is presented to simulate the resultant transient dynamics when the external time modulation is a piece-wise constant signal. At first, the iteration scheme is demonstrated with a simple time-dependent time fractional FP equation on finite interval with two absorbing boundaries, and then it is generalized to the more general time-dependent Smoluchowski-type time fractional Fokker-Planck equation. The numerical examples verify the efficiency and accuracy of the iteration method, and some novel dynamical phenomena including polarized motion orientations and periodic response death are discussed.

The delayed rectifier potassium conductance in the sarcolemma and the transverse tubular system membranes of mammalian skeletal muscle fibers

PubMed Central

DiFranco, Marino; Quinonez, Marbella

2012-01-01

A two-microelectrode voltage clamp and optical measurements of membrane potential changes at the transverse tubular system (TTS) were used to characterize delayed rectifier K currents (IKV) in murine muscle fibers stained with the potentiometric dye di-8-ANEPPS. In intact fibers, IKV displays the canonical hallmarks of KV channels: voltage-dependent delayed activation and decay in time. The voltage dependence of the peak conductance (gKV) was only accounted for by double Boltzmann fits, suggesting at least two channel contributions to IKV. Osmotically treated fibers showed significant disconnection of the TTS and displayed smaller IKV, but with similar voltage dependence and time decays to intact fibers. This suggests that inactivation may be responsible for most of the decay in IKV records. A two-channel model that faithfully simulates IKV records in osmotically treated fibers comprises a low threshold and steeply voltage-dependent channel (channel A), which contributes ∼31% of gKV, and a more abundant high threshold channel (channel B), with shallower voltage dependence. Significant expression of the IKV1.4 and IKV3.4 channels was demonstrated by immunoblotting. Rectangular depolarizing pulses elicited step-like di-8-ANEPPS transients in intact fibers rendered electrically passive. In contrast, activation of IKV resulted in time- and voltage-dependent attenuations in optical transients that coincided in time with the peaks of IKV records. Normalized peak attenuations showed the same voltage dependence as peak IKV plots. A radial cable model including channels A and B and K diffusion in the TTS was used to simulate IKV and average TTS voltage changes. Model predictions and experimental data were compared to determine what fraction of gKV in the TTS accounted simultaneously for the electrical and optical data. Best predictions suggest that KV channels are approximately equally distributed in the sarcolemma and TTS membranes; under these conditions, >70% of IKV arises from the TTS. PMID:22851675

On the subsystem formulation of linear-response time-dependent DFT.

PubMed

Pavanello, Michele

2013-05-28

A new and thorough derivation of linear-response subsystem time-dependent density functional theory (TD-DFT) is presented and analyzed in detail. Two equivalent derivations are presented and naturally yield self-consistent subsystem TD-DFT equations. One reduces to the subsystem TD-DFT formalism of Neugebauer [J. Chem. Phys. 126, 134116 (2007)]. The other yields Dyson type equations involving three types of subsystem response functions: coupled, uncoupled, and Kohn-Sham. The Dyson type equations for subsystem TD-DFT are derived here for the first time. The response function formalism reveals previously hidden qualities and complications of subsystem TD-DFT compared with the regular TD-DFT of the supersystem. For example, analysis of the pole structure of the subsystem response functions shows that each function contains information about the electronic spectrum of the entire supersystem. In addition, comparison of the subsystem and supersystem response functions shows that, while the correlated response is subsystem additive, the Kohn-Sham response is not. Comparison with the non-subjective partition DFT theory shows that this non-additivity is largely an artifact introduced by the subjective nature of the density partitioning in subsystem DFT.

Numerical results for near surface time domain electromagnetic exploration: a full waveform approach

NASA Astrophysics Data System (ADS)

Sun, H.; Li, K.; Li, X., Sr.; Liu, Y., Sr.; Wen, J., Sr.

2015-12-01

Time domain or Transient electromagnetic (TEM) survey including types with airborne, semi-airborne and ground play important roles in applicants such as geological surveys, ground water/aquifer assess [Meju et al., 2000; Cox et al., 2010], metal ore exploration [Yang and Oldenburg, 2012], prediction of water bearing structures in tunnels [Xue et al., 2007; Sun et al., 2012], UXO exploration [Pasion et al., 2007; Gasperikova et al., 2009] etc. The common practice is introducing a current into a transmitting (Tx) loop and acquire the induced electromagnetic field after the current is cut off [Zhdanov and Keller, 1994]. The current waveforms are different depending on instruments. Rectangle is the most widely used excitation current source especially in ground TEM. Triangle and half sine are commonly used in airborne and semi-airborne TEM investigation. In most instruments, only the off time responses are acquired and used in later analysis and data inversion. Very few airborne instruments acquire the on time and off time responses together. Although these systems acquire the on time data, they usually do not use them in the interpretation.This abstract shows a novel full waveform time domain electromagnetic method and our recent modeling results. The benefits comes from our new algorithm in modeling full waveform time domain electromagnetic problems. We introduced the current density into the Maxwell's equation as the transmitting source. This approach allows arbitrary waveforms, such as triangle, half-sine, trapezoidal waves or scatter record from equipment, being used in modeling. Here, we simulate the establishing and induced diffusion process of the electromagnetic field in the earth. The traditional time domain electromagnetic with pure secondary fields can also be extracted from our modeling results. The real time responses excited by a loop source can be calculated using the algorithm. We analyze the full time gates responses of homogeneous half space and two layered models with half sine current waveform as examples. We find the on time responses are quite sensitive to resistivity or depth changes. The results show the potential use of full waveform responses in time domain electromagnetic surveys.

Detailed Characterization of Local Field Potential Oscillations and Their Relationship to Spike Timing in the Antennal Lobe of the Moth Manduca sexta

PubMed Central

Daly, Kevin C.; Galán, Roberto F.; Peters, Oakland J.; Staudacher, Erich M.

2011-01-01

The transient oscillatory model of odor identity encoding seeks to explain how odorants with spatially overlapped patterns of input into primary olfactory networks can be discriminated. This model provides several testable predictions about the distributed nature of network oscillations and how they control spike timing. To test these predictions, 16 channel electrode arrays were placed within the antennal lobe (AL) of the moth Manduca sexta. Unitary spiking and multi site local field potential (LFP) recordings were made during spontaneous activity and in response to repeated presentations of an odor panel. We quantified oscillatory frequency, cross correlations between LFP recording sites, and spike–LFP phase relationships. We show that odor-driven AL oscillations in Manduca are frequency modulating (FM) from ∼100 to 30 Hz; this was odorant and stimulus duration dependent. FM oscillatory responses were localized to one or two recording sites suggesting a localized (perhaps glomerular) not distributed source. LFP cross correlations further demonstrated that only a small (r < 0.05) distributed and oscillatory component was present. Cross spectral density analysis demonstrated the frequency of these weakly distributed oscillations was state dependent (spontaneous activity = 25–55 Hz; odor-driven = 55–85 Hz). Surprisingly, vector strength analysis indicated that unitary phase locking of spikes to the LFP was strongest during spontaneous activity and dropped significantly during responses. Application of bicuculline, a GABAA receptor antagonist, significantly lowered the frequency content of odor-driven distributed oscillatory activity. Bicuculline significantly reduced spike phase locking generally, but the ubiquitous pattern of increased phase locking during spontaneous activity persisted. Collectively, these results indicate that oscillations perform poorly as a stimulus-mediated spike synchronizing mechanism for Manduca and hence are incongruent with the transient oscillatory model. PMID:22046161

OK-432-stimulated chemokine secretion from human monocytes depends on MEK1/2, and involves p38 MAPK and NF-κB phosphorylation, in vitro.

PubMed

Olsnes, Carla; Bredholt, Therese; Olofsson, Jan; Aarstad, Hans J

2013-04-01

Interaction between the immune system and cancer cells allows for the use of biological response modifiers, like OK-432, in cancer therapy. We have studied the involvement of monocytes (MOs) in the immune response to OK-432 by examining MCP-1, MIP-1α and MIP-1β secretion, in vitro. OK-432-induced IL-6/TNF-α secretion has previously been shown to depend on mitogen-activated protein kinases (MAPKs) ERK1/2 and p38, and we therefore investigated the role of these MAPKs in OK-432-induced chemokine secretion. Here we demonstrate that pharmacological MEK1/2 kinase inhibition generally impaired chemokine secretion from MOs, whereas p38 MAPK inhibition in particular reduced MIP-1α production. Furthermore, simultaneous inhibition of MEK1/2 and Syk kinase was seen to have an additive impact on reduced MCP-1, MIP-1α and MIP-1β secretion. Based on single cell flow cytometry analyses, OK-432, lipoteichoic acid (LTA) and lipopolysaccharide (LPS) were seen to induce p38 MAPK and NF-κB phosphorylation in MOs with different time kinetics. LTA and LPS have been shown to induce ERK1/2 phosphorylation, whereas the levels of phosphorylated ERK1/2 remained constant following OK-432 treatment at the time points tested. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns, and we demonstrate increased TLR2 cell surface levels on the MO population, most profoundly following stimulation with LTA and OK-432. Together these results indicate that modulation of MEK1/2 and p38 MAPK signalling could affect the response to OK-432 treatment, having the potential to improve its therapeutic potential within cancer and lymphangioma treatment. © 2012 The Authors APMIS © 2012 APMIS.

Public protection - reliable allergen risk management

NASA Astrophysics Data System (ADS)

Janković, V.; Popov Raljić, J.; Đorđević, V.

2017-09-01

Consumers with potentially fatal food allergies are dependent on correct product labelling to protect their health. The food industry is responsible for providing every detail consumers need to make informed decisions. Considering public health, food suppliers have to monitor the presence of allergens, prevent cross-contamination and label products accurately. Allergen labelling of food products, drinks and non pre-packed food and drink products is clearly defined with legal regulations. To achieve this, a complete understanding of each product’s allergenic ingredients is needed and cross-contamination of food with allergens must be avoided. Raw materials need to be checked, every ingredient must be verified and every single allergen has to be stipulated. A mislabeled product could be recalled at potential cost, financially damaging business and at the same time, negatively impacting brand and reputation.

Working memory effects of gap-predictions in normal adults: an event-related potentials study.

PubMed

Hestvik, Arild; Bradley, Evan; Bradley, Catherine

2012-12-01

The current study examined the relationship between verbal memory span and the latency with which a filler-gap dependency is constructed. A previous behavioral study found that low span listeners did not exhibit antecedent reactivation at gap sites in relative clauses, in comparison to high verbal memory span subjects (Roberts et al. in J Psycholinguist Res 36(2):175-188, 2007), which suggests that low span subjects are delayed at gap filling. This possibility was examined in the current study. Using an event-related potentials paradigm, it was found that low span subjects have an onset latency delay of about 200 ms in brain responses to violations of syntactic expectancies after the gap site, thus providing a time course measure of the delay hypothesized by previous literature.

Encoding of temporal signals by the TGF-β pathway and implications for embryonic patterning

PubMed Central

Sorre, Benoit; Warmflash, Aryeh; Brivanlou, Ali H.; Siggia, Eric D.

2014-01-01

Summary Genetics and biochemistry have defined the components and wiring of the signaling pathways that pattern the embryo. Among them, the TGF-β pathway has the potential to behave as a morphogen: invitro experiments have clearly established that it can dictate cell fate in a concentration dependent manner. How morphogens convey positional information in a developing embryo, where signal levels are changing with time, is less understood. Using integrated microfluidic cell culture and time-lapse microscopy, we demonstrate here that the speed of ligand presentation has a key and previously unexpected influence on TGF-β signaling outcomes. The response to a TGF-β concentration step is transient and adaptive, slowly increasing the ligand concentration diminishes the response and well-spaced pulses of ligand combine additively resulting in greater pathway output than with constant stimulation. Our results suggest that in an embryonic context, the speed of change of ligand concentration is an instructive signal for patterning. PMID:25065773

Transference interventions and the process between therapist and patient.

PubMed

Ulberg, Randi; Amlo, Svein; Critchfield, Kenneth L; Marble, Alice; Høglend, Per

2014-06-01

Interpreting the transference has been considered a core ingredient in psychodynamic psychotherapy. The effects of analyzing the transference are probably dependent on certain characteristics of the interventions themselves and the context in which transference interventions are given. The present study describes the development and use of a therapy process rating scale (Transference Work Scale; TWS) constructed to identify, categorize, and explore work with the transference. TWS has subscales that rate timing, content, and valence of the transference interventions, as well as response from the patient. Transcribed segments (10 min) from 51 different patients were scored with TWS by 2 independent raters. The interrater agreement on the TWS items was good to excellent. Clinical examples of transference work were also rated using the Structural Analysis of Social Behavior (SASB). TWS and SASB supplement each other. TWS might be a potentially useful tool to explore the interaction of timing, category, and valence of transference work in predicting in-session patient response as well as treatment outcome. (c) 2014 APA, all rights reserved.

A direct screening procedure for gravitropism mutants in Arabidopsis thaliana (L. ) Heynh

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bullen, B.L.; Best, T.R.; Gregg, M.M.

1990-06-01

In order to isolate gravitropism mutants of Arabidopsis thaliana (L.) Heynh. var Estland for the genetic dissection of the gravitropism pathway, a direct screening procedure has been developed in which mutants are selected on the basis of their gravitropic response. Variability in hypocotyl curvature was dependent on the germination time of each seed stock, resulting in the incorrect identification of several lines as gravitropism mutants when a standard protocol for the potentiation of germination was used. When the protocol was adjusted to allow for differences in germination time, these lines were eliminated from the collection. Out of the 60,000 M2more » seedlings screened, 0.3 to 0.4% exhibited altered gravitropism. In approximately 40% of these mutant lines, only gravitropism by the root or the hypocotyl was altered, while the response of the other organ was unaffected. These data support the hypothesis that root and hypocotyl gravitropism are genetically separable.« less

An amperometric new methylene blue N-mediating sensor for hydrogen peroxide based on regenerated silk fibroin as an immobilization matrix for peroxidase.

PubMed

Qian, J; Liu, Y; Liu, H; Yu, T; Deng, J

1996-05-01

A simple and effective procedure was described for the immobilization of peroxidase in regenerated silk fibroin membrane prepared from waste silk. The membranes of regenerated silk fibroin with or without peroxidase, before or after the ethanol treatment, were characterized by ir spectra. An amperometric H202 sensor, based on the immobilized peroxidase in regenerated silk fibroin membrane, in the use of new methylene blue N as an electron transfer mediator, was fabricated. The characteristics of the sensor with respect to linearity, response time, effect of pH and temperature, stability, and reproducibility were investigated. Dependences of Michaelis-Menten constant KMapp on the concentration of the mediator, and the applied potential were also studied and the results were presented. The sensor was highly sensitive to H2O2 with a detection limit of 1.0 x 10(-7)M and with response time of less than 40 s.

Finite magnetic relaxation in x-space magnetic particle imaging: Comparison of measurements and ferrohydrodynamic models.

PubMed

Dhavalikar, R; Hensley, D; Maldonado-Camargo, L; Croft, L R; Ceron, S; Goodwill, P W; Conolly, S M; Rinaldi, C

2016-08-03

Magnetic Particle Imaging (MPI) is an emerging tomographic imaging technology that detects magnetic nanoparticle tracers by exploiting their non-linear magnetization properties. In order to predict the behavior of nanoparticles in an imager, it is possible to use a non-imaging MPI relaxometer or spectrometer to characterize the behavior of nanoparticles in a controlled setting. In this paper we explore the use of ferrohydrodynamic magnetization equations for predicting the response of particles in an MPI relaxometer. These include a magnetization equation developed by Shliomis (Sh) which has a constant relaxation time and a magnetization equation which uses a field-dependent relaxation time developed by Martsenyuk, Raikher and Shliomis (MRSh). We compare the predictions from these models with measurements and with the predictions based on the Langevin function that assumes instantaneous magnetization response of the nanoparticles. The results show good qualitative and quantitative agreement between the ferrohydrodynamic models and the measurements without the use of fitting parameters and provide further evidence of the potential of ferrohydrodynamic modeling in MPI.

Adaptive Spike Threshold Enables Robust and Temporally Precise Neuronal Encoding

PubMed Central

Resnik, Andrey; Celikel, Tansu; Englitz, Bernhard

2016-01-01

Neural processing rests on the intracellular transformation of information as synaptic inputs are translated into action potentials. This transformation is governed by the spike threshold, which depends on the history of the membrane potential on many temporal scales. While the adaptation of the threshold after spiking activity has been addressed before both theoretically and experimentally, it has only recently been demonstrated that the subthreshold membrane state also influences the effective spike threshold. The consequences for neural computation are not well understood yet. We address this question here using neural simulations and whole cell intracellular recordings in combination with information theoretic analysis. We show that an adaptive spike threshold leads to better stimulus discrimination for tight input correlations than would be achieved otherwise, independent from whether the stimulus is encoded in the rate or pattern of action potentials. The time scales of input selectivity are jointly governed by membrane and threshold dynamics. Encoding information using adaptive thresholds further ensures robust information transmission across cortical states i.e. decoding from different states is less state dependent in the adaptive threshold case, if the decoding is performed in reference to the timing of the population response. Results from in vitro neural recordings were consistent with simulations from adaptive threshold neurons. In summary, the adaptive spike threshold reduces information loss during intracellular information transfer, improves stimulus discriminability and ensures robust decoding across membrane states in a regime of highly correlated inputs, similar to those seen in sensory nuclei during the encoding of sensory information. PMID:27304526

Adaptive Spike Threshold Enables Robust and Temporally Precise Neuronal Encoding.

PubMed

Huang, Chao; Resnik, Andrey; Celikel, Tansu; Englitz, Bernhard

2016-06-01

Neural processing rests on the intracellular transformation of information as synaptic inputs are translated into action potentials. This transformation is governed by the spike threshold, which depends on the history of the membrane potential on many temporal scales. While the adaptation of the threshold after spiking activity has been addressed before both theoretically and experimentally, it has only recently been demonstrated that the subthreshold membrane state also influences the effective spike threshold. The consequences for neural computation are not well understood yet. We address this question here using neural simulations and whole cell intracellular recordings in combination with information theoretic analysis. We show that an adaptive spike threshold leads to better stimulus discrimination for tight input correlations than would be achieved otherwise, independent from whether the stimulus is encoded in the rate or pattern of action potentials. The time scales of input selectivity are jointly governed by membrane and threshold dynamics. Encoding information using adaptive thresholds further ensures robust information transmission across cortical states i.e. decoding from different states is less state dependent in the adaptive threshold case, if the decoding is performed in reference to the timing of the population response. Results from in vitro neural recordings were consistent with simulations from adaptive threshold neurons. In summary, the adaptive spike threshold reduces information loss during intracellular information transfer, improves stimulus discriminability and ensures robust decoding across membrane states in a regime of highly correlated inputs, similar to those seen in sensory nuclei during the encoding of sensory information.

Role of multisensory stimuli in vigilance enhancement- a single trial event related potential study.

PubMed

Abbasi, Nida Itrat; Bodala, Indu Prasad; Bezerianos, Anastasios; Yu Sun; Al-Nashash, Hasan; Thakor, Nitish V

2017-07-01

Development of interventions to prevent vigilance decrement has important applications in sensitive areas like transportation and defence. The objective of this work is to use multisensory (visual and haptic) stimuli for cognitive enhancement during mundane tasks. Two different epoch intervals representing sensory perception and motor response were analysed using minimum variance distortionless response (MVDR) based single trial ERP estimation to understand the performance dependency on both factors. Bereitschaftspotential (BP) latency L3 (r=0.6 in phase 1 (visual) and r=0.71 in phase 2 (visual and haptic)) was significantly correlated with reaction time as compared to that of sensory ERP latency L2 (r=0.1 in both phase 1 and phase 2). This implies that low performance in monotonous tasks is predominantly dependent on the prolonged neural interaction with the muscles to initiate movement. Further, negative relationship was found between the ERP latencies related to sensory perception and Bereitschaftspotential (BP) and occurrence of epochs when multisensory cues are provided. This means that vigilance decrement is reduced with the help of multisensory stimulus presentation in prolonged monotonous tasks.

Dynamic load synthesis for shock numerical simulation in space structure design

NASA Astrophysics Data System (ADS)

Monti, Riccardo; Gasbarri, Paolo

2017-08-01

Pyroshock loads are the most stressing environments that a space equipment experiences during its operating life from a mechanical point of view. In general, the mechanical designer considers the pyroshock analysis as a very demanding constraint. Unfortunately, due to the non-linear behaviour of the structure under such loads, only the experimental tests can demonstrate if it is able to withstand these dynamic loads. By taking all the previous considerations into account, some preliminary information about the design correctness could be done by performing ;ad-hoc; numerical simulations, for example via commercial finite element software (i.e. MSC Nastran). Usually these numerical tools face the shock solution in two ways: 1) a direct mode, by using a time dependent enforcement and by evaluating the time-response and space-response as well as the internal forces; 2) a modal basis approach, by considering a frequency dependent load and of course by evaluating internal forces in the frequency domain. This paper has the main aim to develop a numerical tool to synthetize the time dependent enforcement based on deterministic and/or genetic algorithm optimisers. In particular starting from a specified spectrum in terms of SRS (Shock Response Spectrum) a time dependent discrete function, typically an acceleration profile, will be obtained to force the equipment by simulating the shock event. The synthetizing time and the interface with standards numerical codes will be two of the main topics dealt with in the paper. In addition a congruity and consistency methodology will be presented to ensure that the identified time dependent loads fully match the specified spectrum.

Formulation and statistical optimization of self-microemulsifying drug delivery system of eprosartan mesylate for improvement of oral bioavailability.

PubMed

Dangre, Pankaj; Gilhotra, Ritu; Dhole, Shashikant

2016-10-01

The present investigation is aimed to design a statistically optimized self-microemulsifying drug delivery system (SMEDDS) of eprosartan mesylate (EM). Preliminary screening was carried out to find a suitable combination of various excipients for the formulation. A 3(2) full factorial design was employed to determine the effect of various independent variables on dependent (response) variables. The independent variables studied in the present work were concentration of oil (X 1) and the ratio of S mix (X 2), whereas the dependent variables were emulsification time (s), globule size (nm), polydispersity index (pdi), and zeta potential (mV), and the multiple linear regression analysis (MLRA) was employed to understand the influence of independent variables on dependent variables. Furthermore, a numerical optimization technique using the desirability function was used to develop a new optimized formulation with desired values of dependent variables. The optimized SMEDDS formulation of eprosartan mesylate (EMF-O) by the above method exhibited emulsification time, 118.45 ± 1.64 s; globule size, 196.81 ± 1.29 nm; zeta potential, -9.34 ± 1.2 mV, and polydispersity index, 0.354 ± 0.02. For the in vitro dissolution study, the optimized formulation (EMF-O) and pure drug were separately entrapped in the dialysis bag, and the study indicated higher release of the drug from EMF-O. In vivo pharmacokinetic studies in Wistar rats using PK solver software revealed 2.1-fold increment in oral bioavailability of EM from EMF-O, when compared with plain suspension of pure drug.

Individual differences in the recognition of facial expressions: an event-related potentials study.

PubMed

Tamamiya, Yoshiyuki; Hiraki, Kazuo

2013-01-01

Previous studies have shown that early posterior components of event-related potentials (ERPs) are modulated by facial expressions. The goal of the current study was to investigate individual differences in the recognition of facial expressions by examining the relationship between ERP components and the discrimination of facial expressions. Pictures of 3 facial expressions (angry, happy, and neutral) were presented to 36 young adults during ERP recording. Participants were asked to respond with a button press as soon as they recognized the expression depicted. A multiple regression analysis, where ERP components were set as predictor variables, assessed hits and reaction times in response to the facial expressions as dependent variables. The N170 amplitudes significantly predicted for accuracy of angry and happy expressions, and the N170 latencies were predictive for accuracy of neutral expressions. The P2 amplitudes significantly predicted reaction time. The P2 latencies significantly predicted reaction times only for neutral faces. These results suggest that individual differences in the recognition of facial expressions emerge from early components in visual processing.

The Variation of Electrochemical Cell Potentials with Temperature

ERIC Educational Resources Information Center

Peckham, Gavin D.; McNaught, Ian J.

2011-01-01

Electrochemical cell potentials have no simple relationship with temperature but depend on the interplay between the sign and magnitude of the isothermal temperature coefficient, dE[degrees]/dT, and on the magnitude of the reaction quotient, Q. The variations in possible responses of standard and non-standard cell potentials to changes in the…

Dopamine D2 receptors preferentially regulate the development of light responses of the inner retina

PubMed Central

Tian, Ning; Xu, Hong-ping; Wang, Ping

2014-01-01

Retinal light responsiveness measured via electroretinography undergoes developmental modulation and is thought to be critically regulated by both visual experience and dopamine. The primary goal of this study is to determine whether the dopamine D2 receptor regulates the visual experience-dependent functional development of the retina. Accordingly, we recorded electroretinograms from wild type mice and mice with a genetic deletion of the gene that encodes the dopamine D2 receptor raised under normal cyclic light conditions and constant darkness. Our results demonstrate that mutation of the dopamine D2 receptors preferentially increases the amplitude of the inner retinal light responses evoked by high intensity light measured as oscillatory potentials in adult mice. During postnatal development, all three major components of electroretinograms, the a-wave, b-wave and oscillatory potentials, increase with age. Comparatively, mutation of the dopamine D2 receptors preferentially reduces the age-dependent increase of b-waves evoked by low intensity light. Light deprivation from birth reduces the amplitude of b-waves and completely diminishes the increased amplitude of oscillatory potentials. Taken together, these results demonstrate that the dopamine D2 receptor plays an important role in the activity-dependent functional development of the mouse retina. PMID:25393815

Dynamic thresholds and a summary ROC curve: Assessing prognostic accuracy of longitudinal markers.

PubMed

Saha-Chaudhuri, P; Heagerty, P J

2018-04-19

Cancer patients, chronic kidney disease patients, and subjects infected with HIV are routinely monitored over time using biomarkers that represent key health status indicators. Furthermore, biomarkers are frequently used to guide initiation of new treatments or to inform changes in intervention strategies. Since key medical decisions can be made on the basis of a longitudinal biomarker, it is important to evaluate the potential accuracy associated with longitudinal monitoring. To characterize the overall accuracy of a time-dependent marker, we introduce a summary ROC curve that displays the overall sensitivity associated with a time-dependent threshold that controls time-varying specificity. The proposed statistical methods are similar to concepts considered in disease screening, yet our methods are novel in choosing a potentially time-dependent threshold to define a positive test, and our methods allow time-specific control of the false-positive rate. The proposed summary ROC curve is a natural averaging of time-dependent incident/dynamic ROC curves and therefore provides a single summary of net error rates that can be achieved in the longitudinal setting. Copyright © 2018 John Wiley & Sons, Ltd.

Integrated care for comorbid alcohol dependence and anxiety and/or depressive disorder: study protocol for an assessor-blind, randomized controlled trial.

PubMed

Morley, Kirsten C; Baillie, Andrew; Sannibale, Claudia; Teesson, Maree; Haber, Paul S

2013-11-19

A major barrier to successful treatment in alcohol dependence is psychiatric comorbidity. During treatment, the time to relapse is shorter, the drop-out rate is increased, and long-term alcohol consumption is greater for those with comorbid major depression or anxiety disorder than those with an alcohol use disorder with no comorbid mental disorder. The treatment of alcohol dependence and psychological disorders is often the responsibility of different services, and this can hinder the treatment process. Accordingly, there is a need for an effective integrated treatment for alcohol dependence and comorbid anxiety and/or depression. We aim to assess the effectiveness of a specialized, integrated intervention for alcohol dependence with comorbid anxiety and/or mood disorder using a randomized design in an outpatient hospital setting. Following a three-week stabilization period (abstinence or significantly reduced consumption), participants will undergo complete formal assessment for anxiety and depression. Those patients with a diagnosis of an anxiety and/or depressive disorder will be randomized to either 1) integrated intervention (cognitive behavioral therapy) for alcohol, anxiety, and/or depression; or 2) usual counseling care for alcohol problems. Patients will then be followed up at weeks 12, 16, and 24. The primary outcome measure is alcohol consumption (total abstinence, time to lapse, and time to relapse). Secondary outcome measures include changes in alcohol dependence severity, depression, or anxiety symptoms and changes in clinician-rated severity of anxiety and depression. The study findings will have potential implications for clinical practice by evaluating the implementation of specialized integrated treatment for comorbid anxiety and/or depression in an alcohol outpatient service. ClinicalTrials.gov Identifier: NCT01941693.

Remote sensing sensitivity to fire severity and fire recovery

USGS Publications Warehouse

Key, C.H.

2005-01-01

The paper examines fundamental ways that geospatial data on fire severity and recovery are influenced by conditions of the remote sensing. Remote sensing sensitivities are spatial, temporal and radiometric in origin. Those discussed include spatial resolution, the sampling time of year, and time since fire. For standard reference, sensitivities are demonstrated with examples drawn from an archive of burn assessments based on one radiometric index, the differenced Normalized Burn Ratio. Resolution determines the aggregation of fire effects within a pixel (alpha variation), hence defining the detected ecological response, and controlling the ability to determine patchiness and spatial distribution of responses throughout a burn (beta variation). As resolution decreases, alpha variation increases, extracting beta variation from the complexity of the whole burn. Seasonal timing impacts the radiometric quality of data in terms of transmittance, sun angle, and potential for enhanced contrast between responses within burns. Remote sensing sensitivity can degrade during many fire seasons when snow, incomplete burning, hazy conditions, low sun angles, or extended drought are common. Time since fire (lag timing) most notably shapes severity detection through the first-order fire effects evident in survivorship and delayed mortality that emerge by the growth period after fire. The former effects appear overly severe at first, but diminish, as burned vegetation remains viable. Conversely, the latter signals vegetation that appears healthy at first, but is damaged by heat to the extent that it soon dies. Both responses can lead to either over- or under-estimating severity, respectively, depending on fire behavior and pre-fire composition unique to each burned area. Based on implications of such sensitivities, three sampling intervals for short-term burn severity are identified; rapid, initial, and extended assessment, sampled within ca. two weeks, two months, and depending on the ecotype, from three months to one year after fire, respectively. Jointly, remote sensing conditions and the way burns are studied yield different tendencies for data quality and information content that impact the objectives and hypotheses that can be studied. Such considerations can be commonly overlooked, but need to be incorporated especially in comparative studies, and to build long-term reference databases on fire severity and recovery.

Community-Dwelling Cocaine-Dependent Men and Women Respond Differently to Social Stressors versus Cocaine Cues

PubMed Central

Waldrop, Angela E.; Price, Kimber L.; DeSantis, Stacia M.; Simpson, Annie N.; Back, Sudie E.; McRae, Aimee L.; Spratt, Eve G.; Kreek, Mary Jeanne; Brady, Kathleen T.

2009-01-01

Summary There are likely to be gender differences in determinants of relapse to drug use following abstinence in cocaine-dependent individuals. Cocaine-dependent women are more likely to attribute relapse to negative emotional states and interpersonal conflict. Cocaine dependence has also been linked to dysregulation of stress response and the hypothalamic pituitary adrenal (HPA) axis which may differ between genders. Subjective and HPA axis responses to a social evaluative stressor, the Trier Social Stress Test (TRIER), and in vivo cocaine-related cues were examined in the present study. Results There were no gender differences in magnitude of craving responses to the TRIER or the CUE. Both genders had a greater craving response to the CUE than to the TRIER, but the magnitude of the difference was greater for men than women (p=0.04). Cocaine-dependent subjects, compared to the control group, had significantly higher response throughout the TRIER (p<0.0001) and CUE (p<0.0001) testing sessions. There were no gender differences and no gender by cocaine interaction for ACTH responses to the TRIER, although women had lower baseline ACTH (p=0.049). On the CUE task, in contrast, female cocaine-dependent subjects had a more blunted ACTH response than did the other three groups (p=0.02). Female cocaine-dependent subjects also had a lower odds of a positive cortisol response to the TRIER as compared to the other three groups (OR=0.84, 95% CI=[0.02, 1.01]). During the CUE task, cocaine-dependent subjects had overall higher mean cortisol levels (p=0.0001), and higher odds of demonstrating a positive cortisol response to the CUE (OR=2.61, 95% CI=[1.11, 6.11]). No gender differences were found in ACTH responses to the CUE. The results are reviewed in the context of the existing literature on gender differences in cocaine dependence and potential implications for treatment are discussed. PMID:20004523

Potential biodefense model applications for portable chlorine dioxide gas production.

PubMed

Stubblefield, Jeannie M; Newsome, Anthony L

2015-01-01

Development of decontamination methods and strategies to address potential infectious disease outbreaks and bioterrorism events are pertinent to this nation's biodefense strategies and general biosecurity. Chlorine dioxide (ClO2) gas has a history of use as a decontamination agent in response to an act of bioterrorism. However, the more widespread use of ClO2 gas to meet current and unforeseen decontamination needs has been hampered because the gas is too unstable for shipment and must be prepared at the application site. Newer technology allows for easy, onsite gas generation without the need for dedicated equipment, electricity, water, or personnel with advanced training. In a laboratory model system, 2 unique applications (personal protective equipment [PPE] and animal skin) were investigated in the context of potential development of decontamination protocols. Such protocols could serve to reduce human exposure to bacteria in a decontamination response effort. Chlorine dioxide gas was capable of reducing (2-7 logs of vegetative and spore-forming bacteria), and in some instances eliminating, culturable bacteria from difficult to clean areas on PPE facepieces. The gas was effective in eliminating naturally occurring bacteria on animal skin and also on skin inoculated with Bacillus spores. The culturable bacteria, including Bacillus spores, were eliminated in a time- and dose-dependent manner. Results of these studies suggested portable, easily used ClO2 gas generation systems have excellent potential for protocol development to contribute to biodefense strategies and decontamination responses to infectious disease outbreaks or other biothreat events.

N-acetylcysteine improves coronary and peripheral vascular function.

PubMed

Andrews, N P; Prasad, A; Quyyumi, A A

2001-01-01

We investigated whether N-acetylcysteine (NAC), a reduced thiol that modulates redox state and forms adducts of nitric oxide (NO), improves endothelium-dependent vasomotion. Coronary atherosclerosis is associated with endothelial dysfunction and reduced NO activity. In 16 patients undergoing cardiac catheterization, seven with and nine without atherosclerosis, we assessed endothelium-dependent vasodilation with acetylcholine (ACH) and endothelium-independent vasodilation with nitroglycerin (NTG) and sodium nitroprusside (SNP) before and after intracoronary NAC. In 14 patients femoral vascular responses to ACH, NTG and SNP were measured before and after NAC. Intraarterial NAC did not change resting coronary or peripheral vascular tone. N-acetylcysteine potentiated ACH-mediated coronary vasodilation; coronary blood flow was 36 +/- 11% higher (p < 0.02), and epicardial diameter changed from -1.2 +/- 2% constriction to 4.7 +/- 2% dilation after NAC (p = 0.03). Acetylcholine-mediated femoral vasodilation was similarly potentiated by NAC (p = 0.001). Augmentation of the ACH response was similar in patients with or without atherosclerosis. N-acetylcysteine did not affect NTG-mediated vasodilation in either the femoral or coronary circulations and did not alter SNP responses in the femoral circulation. In contrast, coronary vasodilation with SNP was significantly greater after NAC (p < 0.05). Thiol supplementation with NAC improves human coronary and peripheral endothelium-dependent vasodilation. Nitroglycerin responses are not enhanced, but SNP-mediated responses are potentiated only in the coronary circulation. These NO-enhancing effects of thiols reflect the importance of the redox state in the control of vascular function and may be of therapeutic benefit in treating acute and chronic manifestations of atherosclerosis.

Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose response using different monomers

NASA Astrophysics Data System (ADS)

Senden, R. J.; DeJean, P.; McAuley, K. B.; Schreiner, L. J.

2006-07-01

In this work, three new polymer gel dosimeter recipes were investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomers N-isopropylacrylamide (NIPAM), diacetone acrylamide and N-vinylformamide. The new gel dosimeters studied contained gelatin (5 wt%), monomer (3 wt%), N,N'-methylene-bis-acrylamide crosslinker (3 wt%) and tetrakis (hydroxymethyl) phosphonium chloride antioxidant (10 mM). The NMR response (R2) of the dosimeters was analysed for conditions of varying dose, dose rate, time post-irradiation, and temperature during irradiation and scanning. It was shown that the dose-response behaviour of the NIPAM/Bis gel dosimeter is comparable to that of normoxic polyacrylamide gel (PAGAT) in terms of high dose-sensitivity and low dependence on dose rate and irradiation temperature, within the ranges considered. The dose-response (R2) of NIPAM/Bis appears to be linear over a greater dose range than the PAGAT gel dosimeter. The effects of time post-irradiation (temporal instability) and temperature during NMR scanning on the R2 response were more significant for NIPAM/Bis dosimeters. Diacetone acrylamide and N-vinylformamide gel dosimeters possessed considerably lower dose-sensitivities. The optical dose-response, measured in terms of the attenuation coefficient for each polymer gel dosimeter, showed potential for the use of optical imaging techniques in future studies.

Optical biosensor for environmental on-line monitoring of naphthalene and salicylate bioavailability with an immobilized bioluminescent catabolic reporter bacterium.

PubMed Central

Heitzer, A; Malachowsky, K; Thonnard, J E; Bienkowski, P R; White, D C; Sayler, G S

1994-01-01

An optical whole-cell biosensor based on a genetically engineered bioluminescent catabolic reporter bacterium was developed for continuous on-line monitoring of naphthalene and salicylate bioavailability and microbial catabolic activity potential in waste streams. The bioluminescent reporter bacterium, Pseudomonas fluorescens HK44, carries a transcriptional nahG-luxCDABE fusion for naphthalene and salicylate catabolism. Exposure to either compound resulted in inducible bioluminescence. The reporter culture was immobilized onto the surface of an optical light guide by using strontium alginate. This biosensor probe was then inserted into a measurement cell which simultaneously received the waste stream solution and a maintenance medium. Exposure under defined conditions to both naphthalene and salicylate resulted in a rapid increase in bioluminescence. The magnitude of the response and the response time were concentration dependent. Good reproducibility of the response was observed during repetitive perturbations with either naphthalene or salicylate. Exposure to other compounds, such as glucose and complex nutrient medium or toluene, resulted in either minor bioluminescence increases after significantly longer response times compared with naphthalene or no response, respectively. The environmental utility of the biosensor was tested by using real pollutant mixtures. A specific bioluminescence response was obtained after exposure to either an aqueous solution saturated with JP-4 jet fuel or an aqueous leachate from a manufactured-gas plant soil, since naphthalene was present in both pollutant mixtures. PMID:8017932

The stochastic system approach for estimating dynamic treatments effect.

PubMed

Commenges, Daniel; Gégout-Petit, Anne

2015-10-01

The problem of assessing the effect of a treatment on a marker in observational studies raises the difficulty that attribution of the treatment may depend on the observed marker values. As an example, we focus on the analysis of the effect of a HAART on CD4 counts, where attribution of the treatment may depend on the observed marker values. This problem has been treated using marginal structural models relying on the counterfactual/potential response formalism. Another approach to causality is based on dynamical models, and causal influence has been formalized in the framework of the Doob-Meyer decomposition of stochastic processes. Causal inference however needs assumptions that we detail in this paper and we call this approach to causality the "stochastic system" approach. First we treat this problem in discrete time, then in continuous time. This approach allows incorporating biological knowledge naturally. When working in continuous time, the mechanistic approach involves distinguishing the model for the system and the model for the observations. Indeed, biological systems live in continuous time, and mechanisms can be expressed in the form of a system of differential equations, while observations are taken at discrete times. Inference in mechanistic models is challenging, particularly from a numerical point of view, but these models can yield much richer and reliable results.

Opposing and following responses in sensorimotor speech control: Why responses go both ways.

PubMed

Franken, Matthias K; Acheson, Daniel J; McQueen, James M; Hagoort, Peter; Eisner, Frank

2018-06-04

When talking, speakers continuously monitor and use the auditory feedback of their own voice to control and inform speech production processes. When speakers are provided with auditory feedback that is perturbed in real time, most of them compensate for this by opposing the feedback perturbation. But some responses follow the perturbation. In the present study, we investigated whether the state of the speech production system at perturbation onset may determine what type of response (opposing or following) is made. The results suggest that whether a perturbation-related response is opposing or following depends on ongoing fluctuations of the production system: The system initially responds by doing the opposite of what it was doing. This effect and the nontrivial proportion of following responses suggest that current production models are inadequate: They need to account for why responses to unexpected sensory feedback depend on the production system's state at the time of perturbation.

Cyclopropyl glycine and proline-containing preparation noopept evoke two types of membrane potential responses in synaptoneurosomes.

PubMed

Lutsenko, V K; Vukolova, M N; Gudasheva, T A

2003-06-01

Proline, cyclo(Pro-Gly), and acyl-prolyl-containing dipeptide GVS-111 decreased synaptoneurosome membrane potential in a Ca2+-free medium. The efficiency of these preparations decreased in the following order: GVS>cyclo(Pro-Gly)>proline. Depolarization responses induced by endogenous nootropic agent cyclo(Pro-Gly) was dose-dependent and saturable; the threshold concentration of cyclo(Pro-Gly) was 10(-9) M. In a Ca2+-containing medium GVS and cyclo(Pro-Gly) induced both hyperpolarizing and depolarizing membrane responses of synaptoneurosomes. Possible mechanisms underlying changes in the membrane potential of synaptoneurosomes induced by nootropic agents are discussed. It was interesting whether modulation of electrogenesis can improve memory and potentiate the neuroprotective effect of the test nootropic agents.

Responses in Rat Core Auditory Cortex are Preserved during Sleep Spindle Oscillations

PubMed Central

Sela, Yaniv; Vyazovskiy, Vladyslav V.; Cirelli, Chiara; Tononi, Giulio; Nir, Yuval

2016-01-01

Study Objectives: Sleep is defined as a reversible state of reduction in sensory responsiveness and immobility. A long-standing hypothesis suggests that a high arousal threshold during non-rapid eye movement (NREM) sleep is mediated by sleep spindle oscillations, impairing thalamocortical transmission of incoming sensory stimuli. Here we set out to test this idea directly by examining sensory-evoked neuronal spiking activity during natural sleep. Methods: We compared neuronal (n = 269) and multiunit activity (MUA), as well as local field potentials (LFP) in rat core auditory cortex (A1) during NREM sleep, comparing responses to sounds depending on the presence or absence of sleep spindles. Results: We found that sleep spindles robustly modulated the timing of neuronal discharges in A1. However, responses to sounds were nearly identical for all measured signals including isolated neurons, MUA, and LFPs (all differences < 10%). Furthermore, in 10% of trials, auditory stimulation led to an early termination of the sleep spindle oscillation around 150–250 msec following stimulus onset. Finally, active ON states and inactive OFF periods during slow waves in NREM sleep affected the auditory response in opposite ways, depending on stimulus intensity. Conclusions: Responses in core auditory cortex are well preserved regardless of sleep spindles recorded in that area, suggesting that thalamocortical sensory relay remains functional during sleep spindles, and that sensory disconnection in sleep is mediated by other mechanisms. Citation: Sela Y, Vyazovskiy VV, Cirelli C, Tononi G, Nir Y. Responses in rat core auditory cortex are preserved during sleep spindle oscillations. SLEEP 2016;39(5):1069–1082. PMID:26856904

Immobility time during the forced swimming test predicts sensitivity to amitriptyline, whereas traveled distance in the circular corridor indicates resistance to treatment in female Wistar rats.

PubMed

Flores-Serrano, Ana G; Zaldívar-Rae, Jaime; Salgado, Humberto; Pineda, Juan C

2015-03-25

Among the main issues in the pharmacological treatment of depression are the wide variation in response to antidepressants among individual patients and the lack of indexes that allow prediction of which drug will be effective in a particular case. We evaluated whether differential sensitivity to amitriptyline is related to dichotomous categorization of individuals on the basis of their behavioral responses to two common paradigms used to evaluate the potential of tricyclic drugs as antidepressants. Hence, we categorized a cohort of 38 female rats on the basis of their immobility time in the conditioning phase of the forced swimming test [FST; high immobility (HI) vs. low immobility (LI) rats] and their locomotor behavior in the circular corridor test [high locomotor response (HR) vs. low locomotor response (LR) rats]. We subjected the rodents to the FST while under the influence of vehicle (n=20) or amitriptyline (15 mg/kg; n=18). We found no statistical evidence of dependence between categorizations of rats on the basis of their behavior in the FST and circular corridor test. Rats categorized as HI/LI and HR/LR significantly differed in their sensitivity/resistance to amitriptyline, as evidenced by changes (or lack thereof) in their immobility time, climbing time, and swimming time during the FST. These results confirm that different behavioral styles among rats are linked to differential sensitivity/resistance to antidepressants. However, we specifically found that categorizing rats as HI/LI better reflected sensitivity to amitriptyline, whereas categorizing them as HR/LR better revealed resistance to the drug. These differential responses should be considered in experimental approaches. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Peptidergic contribution to posttetanic potentiation at a central synapse of aplysia.

PubMed

Koh, Hae-Young; Weiss, Klaudiusz R

2005-08-01

Posttetanic potentiation (PTP)-like phenomena appear to be mediated by a variety of mechanisms. Although neuropeptides are located in a large number of neurons and many neuropeptides, like PTP, can enhance synaptic transmission, there is a paucity of studies indicating that peptides may actually participate in PTP. Here, we utilize a single central synapse in the feeding circuit of Aplysia to investigate a possible peptidergic contribution to PTP in the CNS. The cholinergic command-like interneuron, cerebral-buccal interneuron 2 (CBI-2), contains two neuropeptides, feeding circuit activating peptide (FCAP) and cerebral peptide 2 (CP2). Previous studies showed that tetanic prestimulation or repeated stimulation of CBI-2, as well as perfusion of FCAP and CP2, increase the size of the cholinergic excitatory postsynaptic potentials (EPSPs) that CBI-2 evokes in the motoneurons B61/62 and shorten the latency to initiate B61/62 firing in response to CBI-2 stimulation. We used temperature-dependent suppression of peptide release and occlusion experiments to examine the possible contribution of FCAP and CP2 to PTP at the CBI-2 to B61/62 synapse. When peptide release was suppressed, perfusion of exogenous peptides increased the size of posttetanic EPSPs. In contrast, when peptide release was not suppressed, exogenous peptides did not enhance the size of posttetanic EPSPs, thus indicating occlusion. Temperature manipulation and occlusion experiments also indicated that peptides extend PTP duration. This peptide-dependent prolongation of PTP has functional consequences in that it extends the duration of time during which the latency to initiate B61/62 firing in response to CBI-2 stimulation is shortened.

Kinetic assay for high-throughput screening of in vitro transthyretin amyloid fibrillogenesis inhibitors.

PubMed

Dolado, Ignacio; Nieto, Joan; Saraiva, Maria João M; Arsequell, Gemma; Valencia, Gregori; Planas, Antoni

2005-01-01

Stabilization of tetrameric transthyretin (TTR) by binding of small ligands is a current strategy aimed at inhibiting amyloid fibrillogenesis in transthyretin-associated pathologies, such as senile systemic amyloidosis (SSA) and familial amyloidotic polyneuropathy (FAP). A kinetic assay is developed for rapid evaluation of compounds as potential in vitro inhibitors in a high-throughput screening format. It is based on monitoring the time-dependent increase of absorbance due to turbidity occurring by acid-induced protein aggregation. The method uses the highly amyloidogenic Y78F mutant of human transthyretin (heterogously expressed in Escherichia coli cells). Initial rates of protein aggregation at different inhibitor concentrations follow a monoexponential dose-response curve from which inhibition parameters are calculated. For the assay development, thyroid hormones and nonsteroidal antiinflamatory drugs were chosen among other reference compounds. Some of them are already known to be in vitro inhibitors of TTR amyloidogenesis. Analysis time is optimized to last 1.5 h, and the method is implemented in microtiter plates for screening of libraries of potential fibrillogenesis inhibitors.

Coumarin-gold nanoparticle bioconjugates: preparation, antioxidant, and cytotoxic effects against MCF-7 breast cancer cells

NASA Astrophysics Data System (ADS)

Mahendran, Gokila; Ponnuchamy, Kumar

2018-05-01

In recent, the conjugation of gold nanoparticles (AuNPs) with biomolecules has shown great potential especially in disease diagnostics and treatment. Taking this in account, we report the methodology involved in the conjugation of coumarin onto the surface of citrate-capped AuNPs by a simple in situ method. Herein, we systematically performed UV-Vis spectroscopy, transmission electron microscopy, dynamic light scattering, and zeta potential measurements to characterize citrate-capped AuNPs and bioconjugates. Our results demonstrate in-depth surface chemistry of bioconjugates with improved surface plasmon resonance (529 nm), morphology (near spherical shape), hydrodynamic diameter (25.3 nm) as well as surface charge (- 35 mV). Furthermore, the bioconjugates displayed dose-dependent response in scavenging free radicals and exhibited cytotoxicity against MCF-7 breast cancer cell lines. In addition, phase-contrast microscopic analysis revealed that bioconjugates promote apoptosis in cancer cells in a time-dependent manner. Overall, we ascertain the fact that this kind of bioconjugation of AuNPs with coumarin further enhances the efficacy of inorganic nanomaterials and thus make them a better bio-therapeutic candidate.

Exercise as a Novel Treatment for Drug Addiction: A Neurobiological and Stage-Dependent Hypothesis

PubMed Central

Lynch, Wendy J.; Peterson, Alexis B.; Sanchez, Victoria; Abel, Jean; Smith, Mark A.

2013-01-01

Physical activity, and specifically exercise, has been suggested as a potential treatment for drug addiction. In this review, we discuss clinical and preclinical evidence for the efficacy of exercise at different phases of the addiction process. Potential neurobiological mechanisms are also discussed focusing on interactions with dopaminergic and glutamatergic signaling and chromatin remodeling in the reward pathway. While exercise generally produces an efficacious response, certain exercise conditions may be either ineffective or lead to detrimental effects depending on the level/type/timing of exercise exposure, the stage of addiction, the drug involved, and the subject population. During drug use initiation and withdrawal, its efficacy may be related to its ability to facilitate dopaminergic transmission, and once addiction develops, its efficacy may be related to its ability to normalize glutamatergic and dopaminergic signaling and reverse drug-induced changes in chromatin via epigenetic interactions with BDNF in the reward pathway. We conclude with future directions, including the development of exercise-based interventions alone or as an adjunct to other strategies for treating drug addiction. PMID:23806439

Predator effects on reef fish settlement depend on predator origin and recruit density.

PubMed

Benkwitt, Cassandra E

2017-04-01

During major life-history transitions, animals often experience high mortality rates due to predation, making predator avoidance particularly advantageous during these times. There is mixed evidence from a limited number of studies, however, regarding how predator presence influences settlement of coral-reef fishes and it is unknown how other potentially mediating factors, including predator origin (native vs. nonnative) or interactions among conspecific recruits, mediate the non-consumptive effects of predators on reef fish settlement. During a field experiment in the Caribbean, approximately 52% fewer mahogany snapper (Lutjanus mahogoni) recruited to reefs with a native predator (graysby grouper, Cephalopholis cruentata) than to predator-free control reefs and reefs with an invasive predator (red lionfish, Pterois volitans) regardless of predator diet. These results suggest that snapper recruits do not recognize nonnative lionfish as a threat. However, these effects depended on the density of conspecific recruits, with evidence that competition may limit the response of snapper to even native predators at the highest recruit densities. In contrast, there was no effect of predator presence or conspecific density on the recruitment of bicolor damselfish (Stegastes partitus). These context-dependent responses of coral-reef fishes to predators during settlement may influence individual survival and shape subsequent population and community dynamics. © 2017 by the Ecological Society of America.

Modeling of matter-wave solitons in a nonlinear inductor-capacitor network through a Gross-Pitaevskii equation with time-dependent linear potential

NASA Astrophysics Data System (ADS)

Kengne, E.; Lakhssassi, A.; Liu, W. M.

2017-08-01

A lossless nonlinear L C transmission network is considered. With the use of the reductive perturbation method in the semidiscrete limit, we show that the dynamics of matter-wave solitons in the network can be modeled by a one-dimensional Gross-Pitaevskii (GP) equation with a time-dependent linear potential in the presence of a chemical potential. An explicit expression for the growth rate of a purely growing modulational instability (MI) is presented and analyzed. We find that the potential parameter of the GP equation of the system does not affect the different regions of the MI. Neglecting the chemical potential in the GP equation, we derive exact analytical solutions which describe the propagation of both bright and dark solitary waves on continuous-wave (cw) backgrounds. Using the found exact analytical solutions of the GP equation, we investigate numerically the transmission of both bright and dark solitary voltage signals in the network. Our numerical studies show that the amplitude of a bright solitary voltage signal and the depth of a dark solitary voltage signal as well as their width, their motion, and their behavior depend on (i) the propagation frequencies, (ii) the potential parameter, and (iii) the amplitude of the cw background. The GP equation derived in this paper with a time-dependent linear potential opens up different ideas that may be of considerable theoretical interest for the management of matter-wave solitons in nonlinear L C transmission networks.

Food Insecurity and Chronic Disease123

PubMed Central

Laraia, Barbara A.

2013-01-01

Household food insecurity has been previously hypothesized to promote dependence on inexpensive, highly palatable foods that are energy dense. Such dependence, and the cyclical nature of having enough food in the beginning of the month followed by food scarcity at the end of the month, could lead to weight gain over a short period of time. Such dependence on energy-dense foods and weight gain may play a direct role in the development of chronic conditions. Other compounding factors that result from exposure to household food insecurity have been well described, including pathways by which stress promotes visceral fat accumulation and chronic disease. This symposium review paper summarizes the literature on the link between food insecurity and the following: 1) diet, 2) weight gain, and 3) chronic disease, especially among women. This paper also proposes a framework for considering how the lived experience of household food insecurity may potentiate the development of chronic disease by activating the stress response among individuals at critical developmental periods in a food-impoverished environment. PMID:23493536

Disruption of Fetal Hormonal Programming (Prenatal Stress) Implicates Shared Risk for Sex Differences in Depression and Cardiovascular Disease

PubMed Central

Goldstein, JM; Handa, RJ; Tobet, SA

2014-01-01

Comorbidity of major depressive disorder (MDD) and cardiovascular disease (CVD) represents the fourth leading cause of morbidity and mortality worldwide, and women have a two times greater risk than men. Thus understanding the pathophysiology has widespread implications for attenuation and prevention of disease burden. We suggest that sex-dependent MDD-CVD comorbidity may result from alterations in fetal programming consequent to the prenatal maternal environments that produce excess glucocorticoids, which then drive sex-dependent developmental alterations of the fetal hypothalamic-pituitary-adrenal (HPA) axis circuitry impacting mood, stress regulation, autonomic nervous system (ANS), and the vasculature in adulthood. Evidence is consistent with the hypothesis that disruptions of pathways associated with gamma aminobutyric acid (GABA) in neuronal and vascular development and growth factors have critical roles in key developmental periods and adult responses to injury in heart and brain. Understanding the potential fetal origins of these sex differences will contribute to development of novel sex-dependent therapeutics. PMID:24355523

Behavioral, physiological, and endocrine responses of starlings to acute increases in density.

PubMed

Nephew, Benjamin C; Romero, L Michael

2003-09-01

One potential stressor to vertebrates both in the wild and in captivity is the presence of numerous individuals in a confined space. To examine the effects of increased conspecific density in birds, we simultaneously measured cardiac, behavioral, and endocrine responses of European starlings (Sturnus vulgaris) to acute crowding. A cage containing a resident bird was outfitted with a trap door that allowed for the introduction of intruder birds (one, three, or five birds) without human interference. The resident bird was implanted with a subcutaneous heart rate (HR) transmitter, behavior was videotaped through a two-way mirror, and blood samples were taken at the end of each treatment to determine plasma corticosterone (CORT) concentrations. Resident starlings significantly increased both general activity and aggressive behaviors while decreasing preening following the initiation of elevated conspecific density. Intruder starlings increased feeding, drinking, and aggressive pecking rates, but postintrusion feeding rates decreased as intruder number increased. Preening decreased in both residents and intruders following the intrusion. HR increased in the resident starlings at the time of intruder introduction, with an increase in the magnitude of this response directly correlating with increasing intruder number. The CORT response to increased density was dependent on social role (resident or intruder), since increasing density did not alter CORT levels in resident birds, but resulted in elevated CORT 30 min following the five-intruder introduction in the intruder birds. Together, these data suggest that increased conspecific density is a significant acute stressor in starlings which is capable of inducing aggression in both residents and intruders. Furthermore, it elicits different responses from different physiological and behavioral systems, and behavioral responses such as feeding and general activity may be density-dependent. The data specifically illustrate that cardiac and behavioral activation can be independent of CORT release, and the CORT response of starlings to increased conspecific density is dependent on social role and degree of the increase in density.

Angiotensin converting enzyme inhibitors potentiate the bronchoconstriction induced by substance P in the guinea-pig.

PubMed Central

Subissi, A.; Guelfi, M.; Criscuoli, M.

1990-01-01

1. The effects of intravenous captopril and enalaprilic acid on the increase in pulmonary inflation pressure induced by different bronchoconstrictor agents were evaluated in the anaesthetized guinea-pig. 2. Captopril and enalaprilic acid (1.6-200 micrograms kg-1) enhanced dose-dependently the bronchoconstriction (BC) induced by substance P. The threshold effective dose was 1.6 micrograms kg-1 and maximal potentiation over the control response was more than 400% for both agents. Enalaprilic acid was also assayed for serum and lung angiotensin converting enzyme (ACE) inhibition in anaesthetized guinea-pigs. This drug produced a dose-dependent inhibition of ACE in both tissues, with ED50 s of 7.6 and 9.4 micrograms kg-1, respectively: this inhibitory activity was positively correlated to substance P potentiation. 3. Captopril (8-1000 micrograms kg-1) enhanced dose-dependently the BC induced by capsaicin. The threshold effective dose was 40 micrograms kg-1 and maximal potentiation about 90%. 4. Captopril (200-1000 micrograms kg-1) did not affect BC induced by bradykinin. However, this response was markedly enhanced (about 200%) by captopril 200 micrograms kg-1 in propranolol-pretreated animals. 5. Captopril and enalaprilic acid (200-1000 micrograms kg-1) slightly (20-40%) but significantly enhanced the BC induced by 5-hydroxytryptamine. However, this response was potentiated to the same extent by a dose of prazosin, which produced a degree of hypotension similar to that observed after administration of the ACE inhibitors. 6. In conclusion, ACE inhibitors potentiate the BC induced by substance P and, to a minor extent, that induced by capsaicin in the anaesthetized guinea-pig.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1697196

Insect outbreak shifts the direction of selection from fast to slow growth rates in the long-lived conifer Pinus ponderosa.

PubMed

de la Mata, Raul; Hood, Sharon; Sala, Anna

2017-07-11

Long generation times limit species' rapid evolution to changing environments. Trees provide critical global ecosystem services, but are under increasing risk of mortality because of climate change-mediated disturbances, such as insect outbreaks. The extent to which disturbance changes the dynamics and strength of selection is unknown, but has important implications on the evolutionary potential of tree populations. Using a 40-y-old Pinus ponderosa genetic experiment, we provide rare evidence of context-dependent fluctuating selection on growth rates over time in a long-lived species. Fast growth was selected at juvenile stages, whereas slow growth was selected at mature stages under strong herbivory caused by a mountain pine beetle ( Dendroctonus ponderosae ) outbreak. Such opposing forces led to no net evolutionary response over time, thus providing a mechanism for the maintenance of genetic diversity on growth rates. Greater survival to mountain pine beetle attack in slow-growing families reflected, in part, a host-based life-history trade-off. Contrary to expectations, genetic effects on tree survival were greatest at the peak of the outbreak and pointed to complex defense responses. Our results suggest that selection forces in tree populations may be more relevant than previously thought, and have implications for tree population responses to future environments and for tree breeding programs.

Cellular Response to Reagent-Free Electron-Irradiated Gelatin Hydrogels.

PubMed

Wisotzki, Emilia I; Friedrich, Ralf P; Weidt, Astrid; Alexiou, Christoph; Mayr, Stefan G; Zink, Mareike

2016-06-01

As a biomaterial, it is well established that gelatin exhibits low cytotoxicity and can promote cellular growth. However, to circumvent the potential toxicity of chemical crosslinkers, reagent-free crosslinking methods such as electron irradiation are highly desirable. While high energy irradiation has been shown to exhibit precise control over the degree of crosslinking, these hydrogels have not been thoroughly investigated for biocompatibility and degradability. Here, NIH 3T3 murine fibroblasts are seeded onto irradiated gelatin hydrogels to examine the hydrogel's influence on cellular viability and morphology. The average projected area of cells seeded onto the hydrogels increases with irradiation dose, which correlates with an increase in the hydrogel's shear modulus up to 10 kPa. Cells on these hydrogels are highly viable and exhibits normal cell cycles, particularly when compared to those grown on glutaraldehyde crosslinked gelatin hydrogels. However, proliferation is reduced on both types of crosslinked samples. To mimic the response of the hydrogels in physiological conditions, degradability is monitored in simulated body fluid to reveal strongly dose-dependent degradation times. Overall, given the low cytotoxicity, influence on cellular morphology and variability in degradation times of the electron irradiated gelatin hydrogels, there is significant potential for application in areas ranging from regenerative medicine to mechanobiology. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptor-mediated mechanism without affecting associative learning or memory retrieval mechanisms.

PubMed

Schindler, Abigail G; Li, Shuang; Chavkin, Charles

2010-08-01

Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress (FSS) before cocaine develop significantly greater conditioned place preference (CPP) for the drug-paired chamber than unstressed mice. Analysis of the dose dependency showed that FSS increased both the maximal CPP response and sensitivity to cocaine. To determine whether FSS potentiated CPP by enhancing associative learning mechanisms, mice were conditioned with cocaine in the absence of stress, then challenged after association was complete with the kappa-opioid receptor (KOR) agonist U50,488 or repeated FSS, before preference testing. Mice challenged with U50,488 60 min before CPP preference testing expressed significantly greater cocaine-CPP than saline-challenged mice. Potentiation by U50,488 was dose and time dependent and blocked by the KOR antagonist norbinaltorphimine (norBNI). Similarly, mice subjected to repeated FSS before the final preference test expressed significantly greater cocaine-CPP than unstressed controls, and FSS-induced potentiation was blocked by norBNI. Novel object recognition (NOR) performance was not affected by U50,488 given 60 min before assay, but was impaired when given 15 min before NOR assay, suggesting that KOR activation did not potentiate CPP by facilitating memory retrieval or expression. The results from this study show that the potentiation of cocaine-CPP by KOR activation does not result from an enhancement of associative learning mechanisms and that stress may instead enhance the rewarding valence of cocaine-associated cues by a dynorphin-dependent mechanism.

Brownian motion in time-dependent logarithmic potential: Exact results for dynamics and first-passage properties.

PubMed

Ryabov, Artem; Berestneva, Ekaterina; Holubec, Viktor

2015-09-21

The paper addresses Brownian motion in the logarithmic potential with time-dependent strength, U(x, t) = g(t)log(x), subject to the absorbing boundary at the origin of coordinates. Such model can represent kinetics of diffusion-controlled reactions of charged molecules or escape of Brownian particles over a time-dependent entropic barrier at the end of a biological pore. We present a simple asymptotic theory which yields the long-time behavior of both the survival probability (first-passage properties) and the moments of the particle position (dynamics). The asymptotic survival probability, i.e., the probability that the particle will not hit the origin before a given time, is a functional of the potential strength. As such, it exhibits a rather varied behavior for different functions g(t). The latter can be grouped into three classes according to the regime of the asymptotic decay of the survival probability. We distinguish 1. the regular (power-law decay), 2. the marginal (power law times a slow function of time), and 3. the regime of enhanced absorption (decay faster than the power law, e.g., exponential). Results of the asymptotic theory show good agreement with numerical simulations.

Using Necessary Information to Identify Item Dependence in Passage-Based Reading Comprehension Tests

ERIC Educational Resources Information Center

Baldonado, Angela Argo; Svetina, Dubravka; Gorin, Joanna

2015-01-01

Applications of traditional unidimensional item response theory models to passage-based reading comprehension assessment data have been criticized based on potential violations of local independence. However, simple rules for determining dependency, such as including all items associated with a particular passage, may overestimate the dependency…

The determinants of response time in a repeated constant-sum game: A robust Bayesian hierarchical dual-process model.

PubMed

Spiliopoulos, Leonidas

2018-03-01

The investigation of response time and behavior has a long tradition in cognitive psychology, particularly for non-strategic decision-making. Recently, experimental economists have also studied response time in strategic interactions, but with an emphasis on either one-shot games or repeated social-dilemmas. I investigate the determinants of response time in a repeated (pure-conflict) game, admitting a unique mixed strategy Nash equilibrium, with fixed partner matching. Response times depend upon the interaction of two decision models embedded in a dual-process framework (Achtziger and Alós-Ferrer, 2014; Alós-Ferrer, 2016). The first decision model is the commonly used win-stay/lose-shift heuristic and the second the pattern-detecting reinforcement learning model in Spiliopoulos (2013b). The former is less complex and can be executed more quickly than the latter. As predicted, conflict between these two models (i.e., each one recommending a different course of action) led to longer response times than cases without conflict. The dual-process framework makes other qualitative response time predictions arising from the interaction between the existence (or not) of conflict and which one of the two decision models the chosen action is consistent with-these were broadly verified by the data. Other determinants of RT were hypothesized on the basis of existing theory and tested empirically. Response times were strongly dependent on the actions chosen by both players in the previous rounds and the resulting outcomes. Specifically, response time was shortest after a win in the previous round where the maximum possible payoff was obtained; response time after losses was significantly longer. Strongly auto-correlated behavior (regardless of its sign) was also associated with longer response times. I conclude that, similar to other tasks, there is a strong coupling in repeated games between behavior and RT, which can be exploited to further our understanding of decision making. Copyright © 2017 Elsevier B.V. All rights reserved.

The potential benefits of repeated measure experiments for fish disease-challenge host-pathogen investigations.

PubMed

Hall, L Malcolm; Collins, Catherine; Collet, Bertrand

2018-02-02

The utility of molecular response data arising from in-vivo single and repeated measure fish disease-challenge experiments is compared. An in-silico 'experiment' involving the generation of two imaginary immune-molecule quantity response profiles over time for individual animals was carried out. Daily 'observed' molecule quantities were drawn from the 'known' individual response profiles to mimic the results of single and repeated measurement. The results indicate that repeated measure experiments are required to infer individual level response profiles, and that these experiments also provide more accurate summary statistics and data more suited to inferring the dependent ordering of the molecular response. Additionally repeated measure experiments utilise fewer animals than single measure experiments. These results are described alongside a discussion of experimental methodological issues pertinent to the adoption of aquatic animal repeated measure experimental designs. We conclude that investigators need to take particular care when making inferences from single measure experiments and that serious consideration should be given to using repeated measure experiments for in-vivo fish disease-challenge investigations. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

PM2.5-induced changes in cardiac function of hypertensive rats depend on wind direction and specific sources in Steubenville, Ohio.

PubMed

Kamal, Ali S; Rohr, Annette C; Mukherjee, Bhramar; Morishita, Masako; Keeler, Gerald J; Harkema, Jack R; Wagner, James G

2011-06-01

Increases in particulate matter less than 2.5 µm (PM(2.5)) in ambient air is linked to acute cardiovascular morbidity and mortality. Specific components and potential emission sources of PM(2.5) responsible for adverse health effects of cardiovascular function are unclear. Spontaneously hypertensive rats were implemented with radiotelemeters to record ECG responses during inhalation exposure to concentrated ambient particles (CAPs) for 13 consecutive days in Steubenville, OH. Changes in heart rate (HR) and its variability (HRV) were compared to PM(2.5) trace elements in 30-min time frames to capture acute physiological responses with real-time fluctuations in PM(2.5) composition. Using positive matrix factorization, six major source factors were identified: (i) coal/secondary, (ii) mobile sources, (iii) metal coating/processing, (iv) iron/steel manufacturing, (v) lead and (vi) incineration. Exposure-related changes in HR and HRV were dependant on winds predominately from either the northeast (NE) or southwest (SW). During SW winds, the metal processing factor was associated with increased HR, whereas factors of incineration, lead and iron/steel with NE winds were associated with decreased HR. Decreased SDNN was dominated during NE winds by the incinerator factor, and with SW winds by the metal factor. Metals and mobile source factors also had minor impacts on decreased SDNN with NE winds. Individual elemental components loaded onto these factors generally showed significant associations, although there were some discrepancies. Acute cardiovascular changes in response to ambient PM(2.5) exposure can be attributed to specific PM constituents and sources linked with incineration, metal processing, and iron/steel production.

Structurally distinct polycyclic aromatic hydrocarbons induce differential transcriptional responses in developing zebrafish

PubMed Central

Goodale, Britton C.; Tilton, Susan C.; Wilson, Glenn; Corvi, Margaret M.; Janszen, Derek B.; Anderson, Kim A.; Waters, Katrina M.; Tanguay, Robert L.

2014-01-01

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. These multi-ring chemicals differentially activate the Aryl Hydrocarbon Receptor (AHR) in a structurally dependent manner, and induce toxicity via both AHR-dependent and-independent mechanisms. PAH exposure is known to induce developmental malformations in zebrafish embryos, and recent studies have shown cardiac toxicity induced by compounds with low AHR affinity. Unraveling the potentially diverse molecular mechanisms of PAH toxicity is essential for understanding the hazard posed by complex PAH mixtures present in the environment. We analyzed transcriptional responses to PAH exposure in zebrafish embryos exposed to benz(a)anthracene (BAA), dibenzothiophene (DBT) and pyrene (PYR) at concentrations that induced developmental malformations by 120 hours post-fertilization (hpf). Whole genome microarray analysis of mRNA expression at 24 and 48 hpf identified genes that were differentially regulated over time and in response to the three PAH structures. PAH body burdens were analyzed at both time points using GC-MS, and demonstrated differences in PAH uptake into the embryos. This was important for discerning dose-related differences from those that represented unique molecular mechanisms. While BAA misregulated the least number of transcripts, it caused strong induction of cyp1a and other genes known to be downstream of the AHR, which were not induced by the other two PAHs. Analysis of functional roles of misregulated genes and their predicted regulatory transcription factors also distinguished the BAA response from regulatory networks disrupted by DBT and PYR exposure. These results indicate that systems approaches can be used to classify the toxicity of PAHs based on the networks perturbed following exposure, and may provide a path for unraveling the toxicity of complex PAH mixtures. PMID:23656968

Plasmonic resonances of nanoparticles from large-scale quantum mechanical simulations

NASA Astrophysics Data System (ADS)

Zhang, Xu; Xiang, Hongping; Zhang, Mingliang; Lu, Gang

2017-09-01

Plasmonic resonance of metallic nanoparticles results from coherent motion of its conduction electrons, driven by incident light. For the nanoparticles less than 10 nm in diameter, localized surface plasmonic resonances become sensitive to the quantum nature of the conduction electrons. Unfortunately, quantum mechanical simulations based on time-dependent Kohn-Sham density functional theory are computationally too expensive to tackle metal particles larger than 2 nm. Herein, we introduce the recently developed time-dependent orbital-free density functional theory (TD-OFDFT) approach which enables large-scale quantum mechanical simulations of plasmonic responses of metallic nanostructures. Using TD-OFDFT, we have performed quantum mechanical simulations to understand size-dependent plasmonic response of Na nanoparticles and plasmonic responses in Na nanoparticle dimers and trimers. An outlook of future development of the TD-OFDFT method is also presented.

Depolarization- and transmitter-induced changes in intracellular Ca2+ of rat cerebellar granule cells in explant cultures.

PubMed

Connor, J A; Tseng, H Y; Hockberger, P E

1987-05-01

Digital imaging of the Ca indicator fura-2 has been used to study the responses of developing granule cells in culture to depolarization and transmitter action. Unstimulated cells bathed in Krebs saline exhibited cytoplasmic Ca ion concentrations, [Ca2+], that were generally in the 30-60 nM range. Exposure of cells to high-potassium (25 mM) saline depolarized the membrane potential and produced an immediate rise in [Ca2+] that recovered within 2-3 min in normal saline. The response grew progressively larger over the first 20 d in culture. Transient increases in [Ca2+] to levels greater than 1 microM were observed after 12-14 d in vitro, at which time the cells displayed intense electrical activity when exposed to high K. At this stage, the increases were attenuated by blocking action potential activity with TTX. In TTX-treated or immature cells, in which the transient phase of the Ca change was relatively small, a second exposure to high K typically produced a much larger Ca response that the initial exposure. The duration of this facilitation of the response persisted for periods longer than 5 min. Application of the neurotransmitter GABA induced a transient increase in membrane conductance, with a reversal potential near resting potential (approx. -60 mV), and caused an intracellular Ca2+ increase that outlasted the exposure to GABA by several minutes. Glutamate, or kainate, induced an increase in membrane conductance but with a reversal potential more positive than spike threshold. These agents also elevated intracellular Ca2+, but unlike the case with GABA, this Ca response reversed rapidly upon removal of the transmitter. The facilitatory effect of repeated exposures to high-K saline, as well as the persistent Ca elevation following a brief GABA application, suggests that granule cells possess the capability of displaying activity-dependent changes in Ca levels in culture.

T CELLS LOCALIZED TO THE ANDROGEN-DEPRIVED PROSTATE ARE TH1 AND TH17 BIASED

PubMed Central

Morse, Matthew D.; McNeel, Douglas G.

2013-01-01

BACKGROUND T cells infiltrate the prostates of prostate cancer patients undergoing neoadjuvant androgen deprivation. These prostate-infiltrating T cells have an oligoclonal phenotype, suggesting the development of an antigen-specific T-cell response. We hypothesized that androgen deprivation might elicit a prostate tissue-specific T-cell response that could potentially be combined with other immune-active therapies, and consequently sought to investigate the nature and timing of this T-cell response following castration. METHODS We investigated the phenotype and cytokine expression of T cells at various time points in the prostates of Lewis rats following surgical castration, and used adoptive transfer of prostate-infiltrating lymphocytes to determine whether the infiltration by T cells was mediated by effects of castration on the prostate or lymphocytes. RESULTS Prostate T-cell infiltration shortly after castration was TH1 biased up to approximately 30 days, followed by a predominance of TH17-type cells, which persisted until at least 90 days post castration. Prostate-infiltrating lymphocytes from sham-treated or castrate rats localized to the prostates of castrate animals. CONCLUSIONS These observations suggest castration elicits a time-dependent prostate-specific T-cell infiltration, and this infiltration is likely mediated by effects of castration on prostate tissue rather than T cells. These findings have implications for the timing of immunotherapies combined with androgen deprivation as treatments for prostate cancer. PMID:22213030

Eulerian velocity reconstruction in ideal atmospheric dynamics using potential vorticity and potential temperature

NASA Astrophysics Data System (ADS)

Blender, R.

2009-04-01

An approach for the reconstruction of atmospheric flow is presented which uses space- and time-dependent fields of density ?, potential vorticity Q and potential temperature Î& cedil;[J. Phys. A, 38, 6419 (2005)]. The method is based on the fundamental equations without approximation. The basic idea is to consider the time-dependent continuity equation as a condition for zero divergence of momentum in four dimensions (time and space, with unit velocity in time). This continuity equation is solved by an ansatz for the four-dimensional momentum using three conserved stream functions, the potential vorticity, potential temperature and a third field, denoted as ?-potential. In zonal flows, the ?-potential identifies the initial longitude of particles, whereas potential vorticity and potential temperature identify mainly meridional and vertical positions. Since the Lagrangian tracers Q, Î&,cedil; and ? determine the Eulerian velocity field, the reconstruction combines the Eulerian and the Lagrangian view of hydrodynamics. In stationary flows, the ?-potential is related to the Bernoulli function. The approach requires that the gradients of the potential vorticity and potential temperature do not vanish when the velocity remains finite. This behavior indicates a possible interrelation with stability conditions. Examples with analytical solutions are presented for a Rossby wave and zonal and rotational shear flows.

76 FR 32358 - Open Meeting Notice; Advisory Council on Dependents' Education

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

...' Education AGENCY: Department of Defense Education Activity (DoDEA), DoD. ACTION: Open meeting notice... on Dependents' Education will take place. DATES: Friday, September 23, 2011, Japan Standard Time at...' Education about its mission and functions. Written statements may be submitted at any time or in response to...

Student understanding of time dependence in quantum mechanics

NASA Astrophysics Data System (ADS)

Emigh, Paul J.; Passante, Gina; Shaffer, Peter S.

2015-12-01

[This paper is part of the Focused Collection on Upper Division Physics Courses.] The time evolution of quantum states is arguably one of the more difficult ideas in quantum mechanics. In this article, we report on results from an investigation of student understanding of this topic after lecture instruction. We demonstrate specific problems that students have in applying time dependence to quantum systems and in recognizing the key role of the energy eigenbasis in determining the time dependence of wave functions. Through analysis of student responses to a set of four interrelated tasks, we categorize some of the difficulties that underlie common errors. The conceptual and reasoning difficulties that have been identified are illustrated through student responses to four sets of questions administered at different points in a junior-level course on quantum mechanics. Evidence is also given that the problems persist throughout undergraduate instruction and into the graduate level.

Effect of the δ-potential on spin-dependent electron tunneling in double barrier semiconductor heterostructure

NASA Astrophysics Data System (ADS)

Chandrasekar, L. Bruno; Gnanasekar, K.; Karunakaran, M.

2018-06-01

The effect of δ-potential was studied in GaAs/Ga0.6Al0·4As double barrier heterostructure with Dresselhaus spin-orbit interaction. The role of barrier height and position of the δ- potential in the well region was analysed on spin-dependent electron tunneling using transfer matrix method. The spin-separation between spin-resonances on energy scale depends on both height and position of the δ- potential, whereas the tunneling life time of electrons highly influenced by the position of the δ- potential and not on the height. These results might be helpful for the fabrication of spin-filters.

Particulate metal bioaccessibility in physiological fluids and cell culture media: Toxicological perspectives.

PubMed

Leclercq, Bérénice; Alleman, Laurent Yves; Perdrix, Esperanza; Riffault, Véronique; Happillon, Mélanie; Strecker, Alain; Lo-Guidice, Jean-Marc; Garçon, Guillaume; Coddeville, Patrice

2017-07-01

According to the literature, tiny amounts of transition metals in airborne fine particles (PM 2.5 ) may induce proinflammatory cell response through reactive oxygen species production. The solubility of particle-bound metals in physiological fluids, i.e. the metal bioaccessibility is driven by factors such as the solution chemical composition, the contact time with the particles, and the solid-to-liquid phase ratio (S/L). In this work, PM 2.5 -bound metal bioaccessibility was assessed in various physiological-like solutions including cell culture media in order to evidence the potential impact on normal human bronchial epithelial cells (NHBE) when studying the cytotoxicity and inflammatory responses of PM 2.5 towards the target bronchial compartment. Different fluids (H 2 O, PBS, LHC-9 culture medium, Gamble and human respiratory mucus collected from COPD patients), various S/L conditions (from 1/6000 to 1/100,000) and exposure times (6, 24 and 72h) were tested on urban PM 2.5 samples. In addition, metals' total, soluble and insoluble fractions from PM 2.5 in LHC-9 were deposited on NHBE cells (BEAS-2B) to measure their cytotoxicity and inflammatory potential (i.e., G6PDH activity, secretion of IL-6 and IL-8). The bioaccessibility is solution-dependent. A higher salinity or organic content may increase or inhibit the bioaccessibiliy according to the element, as observed in the complex mucus matrix. Decreasing the S/L ratio also affect the bioaccessibility depending on the solution tested while the exposure time appears less critical. The LHC-9 culture medium appears to be a good physiological proxy as it induces metal bioaccessibilities close to the mucus values and is little affected by S/L ratios or exposure time. Only the insoluble fraction can be linked to the PM 2.5 -induced cytotoxicity. By contrast, both soluble and insoluble fractions can be related to the secretion of cytokines. The metal bioaccessibility in LHC-9 of the total, soluble, and insoluble fractions of the PM 2.5 under study did not explain alone, the cytotoxicity nor the inflammatory response observed in BEAS-2B cells. These findings confirm the urgent need to perform further toxicological studies to better evaluate the synergistic effect of both bioaccessible particle-bound metals and organic species. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term hydrodynamic response induced by past climatic and geomorphologic forcing: The case of the Paris basin, France

NASA Astrophysics Data System (ADS)

Jost, A.; Violette, S.; Gonçalvès, J.; Ledoux, E.; Guyomard, Y.; Guillocheau, F.; Kageyama, M.; Ramstein, G.; Suc, J.-P.

In the framework of safe underground storage of radioactive waste in low-permeability layers, it is essential to evaluate the mobility of deep groundwaters over timescales of several million years. On these timescales, the environmental evolution of a repository should depend upon a range of natural processes that are primarily driven by climate and geomorphologic variations. In this paper, the response of the Paris basin groundwater system to variations in its hydrodynamic boundary conditions induced by past climate and geodynamic changes over the last five million years is investigated. A three-dimensional transient modelling of the Paris basin aquifer/aquitard system was developed using the code NEWSAM (Ecole des Mines de Paris, ENSMP). The geometry and hydrodynamic parameters of the model originate from a basin model, NEWBAS (ENSMP), built to simulate the geological history of the basin. Geomorphologic evolution is deduced from digital elevation model analysis, which allows to estimate river-valley incision and alpine surrection. Climate forcing results from palaeoclimate modelling experiments using the LMDz atmospheric general circulation model (Institut Pierre Simon Laplace) with a refined spatial resolution, for the present, the Last Glacial Maximum (21 ka) and the Middle Pliocene Warmth (˜3 Ma). The water balance is computed by the distributed hydrological model MODSUR (ENSMP). Results about the simulated evolution of piezometric heads in the system in response to the altered boundary conditions are presented, in particular in the vicinity of ANDRA’s Bure potential repository site within the Callovo-Oxfordian argillaceous layer. For the present, the comparison of head patterns between steady state and time dependent simulation shows little differences for aquifer layers close to the surface but suggests a transient state of the current system in the main aquitards of the basin and in the deep aquifers, characterized by abnormally low fluid potentials. The dependence of the boundary-induced transient effects on the hydraulic diffusivity is illustrated by means of a sensitivity study.

Speed effects of deep brain stimulation for Parkinson's disease.

PubMed

Klostermann, Fabian; Wahl, Michael; Marzinzik, Frank; Vesper, Jan; Sommer, Werner; Curio, Gabriel

2010-12-15

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) accelerates reaction time (RT) in patients with Parkinson's disease (PD), particularly in tasks in which decisions on the response side have to be made. This might indicate that DBS speeds up both motor and nonmotor operations. Therefore, we studied the extent to which modifications of different processing streams could explain changes of RT under subthalamic DBS. Ten PD patients on-DBS and off-DBS and 10 healthy subjects performed a choice-response task (CRT), requiring either right or left finger button presses. At the same time, EEG recordings were performed, so that RTs could be assessed together with lateralized readiness potentials (LRP), indicative of movement preparation. Additionally, an oddball task (OT) was run, in which right finger responses to target stimuli were recorded along with cognitive P300 responses. Generally, PD patients off-DBS had longer RTs than controls. Subthalamic DBS accelerated RT only in CRT. This could largely be explained by analog shortenings of LRP. No DBS-dependent changes were identified in OT, neither on the level of RT nor on the level of P300 latencies. It follows that RT accelerations under DBS of the STN are predominantly due to effects on the timing of motor instead of nonmotor processes. This starting point explains why DBS gains of response speed are low in tasks in which reactions are initiated from an advanced level of movement preparation (as in OT), and high whenever motor responses have to be raised from scratch (as in CRT). © 2010 Movement Disorder Society.

Allergic Potential and Immunotoxicity Induced by Topical Application of 1-Chloro-4-(Trifluoromethyl)Benzene (PCBTF) in a Murine Model

PubMed Central

Franko, Jennifer; Jackson, Laurel G.; Meade, B. Jean; Anderson, Stacey E.

2011-01-01

The purpose of the studies in this paper was to evaluate the allergic potential, immunotoxicity, and irritancy of the occupationally relevant chemical, 1-chloro-4-(trifluoromethyl)benzene, also known as parachlorobenzotrifluoride (PCBTF), following dermal exposure in a murine model. Evaluation of the sensitization potential, conducted using the local lymph node assay (LLNA) at concentrations ranging from 50% to 100%, identified a dose-dependent increase in lymphocyte proliferation with a calculated EC3 value of 53.1%. While no elevations in total or specific IgE were observed after exposure to any concentration of the chemical, significant increases in IFN-γ protein production by stimulated draining lymphoid cells were observed, indicating a T-cell-mediated response. Dermal exposure to PCBTF was not found to alter the immune response to a T-cell-dependant antigen. These results demonstrate that PCBTF has the potential to induce allergic sensitization following dermal exposure and based on LLNA results would be classified as a weak sensitizer. PMID:21747864

Modelling and simulation of biased agonism dynamics at a G protein-coupled receptor.

PubMed

Bridge, L J; Mead, J; Frattini, E; Winfield, I; Ladds, G

2018-04-07

Theoretical models of G protein-coupled receptor (GPCR) concentration-response relationships often assume an agonist producing a single functional response via a single active state of the receptor. These models have largely been analysed assuming steady-state conditions. There is now much experimental evidence to suggest that many GPCRs can exist in multiple receptor conformations and elicit numerous functional responses, with ligands having the potential to activate different signalling pathways to varying extents-a concept referred to as biased agonism, functional selectivity or pluri-dimensional efficacy. Moreover, recent experimental results indicate a clear possibility for time-dependent bias, whereby an agonist's bias with respect to different pathways may vary dynamically. Efforts towards understanding the implications of temporal bias by characterising and quantifying ligand effects on multiple pathways will clearly be aided by extending current equilibrium binding and biased activation models to include G protein activation dynamics. Here, we present a new model of time-dependent biased agonism, based on ordinary differential equations for multiple cubic ternary complex activation models with G protein cycle dynamics. This model allows simulation and analysis of multi-pathway activation bias dynamics at a single receptor for the first time, at the level of active G protein (α GTP ), towards the analysis of dynamic functional responses. The model is generally applicable to systems with N G G proteins and N* active receptor states. Numerical simulations for N G =N * =2 reveal new insights into the effects of system parameters (including cooperativities, and ligand and receptor concentrations) on bias dynamics, highlighting new phenomena including the dynamic inter-conversion of bias direction. Further, we fit this model to 'wet' experimental data for two competing G proteins (G i and G s ) that become activated upon stimulation of the adenosine A 1 receptor with adenosine derivative compounds. Finally, we show that our model can qualitatively describe the temporal dynamics of this competing G protein activation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Expression of stress response HSP70 gene in Asian paddle crabs, Charybdis japonica, exposure to endocrine disrupting chemicals, bisphenol A (BPA) and 4-nonylphenol (NP)

NASA Astrophysics Data System (ADS)

Park, Kiyun; Kwak, Ihn-Sil

2013-06-01

The Asian paddle crab, Charybdis japonica, is a potential bio-indicator reflecting marine sediment toxicity as well as a commercially important species living along coastal areas in Korea. This study investigated its stress response by looking at the heat shock protein (HSP70) gene of C. japonica when the organism is exposed to bisphenol A (BPA) and 4-nonylphenol (NP). We characterized partial sequence of HSP70 as the stressresponse gene of C. japonica. The nucleotide sequence of C. japonica HSP70 is over 90% homologous with the corresponding gene of other crabs. Phylogenetic tree analysis revealed a close relationship between C. japonica HSP70 and HSP70 in other species of lobster and shrimps. HSP70 mRNA transcripts were detected in all the examined tissues of C. japonica, with the highest level in gills, the organ that most frequently came into contact with the external BPA or NP-laden water. As no reference data were available for C. japonica crab exposure, the BPA and NP 24-h LC50 values have not been previously determined. The expression of the C. japonica HSP70 gene to various BPA or NP concentrations during short and longer times was assessed. Gene expression was significantly induced in concentration- and time-dependent manners after BPA or NP exposures. These results support the postulation that crab C. japonica HSP70 could be a potential stress response molecular marker to monitor marine ecosystems.

Modeling ultrafast solvated electronic dynamics using time-dependent density functional theory and polarizable continuum model.

PubMed

Liang, Wenkel; Chapman, Craig T; Ding, Feizhi; Li, Xiaosong

2012-03-01

A first-principles solvated electronic dynamics method is introduced. Solvent electronic degrees of freedom are coupled to the time-dependent electronic density of a solute molecule by means of the implicit reaction field method, and the entire electronic system is propagated in time. This real-time time-dependent approach, incorporating the polarizable continuum solvation model, is shown to be very effective in describing the dynamical solvation effect in the charge transfer process and yields a consistent absorption spectrum in comparison to the conventional linear response results in solution. © 2012 American Chemical Society

Responsive systems - The challenge for the nineties

NASA Technical Reports Server (NTRS)

Malek, Miroslaw

1990-01-01

A concept of responsive computer systems will be introduced. The emerging responsive systems demand fault-tolerant and real-time performance in parallel and distributed computing environments. The design methodologies for fault-tolerant, real time and responsive systems will be presented. Novel techniques of introducing redundancy for improved performance and dependability will be illustrated. The methods of system responsiveness evaluation will be proposed. The issues of determinism, closed and open systems will also be discussed from the perspective of responsive systems design.

Climate sensitivity, sea level and atmospheric carbon dioxide

PubMed Central

Hansen, James; Sato, Makiko; Russell, Gary; Kharecha, Pushker

2013-01-01

Cenozoic temperature, sea level and CO2 covariations provide insights into climate sensitivity to external forcings and sea-level sensitivity to climate change. Climate sensitivity depends on the initial climate state, but potentially can be accurately inferred from precise palaeoclimate data. Pleistocene climate oscillations yield a fast-feedback climate sensitivity of 3±1°C for a 4 W m−2 CO2 forcing if Holocene warming relative to the Last Glacial Maximum (LGM) is used as calibration, but the error (uncertainty) is substantial and partly subjective because of poorly defined LGM global temperature and possible human influences in the Holocene. Glacial-to-interglacial climate change leading to the prior (Eemian) interglacial is less ambiguous and implies a sensitivity in the upper part of the above range, i.e. 3–4°C for a 4 W m−2 CO2 forcing. Slow feedbacks, especially change of ice sheet size and atmospheric CO2, amplify the total Earth system sensitivity by an amount that depends on the time scale considered. Ice sheet response time is poorly defined, but we show that the slow response and hysteresis in prevailing ice sheet models are exaggerated. We use a global model, simplified to essential processes, to investigate state dependence of climate sensitivity, finding an increased sensitivity towards warmer climates, as low cloud cover is diminished and increased water vapour elevates the tropopause. Burning all fossil fuels, we conclude, would make most of the planet uninhabitable by humans, thus calling into question strategies that emphasize adaptation to climate change. PMID:24043864

Climate sensitivity, sea level and atmospheric carbon dioxide.

PubMed

Hansen, James; Sato, Makiko; Russell, Gary; Kharecha, Pushker

2013-10-28

Cenozoic temperature, sea level and CO2 covariations provide insights into climate sensitivity to external forcings and sea-level sensitivity to climate change. Climate sensitivity depends on the initial climate state, but potentially can be accurately inferred from precise palaeoclimate data. Pleistocene climate oscillations yield a fast-feedback climate sensitivity of 3±1(°)C for a 4 W m(-2) CO2 forcing if Holocene warming relative to the Last Glacial Maximum (LGM) is used as calibration, but the error (uncertainty) is substantial and partly subjective because of poorly defined LGM global temperature and possible human influences in the Holocene. Glacial-to-interglacial climate change leading to the prior (Eemian) interglacial is less ambiguous and implies a sensitivity in the upper part of the above range, i.e. 3-4(°)C for a 4 W m(-2) CO2 forcing. Slow feedbacks, especially change of ice sheet size and atmospheric CO2, amplify the total Earth system sensitivity by an amount that depends on the time scale considered. Ice sheet response time is poorly defined, but we show that the slow response and hysteresis in prevailing ice sheet models are exaggerated. We use a global model, simplified to essential processes, to investigate state dependence of climate sensitivity, finding an increased sensitivity towards warmer climates, as low cloud cover is diminished and increased water vapour elevates the tropopause. Burning all fossil fuels, we conclude, would make most of the planet uninhabitable by humans, thus calling into question strategies that emphasize adaptation to climate change.

Lactic acid bacteria and bifidobacteria attenuate the proinflammatory response in intestinal epithelial cells induced by Salmonella enterica serovar Typhimurium.

PubMed

Carey, Christine M; Kostrzynska, Magdalena

2013-01-01

Inflammation is a physiological response to infections and tissue injury; however, abnormal immune responses can give rise to chronic inflammation and contribute to disease progression. Various dietary components, including probiotic lactic acid bacteria and prebiotics, have the potential to modulate intestinal inflammatory responses. One factor in particular, the chemokine interleukin-8 (IL-8, CXCL-8), is one of the major mediators of the inflammatory response. The purpose of this study was to investigate modulation of the inflammatory host response induced by Salmonella enterica serovar Typhimurium DT104 in the presence of selected probiotics and lactic acid bacteria (LAB) isolated from human sources, dairy products, and farm animals. IL-8 gene expression and protein production in HT-29 cells were evaluated by real-time PCR and ELISA, respectively. Pre-incubation of HT-29 cells with Lactobacillus kefir IM002, Bifidobacterium adolescentis FRP 61, Bifidobacterium longum FRP 68 and FRP 69, Bifidobacterium breve FRP 334, and Leuconostoc mesenteroides IM080 significantly inhibited IL-8 secretion induced by Salmonella Typhimurium DT104. Co-culture of selected probiotics and Salmonella Typhimurium DT104 reduced IL-8 production, while potential probiotics and LAB had no effect on IL-8 secretion in HT-29 cells preincubated with Salmonella Typhimurium DT104 prior to adding probiotics. Lactobacillus kefir IM002 supernatant also significantly reduced IL-8 production. In conclusion, our study suggests that probiotic bifidobacteria and LAB modulate cytokine induction and possess anti-inflammatory properties; however, the effectiveness is strain dependent.

Strychnine blocks transient but not sustained inhibition in mudpuppy retinal ganglion cells.

PubMed Central

Belgum, J H; Dvorak, D R; McReynolds, J S

1984-01-01

Transient and sustained inhibitory synaptic inputs to on-centre, off-centre, and on-off ganglion cells in the mudpuppy retina were studied using intracellular recording in the superfused eye-cup preparation. When chemical transmission was blocked with 4 mM-Co2+, application of either glycine or gamma-aminobutyric acid (GABA) caused a hyperpolarization and conductance increase in all ganglion cells. For both amino acids, the responses were dose dependent in the range 0.05-10 mM, with a half-maximal response at about 0.7 mM. Glycine and GABA sensitivities were very similar in all three types of ganglion cells. The response to applied glycine was selectively antagonized by 10(-5) M-strychnine and the response to applied GABA was selectively antagonized by 10(-5) M-picrotoxin. In all ganglion cells, 10(-5) M-strychnine eliminated the transient inhibitory events which occur at the onset and termination of a light stimulus. The block of transient inhibition was associated with a relative depolarization of membrane potential and decrease in conductance at these times. Strychnine had no effect on membrane potential or conductance in darkness or during sustained inhibitory responses to light. Picrotoxin (10(-5) M) did not block transient inhibitory events in any ganglion cells, but did affect other components of their responses. The results suggest that in all three classes of ganglion cells transient inhibition, but not sustained inhibition, may be mediated by glycine or a closely related substance. PMID:6481635

The electrostatics of solvent and membrane interfaces and the role of electronic polarizability

NASA Astrophysics Data System (ADS)

Vorobyov, Igor; Allen, Toby W.

2010-05-01

The electrostatics of solvent and lipid bilayer interfaces are investigated with the aim of understanding the interaction of ions and charged peptides with biological membranes. We overcome the lacking dielectric response of hydrocarbon by carrying out atomistic molecular dynamics simulations using a polarizable model. For air-solvent or solvent-solvent interfaces, the effect of polarizability itself is small, yet changes in the fixed atomic charge distribution are responsible for substantial changes in the potential. However, when electrostatics is probed by finite solutes, a cancellation of dominant quadrupolar terms from the macroscopic and microscopic (solute-solvent) interfaces eliminates this dependence and leads to small net contributions to partitioning thermodynamics. In contrast, the membrane dipole potential exhibits considerable dependence on lipid electronic polarizability, due to its dominant dipolar contribution. We report the dipole potential for a polarizable lipid hydrocarbon membrane model of 480-610 mV, in better accord with experimental measurements.

The evolution of the major hepatitis C genotypes correlates with clinical response to interferon therapy.

PubMed

Pang, Phillip S; Planet, Paul J; Glenn, Jeffrey S

2009-08-11

Patients chronically infected with hepatitis C virus (HCV) require significantly different durations of therapy and achieve substantially different sustained virologic response rates to interferon-based therapies, depending on the HCV genotype with which they are infected. There currently exists no systematic framework that explains these genotype-specific response rates. Since humans are the only known natural hosts for HCV-a virus that is at least hundreds of years old-one possibility is that over the time frame of this relationship, HCV accumulated adaptive mutations that confer increasing resistance to the human immune system. Given that interferon therapy functions by triggering an immune response, we hypothesized that clinical response rates are a reflection of viral evolutionary adaptations to the immune system. We have performed the first phylogenetic analysis to include all available full-length HCV genomic sequences (n = 345). This resulted in a new cladogram of HCV. This tree establishes for the first time the relative evolutionary ages of the major HCV genotypes. The outcome data from prospective clinical trials that studied interferon and ribavirin therapy was then mapped onto this new tree. This mapping revealed a correlation between genotype-specific responses to therapy and respective genotype age. This correlation allows us to predict that genotypes 5 and 6, for which there currently are no published prospective trials, will likely have intermediate response rates, similar to genotype 3. Ancestral protein sequence reconstruction was also performed, which identified the HCV proteins E2 and NS5A as potential determinants of genotype-specific clinical outcome. Biochemical studies have independently identified these same two proteins as having genotype-specific abilities to inhibit the innate immune factor double-stranded RNA-dependent protein kinase (PKR). An evolutionary analysis of all available HCV genomes supports the hypothesis that immune selection was a significant driving force in the divergence of the major HCV genotypes and that viral factors that acquired the ability to inhibit the immune response may play a role in determining genotype-specific response rates to interferon therapy.